Fluid Management

Platelet-Dependent Inflammatory Dysregulation in Patients with Stages 4 or 5 Chronic Kidney Disease: A Mechanistic Clinical Study

Corken, Adam — Wed, 26 Oct 2022 02:03:07 GMT-07:00

Healthcare resource utilization and costs of persistent severe AKI among hospitalized Stage 2/3 AKI patients

Rachel_Mackey@premierinc.com — Sun, 18 Dec 2022 09:38:34 GMT-08:00

Background: Persistent severe acute kidney injury (PS-AKI) is associated with worse clinical outcomes, but there is no data on costs of PS-AKI. We compared costs and healthcare resource utilization (HRU) for inpatients with PS-AKI vs. not-persistent severe AKI (NPS-AKI) overall and by ICU use. Methods: This retrospective observational study included 126,528 adult US inpatients in the PINC AI Healthcare Database (PHD), discharged from January 1, 2017, to December 31, 2019, with KDIGO stage 2 or 3 AKI (by serum creatinine [SCr] criteria) during hospitalization, length of stay (LOS) ≥3 days, and ≥3 SCr measurements. Patients were categorized as PS-AKI (defined as stage 3 AKI lasting ≥3 days or with death within 3 days or stage 2/3 AKI (by SCr criteria) with dialysis within 3 days), or NPS-AKI. Generalized linear model regression compared LOS and costs during index hospitalization (total cohort) and 30-days post-discharge (survivors of index hospitalization), adjusted for patient, hospital, and clinical characteristics. Results: Among 126,528 patients with stage 2/3 AKI, 30,916 developed PS-AKI. In adjusted models, compared to NPS-AKI, patients with PS-AKI had 32% longer total LOS (+3.3 days), 45% longer ICU LOS (+ 2.6 days), 46% higher total costs (+$13,143), 58% higher ICU costs (+$15,908), and during 30-days post-discharge, had 13% longer readmission LOS (+1.0 day), 22% higher readmission costs (+$4049), and 12% higher outpatient costs (+$206) (p<0.005 for all). Relative LOS and cost differences for PS-AKI vs. NPS-AKI were similar for ICU (n=57,947) and non-ICU (n=68,581) patients. Conclusions: Among hospitalized stage 2/3 AKI patients, PS-AKI was associated with significantly longer LOS and higher costs during index hospitalization and 30-days post-discharge, overall, and in ICU and non-ICU patients. Preventing PS-AKI among patients with stage 2/3 AKI may reduce hospital LOS and costs.

Zinc Deficiency: Potential Hidden Driver of the Detrimental Cycle of Chronic Kidney Disease and Hypertension

clintoria.williams@wright.edu — Sun, 18 Dec 2022 09:38:34 GMT-08:00

Globally, over 103 million individuals are afflicted by chronic kidney disease (CKD), a silent killer claiming the lives of 1.2 million people annually. CKD is characterized by 5 progressive stages, in which dialysis and kidney transplant are life-saving routes for patients with end-stage kidney failure. While kidney damage impairs kidney function and derails blood pressure regulation, uncontrolled hypertension accelerates the development and progression of CKD. Zinc (Zn) deficiency has emerged as a potential hidden driver within this detrimental cycle of CKD and hypertension. This review article will 1) highlight mechanisms of Zn procurement and trafficking, 2) provide evidence that urinary Zn wasting can fuel Zn deficiency in CKD, 3) discuss how Zn deficiency can accelerate the progression of hypertension and kidney damage in CKD, and 4) consider Zn supplementation as an exit strategy with the potential to rectify the course of hypertension and CKD progression.

Current Status of Renal Xenotransplantation and Next Steps

ajt135@miami.edu — Sun, 18 Dec 2022 09:38:34 GMT-08:00

Renal transplantation is the preferred treatment of ESRD, but the shortage of suitable donor kidneys from the cadaver pool means that many patients with ESRD will not receive a kidney transplant. Xenotransplantation has long represented a solution to the kidney shortage, but the occurrence of antibody-mediated rejection has precluded its clinical development. Developments in: somatic cell nuclear transfer in pigs, gene editing tools have led to the creation of new donor pigs with greatly improved crossmatches to patients. In addition, improvements in preclinical kidney xenotransplant survival using new anti-CD40/CD154 based immunosuppression, have pushed xenotransplantation to the point where it is reasonable to consider initiating a clinical trial to evaluate this potential therapy in patients.

Risk and Timing of De Novo Sepsis in Critically Ill Children Following Acute Kidney Injury

cle34@pitt.edu — Sun, 18 Dec 2022 09:38:34 GMT-08:00

Background: Acute kidney injury (AKI) is common among critically ill children and is associated with an increased risk for de novo infection, however little is known about the epidemiology and temporal relationship between AKI and AKI-associated infection in this cohort. Methods: We conducted a single-center retrospective cohort study of children admitted to the pediatric and cardiac ICUs at a tertiary pediatric care center. The relationship between non-septic AKI and the development of hospital-acquired sepsis was assessed using Cox proportional-hazards models using AKI as a time-varying covariate. Results: Among the 5695 children included in the study, AKI occurred in 20.2% from ICU admission through 30 days. Hospital-acquired sepsis occurred twice as often among children with AKI compared to those without AKI (10.1% vs. 4.6%) with an adjusted hazard ratio of 1.42 (95% CI 1.12-1.81). Among the 117 children who developed sepsis following AKI, 80.3% developed sepsis within 7 days and 96.6% within 14 days of AKI onset, with a median time from AKI onset to sepsis of 2.6 days (IQR 1.5-4.7). When assessing change in risk over time, the hazard rate for sepsis remained elevated for children with stage 3 AKI compared to children without AKI at 13.5 days following AKI onset, after which the estimation of hazard rates was limited by the number of children remaining in the hospital. Conclusions: AKI is an independent risk factor for de novo sepsis. Critically ill children with stage 3 AKI remain at increased risk for sepsis at 13.5 days following AKI onset.

Sex and Racial/Ethnic Differences in Home Hemodialysis Mortality

shah2sv@ucmail.uc.edu — Sun, 18 Dec 2022 08:41:27 GMT-08:00

Background: Women and minorities constitute substantial portions of the prevalent population of kidney failure patients. Little is known about sex and racial/ethnic differences in mortality among patients with kidney failure on home hemodialysis in the United States. Methods: Using the United States Renal Data System, we retrospectively evaluated a cohort of 42,849 patients who started home hemodialysis between January 1, 2005, and December 31, 2015. We examined the association of sex and race/ethnicity with the outcome of all-cause mortality using adjusted Cox proportional hazard models and logistic regression models. Results: In the study cohort, 40.4% were women, and 57.4% were White. Women on home hemodialysis had higher unadjusted death rates (26.9 vs. 22.4 per 100 person-years) as compared to men. There was no difference in adjusted all-cause mortality between men and women, but women had an 8% higher adjusted risk of all-cause mortality at one-year after initiating home hemodialysis (OR 1.08, 1.01-1.15). With regards to race/ethnicity, Hispanic, White, and Blacks had higher unadjusted death rates as compared to Asians and Native Americans (25.1 vs. 24.8 vs. 23.2 vs. 17.4 vs.16.6 per 100 person-years). There was no difference in adjusted all-cause mortality in Black, Hispanic, and Native Americans as compared to Whites, while Asians had a lower risk of all-cause mortality than did Whites (HR, 0.81; CI, 0.72-0.92). There was no difference in adjusted one-year mortality for Asian, Black, Hispanic, and Native American patients, as compared to White patients. Conclusion: Among patients undergoing home hemodialysis, women have higher one-year mortality than men, and women and men have comparable survival on long-term follow-up after adjusting for other covariates. Compared to Whites, there was no difference in adjusted survival on long-term follow-up for Blacks, Hispanics, or Native Americans, while Asians had better survival. Our results suggest the need for population-wide strategies to overcome differences in home hemodialysis care.

Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKD

tor.biering@gmail.com — Sun, 18 Dec 2022 08:41:27 GMT-08:00

Background: SGLT2 inhibitors, originally developed as glucose-lowering agents for treatment of type 2 diabetes, have been shown to have cardio- and kidney protective effects among chronic kidney disease (CKD) patients with and without diabetes. However, the mechanisms remain largely unknown. Methods: DECODE-CKD is an investigator-initiated, prospective, single-center, randomized, placebo-controlled trial evaluating the effects of 6 months of treatment with 10 mg of dapagliflozin compared with placebo on cardiac structure and function in 222 adults with CKD. The primary objective is to assess whether dapagliflozin improves LV mass index. Secondary and exploratory endpoints include changes in cardiac- and kidney markers, quality of life, depressive symptoms, and cognitive function. Conclusions: This is the first study to address the effects of SGLT2 inhibitors on cardiac structure and function in patients with CKD. The results will provide valuable insights into the mechanisms underlying the cardioprotective benefits of SGLT2 inhibitors in patients with CKD.

Extracellular Vesicles in Kidney Diseases: Moving Forward

ue2u@virginia.edu — Sun, 18 Dec 2022 03:21:19 GMT-08:00

Extracellular vesicles (EVs) are evolving as novel cell mediators, biomarkers and therapeutic targets in kidney health and disease. They are naturally deriving from cells within but also outside the kidney and carry cargo which mirrors the state of the parent cell. Thus, they are potentially more sensitive and disease specific as biomarkers and messengers in various kidney diseases. Beside their role as novel communicators within the nephron they likely communicate between different organs affected by various kidney diseases. Study of urinary EVs can help to fill current knowledge gaps in kidney diseases. However, separation and characterization are challenged by their heterogeneity in size, shape and cargo. Fortunately, more sensitive and direct EV measuring tools are in development. Many clinical syndromes in nephrology from acute to chronic kidney and glomerular to tubular diseases have been studied. Yet validation of biomarkers in larger cohorts is warranted and simpler tools are needed. Translation from in vitro to in vivo studies is also urgently needed. The therapeutic role of urinary EVs in kidney diseases has been studied extensively in rodent models of AKI. Based on the current exponential growth of EV research the field of EV diagnostics and therapeutics is moving forward.

Incremental Peritoneal Dialysis - Definition, Prescription and Clinical Outcomes

adrianafernandes@campus.ul.pt — Sun, 18 Dec 2022 03:21:19 GMT-08:00

Incremental peritoneal dialysis (IPD) is a strategy of renal replacement therapy that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and lesser plastic waste and water consumption. It has also been addressed the potential benefits for RKF preservation and the lower risk of peritonitis. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF; lower clearance of medium-sized molecules (such as beta-2-microglobulin) which mostly depends on the total PD dwell time; and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate to low quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to discuss the definition and strategies to IPD prescription, as well as its advantages and disadvantages. It'll also be reviewed the current evidence regarding this strategy.

COVID-19 Vaccination and new onset glomerular disease: Results from the IRocGN2 International registry

waldmanm@niddk.nih.gov — Fri, 16 Dec 2022 03:21:56 GMT-08:00

Background:Cases of de novo glomerular disease with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established and the long-term outcomes are not known. To better characterize the glomerular diseases and clinical course/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis (IRocGN2) to study in aggregate de novo glomerulonephritis cases suspected after COVID-19 vaccine exposure Methods:A RedCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and glomerular disease histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes. Results: Ninety-eight glomerular disease cases were entered into the registry over eleven months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most the common kidney diseases reported. Recovery of kidney function and remission of proteinuria was more likely in IgAN and MCD at 4-6 months than with pauci immune glomerulonephritis /vasculitis and membranous nephropathy. Conclusions:Development of glomerular disease after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment is recommended based on these findings.

Maintenance of Remission and Risk of Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Kidney Involvement

fervenza.fernando@mayo.edu — Fri, 16 Dec 2022 10:16:52 GMT-08:00

Background. Optimal strategy for remission-maintenance therapy in patients with MPO-ANCA associated vasculitis is not established. Defining parameters to guide maintenance therapy is required. Methods. A retrospective cohort study of all patients with MPO-ANCA associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and glomerulonephritis (GN) followed at the Mayo Clinic between 1996-2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan Meier method and Cox proportional hazards regression models were applied. Results. We analyzed 159 patients with active MPO-ANCA associated vasculitis with glomerulonephritis. Sixty-six (42%) patients had at least 1 relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (HR 0.03, [95%CI, 0.002- 0.431], p=0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR 1.91, [95%CI, 1.109 - 3.293], p=0.020). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission-induction or in patients with persistently MPO-ANCA positive (OR 0.44, [95%CI,0.228-0.861], p=0.02; OR 0.42, [95%CI,0.213-0.820], p=0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% vs. 39%, p=0.49) irrespective of remission maintenance treatment. Ear nose an and throat involvement (OR 6.10 [95%CI, 1.280-29.010], p=0.02) and MPO-ANCA reappearance (OR 9.25, [95%CI, 3.126-27.361], p<0.001), were independent associated with relapse after treatment withdrawal. Conclusions. Patients persistently MPO-ANCA negative are at low risk for relapse even without remission maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with an increased risk of relapse. Serial MPO-ANCA determinations can inform the development of remission-maintenance strategies in patients with MPO-ANCA associated vasculitis with glomerulonephritis.

HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target Genes

soeren.lienkamp@anatomy.uzh.ch — Thu, 15 Dec 2022 11:34:35 GMT-08:00

Background: Hepatocyte nuclear factor 1-beta (HNF1B) is an essential transcription factor during embryogenesis. Mutations in HNF1B are the most common monogenic causes of congenital cystic dysplastic renal malformations. The direct functional consequences of mutations in HNF1B on its transcriptional activity are unknown. Methods: Direct reprogramming of mouse fibroblasts to induced renal tubular epithelial cells (iRECs) was conducted both with wild type HNF1B and with patient mutations. HNF1B was expressed in Xenopus ectodermal explants. Transcriptomic analysis by bulk RNA-Seq identified conserved targets with differentially regulated expression by the wild type or theR295C mutant. CRISPR genome editing in Xenopus embryos evaluated transcriptional targets in vivo. Results: HNF1B is essential for reprogramming mouse fibroblasts to iRECs and induces development of ectopic renal organoids from pluripotent Xenopus cells. The mutation R295C retains reprogramming and inductive capacity but alters the expression of specific sets of downstream target genes, instead of diminishing overall transcriptional activity of HNF1B. Surprisingly, targets associated with polycystic kidney disease were less affected than genes affected in congenital renal anomalies. Cross-species conserved transcriptional targets were dysregulated in hnf1b CRISPR-depleted Xenopus embryos, confirming their dependence on hnf1b. Conclusions: HNF1B activates an evolutionarily conserved program of target genes that disease-causing mutations selectively disrupt. These findings provide insights into the renal transcriptional network that controls nephrogenesis.

Tet2- and Tet3-Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron Endowment

xiujie.liang@pennmedicine.upenn.edu — Thu, 15 Dec 2022 11:34:35 GMT-08:00

Background Nephron endowment is a key determinant of hypertension and kidney disease in later life. Epigenetic changes have been proposed to mediate fetal programming and nephron number. DNA cytosine methylation, which plays a critical role in gene regulation, is affected by proteins encoded by the 10-11 translocation (TET) DNA demethylase gene family (Tet1, Tet2, and Tet3), but the roles of TET proteins in kidney development and nephron endowment have not been characterized. Methods To study whether epigenetic changes—specifically, active DNA hydroxymethylation mediated by Tet1, Tet2, and Tet3—are necessary for nephron progenitor differentiation and nephron endowment, we generated mice with deletion of Tet1, Tet2, or Tet3 in Six2-positive nephron progenitors cells (NPCs). We then performed unbiased omics profiling, including whole-genome bisulfite sequencing on isolated Six2-positive NPCs and single-cell RNA sequencing on kidneys from newborn mice. Results We did not observe changes in kidney development or function in mice with NPCspecific deletion of Tet1, Tet2, Tet3 or Tet1/Tet2 or Tet1/Tet3. On the other hand, mice with combined Tet2 and Tet3 loss in Six2-positive NPCs failed to form nephrons, leading to kidney failure and perinatal death. Tet2 and Tet3 loss in Six2-positive NPCs resulted in defective mesenchymal to epithelial transition and renal vesicle differentiation. Whole-genome bisulfite sequencing, single-cell RNA sequencing, and gene and protein expression analysis identified a defect in expression in multiple genes, including the WNT-β-catenin signaling pathway, due to a failure in demethylation of these loci in the absence of Tet2 and Tet3. Conclusions These findings suggest that Tet2- and Tet3-mediated active cytosine hydroxymethylation in NPCs play a key role in kidney development and nephron endowment.

Early Impact of the Circular Model of Kidney Allocation in the United States

puttarajappacm@upmc.edu — Thu, 27 Oct 2022 06:46:11 GMT-07:00

Background: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system based on distance from donor hospital to transplant center within/outside a 250 nautical mile radius. Impact of this policy on kidney discards and logistics is unknown. Methods: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared to a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after COVID19 onset and KAS250 implementation were evaluated using an interrupted timeseries model. Changes in allocation practices (biopsy, machine perfusion, and virtual crossmatch) were also evaluated. Results: Post-KAS250 saw a two-fold increase in kidneys imported from non-local organ procurement organizations (OPO), a higher proportion of recipients with calculated panel reactive antibody (CPRA) 81-98% (12% vs 8%, p<0.001) and those with >5 years of pre-transplant dialysis (35% vs 33%, p<0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards post-KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased while reliance on virtual crossmatch increased, which was associated with shorter CIT. Conclusion: Early trends post-KAS250 show an increase in transplant access to patients with CPRA>80 and those with longer dialysis duration, but was accompanied by an increase in CIT and a suggestion of worsening kidney discards.

Genetic determinants of interleukin-6 levels and risk of end-stage renal disease

Adriana.Hung@vumc.org — Wed, 14 Dec 2022 10:11:47 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Incidence and Risk Factors for Pruritus in Patients with Nondialysis CKD

kwulczyn@partners.org — Wed, 14 Dec 2022 09:25:33 GMT-08:00

Background: Pruritus is a common symptom experienced by patients with nondialysis CKD, but risk factors for incident pruritus in this patient population have not been evaluated. Methods: We identified 1,951 participants with CKD in the Chronic Renal Insufficiency Cohort Study without pruritus at the baseline assessment. Pruritus was assessed by the Kidney Disease Quality of Life-36 instrument, and moderate-to-severe pruritus was defined as a response of 3 or higher on a Likert scale of 1 to 5. We used time-updated multivariable joint models to evaluate the association of patient clinical characteristics, eGFR, and laboratory parameters with incident pruritus. Results: Over a median follow-up of 6 years, 660 (34%) participants developed incident moderate-to-severe pruritus, with a higher incidence rate observed among participants with more advanced CKD. In multivariable models, the hazard ratio (95% CI) for pruritus associated with a 10 mL/min/1.73 m2 lower eGFR was 1.16 (1.10 - 1.23). Older age (≥65 years), higher body mass index, diabetes, current smoking, opioid use, depressive symptoms, and serum parathyroid hormone were also associated with a higher risk of incident pruritus, while low serum calcium (<9 mg/dL) was associated with a lower risk (all p<0.05). Serum phosphate was not associated with incident pruritus in the primary analysis. Conclusions: A substantial proportion of patients with nondialysis CKD develop moderate-to-severe pruritus. While lower eGFR is associated with the risk of pruritus, other comorbidities, particularly depressive symptoms, are potential risk factors.

Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population

noraf@unc.edu — Wed, 14 Dec 2022 09:25:33 GMT-08:00

Background. Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease. Methods. We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin to creatinine ratio (UACR). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites in covariate-adjusted models that accounted for the study design. 132 metabolites were available for replication in the HyperGEN study (n = 300), and 29 metabolites were available for replication in the Malmö Offspring Study (n = 999). Results. Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-Glutamine and D-Glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. Conclusions. Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanics/Latinos.

Lived experiences of hemodialysis healthcare workers during the COVID-19 pandemic: A qualitative study from the Quebec Renal Network

marie-chantal.fortin.med@ssss.gouv.qc.ca — Tue, 13 Dec 2022 01:29:47 GMT-08:00

Background: The COVID-19 pandemic has disrupted health systems and created numerous challenges in hospitals worldwide for patients and healthcare workers (HCWs). Hemodialysis centers are at risk of COVID-19 outbreaks given the difficulty of maintaining social distancing and the fact that hemodialysis patients are at higher risk of being infected with COVID-19. During the COVID-19 pandemic, HCWs have had to face many challenges and stressors. Our study was designed to gain HCWs' perspectives on their experiences of the impacts of the COVID-19 pandemic in hemodialysis units. Methods: Semi-structured interviews were conducted with 22 HCWs (nurses, nephrologists, pharmacists, social workers, patient attendants, security agents) working in five hemodialysis centers in Montreal, between November 2020 and May 2021. The content of the interviews was analyzed using thematic analysis. Results: Four themes were identified during the interviews. The first was the impact of COVID-19 on work organization, regarding which participants reported an increased workload, a need for a consistent information strategy, and positive innovations such as telemedicine. The second theme was challenges associated with communicating and caring for dialysis patients during the pandemic. The third theme was psychological distress experienced by hemodialysis staff and the psychosocial impact of COVID-19 on their personal lives. The fourth theme was recommendations made by participants for future public health emergencies, such as maintaining public health measures, ensuring an adequate supply of protective equipment and developing a consistent communication strategy. Conclusions: During the first and second waves of the COVID-19 pandemic, HCWs working in hemodialysis units faced multiple challenges that impacted their wellbeing and their work. In order to minimize challenges for HCWs in hemodialysis during a future pandemic, the healthcare system should provide an adequate supply of protective equipment, develop effective communication strategies and take into account the psychological distress related to HCWs' professional and personal lives.

A Microsimulation Study Of The Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis Centers

rachel.epstein@bmc.org — Tue, 13 Dec 2022 11:13:31 GMT-08:00

Background National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. Methods We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental costeffectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (RNA versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. Results Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. Conclusions The KDIGO-recommended HCV screening interval (every 6 months) appears not to be a cost-effective use of health care resources, suggesting that reevaluation of less frequent screening strategies should be considered.

Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases

will.herrington@ndph.ox.ac.uk — Tue, 13 Dec 2022 08:16:57 GMT-08:00

Background: Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding. Methods: SCALLOP consortium data on 19,195 participants were used to generate an FGF23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). Results: We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties. Conclusions: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.

A Nationwide Comparative Analysis of Peritoneoscopic and Laparoscopic Techniques for Peritoneal Dialysis Catheter Insertion in Brunei Darussalam

chiaoyuenlim905@gmail.com — Mon, 12 Dec 2022 11:39:33 GMT-08:00

Background: Brunei Darussalam introduced peritoneoscopic insertion of peritoneal dialysis catheter (PDC) as a new method in 2014. The aim of this study was to compare outcomes of PDC insertion technique in the country, using proposed standardized definitions of outcomes. Methods: This study used retrospective analysis of all PDC inserted from 1st January 2015 to 31st December 2020 in the country. Outcomes of both peritoneoscopic and laparoscopic insertion methods were analyzed. Four main categories of outcomes were assessed - 1) operative-related outcomes, 2) infective outcomes, 3) mechanical outcomes and 4) time on PD therapy. Results: During the study period, 145 PDC were inserted. 49 (33.8%) were by peritoneoscopy and 96 (66.2%) laparoscopy. The median time on PD therapy was 54.2 months. Those with a higher BMI and history of previous abdominal or pelvic surgery were more likely to undergo laparoscopic method. There was no significant difference in overall infective and mechanical outcomes between the two methods. There was however significantly more post-operative pain observed in the peritoneoscopic group than in the laparoscopic group (8.2% vs 1.0%, p = 0.045). During the study period, there were 49 dropouts to HD, about half were due to infection. However, there was no statistically significant difference observed in time on PD therapy between the two groups (HR 0.87 in laparoscopic group compared to peritoneoscopic group, 95% CI 0.49 to 1.54; p = 0.636). Conclusions: Peritoneoscopic and laparoscopic PD catheter insertions are both complementary to each other in our local setting. This study has enabled us to scrutinize our PD program, with regards to our PDC insertion experience, with the aim to sustain PD growth in the country.

Onconephrology 2022: An Update

marco.bonilla@icloud.com — Fri, 09 Dec 2022 01:39:13 GMT-08:00

Onconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of onco-therapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney related adverse events from various targeted, immuno and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (Onco-hypertension), and acute kidney injury from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.

Symptom Burden before and after Dialysis Initiation in Older Patients

de Rooij, Esther N.M. — Thu, 10 Nov 2022 06:09:51 GMT-08:00

Correction: Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients

American Society of Nephrology — Tue, 11 Oct 2022 06:28:12 GMT-07:00

Nephrology Program Director Protected Time for Program Administration in the United States

Yuan, Christina M. — Wed, 26 Oct 2022 11:06:56 GMT-07:00

The Immune System and Idiopathic Nephrotic Syndrome

Campbell, Ruth E. — Wed, 05 Oct 2022 09:25:09 GMT-07:00

Idiopathic nephrotic syndrome often responds to immunosuppressive treatment. Nevertheless, this syndrome—and the drugs used to treat it—remain important causes of patient morbidity. Idiopathic nephrotic syndrome is usually caused by minimal change disease or FSGS, diseases that primarily affect the podocytes. In spite of decades of research, the underlying causes of both diseases remain incompletely understood. There is, however, a large body of observational and experimental data linking the immune system with both minimal change disease and FSGS, including associations with systemic infections and hematologic malignancies. Perhaps most compellingly, many different immunomodulatory drugs are effective for treating idiopathic nephrotic syndrome, including biologic agents that have well-defined immune targets. In fact, the unexpected efficacy of targeted therapeutic agents has provided important new insights into the pathogenesis of these diseases. Given the large number of drugs that are available to deplete or block specific cells and molecules within the immune system, a better understanding of the immunologic causes of idiopathic nephrotic syndrome may lead to better diagnostic and therapeutic approaches.

Overview of the Medical Management of the Critically Ill Patient

Martinez, Rebecca H. — Fri, 18 Nov 2022 05:09:20 GMT-08:00

The medical management of the critically ill patient focuses predominantly on treatment of the underlying condition (e.g., sepsis or respiratory failure). However, in the past decade, the importance of initiating early prophylactic treatment for complications arising from care in the intensive care unit setting has become increasingly apparent. As survival from critical illness has improved, there is an increased prevalence of postintensive care syndrome—defined as a decline in physical, cognitive, or psychologic function among survivors of critical illness. The Intensive Care Unit Liberation Bundle, a major initiative of the Society of Critical Care Medicine, is centered on facilitating the return to normal function as early as possible, with the intent of minimizing iatrogenic harm during necessary critical care. These concepts are universally applicable to patients seen by nephrologists in the intensive care unit and may have particular relevance for patients with kidney failure either on dialysis or after kidney transplant. In this article, we will briefly summarize some known organ-based consequences associated with critical illness, review the components of the ABCDEF bundle (the conceptual framework for Intensive Care Unit Liberation), highlight the role nephrologists can play in implementing and complying with the ABCDEF bundle, and briefly discuss areas for additional research.

How I Treat Focal Segmental Glomerulosclerosis

Liew, Adrian — Tue, 23 Aug 2022 07:06:41 GMT-07:00

A Blueprint for Assessing Affordability of SGLT2 Inhibitors in the United States

Khine, Annika — Wed, 02 Nov 2022 07:07:07 GMT-07:00

Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes

Vart, Priya — Tue, 22 Nov 2022 05:49:08 GMT-08:00

Toward Guideline-Directed Medical Therapy in Nephrology

Zeitler, Evan M. — Tue, 22 Nov 2022 07:10:33 GMT-08:00

Community Houses to Increase Access to Home Dialysis

Walker, Rachael — Fri, 14 Oct 2022 08:50:05 GMT-07:00

Effect of Furosemide on Proximal Tubular Secretion of Organic Solutes in Patients Receiving Hemodialysis

Sirich, Tammy L. — Tue, 04 Oct 2022 10:46:23 GMT-07:00

Cost-Effectiveness of Dapagliflozin as a Treatment for Chronic Kidney Disease

McEwan, Phil — Wed, 02 Nov 2022 06:03:30 GMT-07:00

Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes

Østergaard, Helena Bleken — Fri, 04 Nov 2022 07:10:25 GMT-07:00

Menstrual Abnormalities and Reproductive Lifespan in Females with CKD

Rytz, Chantal L. — Wed, 23 Nov 2022 05:36:35 GMT-08:00

A Survey of Environmental Sustainability Practices in Dialysis Facilities in Australia and New Zealand

Talbot, Benjamin — Fri, 11 Nov 2022 07:12:04 GMT-08:00

Bardoxolone Methyl for Alport Syndrome: Opportunities and Challenges

Quinlan, Catherine — Mon, 21 Nov 2022 11:30:28 GMT-08:00

Obesity in CKD

Friedman, Allon N. — Tue, 20 Sep 2022 06:25:15 GMT-07:00

Reproductive Health in Women with Kidney Disease

Gumber, Ramnika — Wed, 23 Nov 2022 05:36:35 GMT-08:00

Effects of Bardoxolone Methyl in Alport Syndrome

Warady, Bradley A. — Mon, 21 Nov 2022 11:30:28 GMT-08:00

Gout Among Dialysis Patients: Prevalence, Associated Factors, Treatment Patterns, and Outcomes; Population-Based Retrospective Cohort Study

bmarder@horizontherapeutics.com — Tue, 06 Dec 2022 01:28:30 GMT-08:00

Background: An association between gout and non-dialysis chronic kidney disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in end-stage renal disease (ESRD) patients undergoing dialysis. Methods: Using data from US Renal Data System (USRDS), we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Anti-gout medications and impact on anemia management were assessed and compared between gout and non-gout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1-year of study follow-up were compared between gout and non-gout patients using multivariate Cox regression models. Results: Of 231,841 ESRD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had 1 or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male gender, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating-agent (ESA) requirements (OR=1.18 for high vs. low ESA dose, 95% 1.14 to 1.22) and likelihood of blood transfusions (OR=1.34, 95% CI 1.30 to 1.38). During the 1-year study follow-up, mortality among gout vs non-gout patients was higher by 3% (95% CI: 0-6%), and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI: 3-9%) after adjusting for comorbid conditions. Conclusions: A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.

Dynein-mediated trafficking, a new mechanism of diabetic podocytopathy

hua-sun@uiowa.edu — Tue, 06 Dec 2022 01:28:30 GMT-08:00

Background: Diabetic nephropathy (DN) is characterized by increased endocytosis and degradation of nephrin, a protein that comprises the molecular sieve of the glomerular filtration barrier. While nephrin internalization has been found activated in diabetes-stressed podocytes, the post-internalization trafficking steps that lead to the eventual depletion of nephrin and the development of DN are unclear. Our work on an inherited podocytopathy uncovered that dysregulated dynein could compromise nephrin trafficking, leading us to test whether and how dynein mediates the pathogenesis of DN. Methods: We analyzed the transcription of dynein components in public DN databases, using the Nephroseq platform. We verified altered dynein transcription in diabetic podocytopathy by quantitative PCR. Dynein-mediated trafficking and degradation of nephrin was investigated using an in vitro nephrin trafficking model and was demonstrated in a mouse model with streptozotocin (STZ)-induced DN, as well as in human kidney biopsy sections. Results: Our transcription analysis revealed increased expression of dynein in human DN and diabetic mouse kidney, correlated significantly with the severity of hyperglycemia and DN. In diabetic podocytopathy, we observed that dynein-mediated post-endocytic sorting of nephrin was upregulated, resulting in accelerated nephrin degradation and disrupted nephrin recycling. In hyperglycemia-stressed podocytes, Dynll1, one of the most upregulated dynein components, is required for the recruitment of dynein complex that mediates the post-endocytic sorting of nephrin. This was corroborated by observing enhanced Dynll1-nephrin colocalization in podocytes of diabetic patients, as well as dynein-mediated trafficking and degradation of nephrin in STZ-induced diabetic mice with hyperglycemia. Knockdown of Dynll1 attenuated lysosomal degradation of nephrin and promoted its recycling, suggesting the essential role of Dynll1 in dynein-mediated mistrafficking. Conclusion: Our studies show that hyperglycemia stimulates dynein-mediated trafficking of nephrin to lysosomes by inducing its expression. The decoding of dynein-driven pathogenesis of diabetic podocytopathy offers a spectrum of new dynein-related therapeutic targets for DN.

Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney Failure

rappold.ana@epa.gov — Tue, 06 Dec 2022 10:17:15 GMT-08:00

Background: Ambient PM2.5 is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. Methods: We conducted a retrospective open cohort study from 1-1-2008 to 12-31-2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1 km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. Results: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10 µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (RR: 1.01, 95% CI: 1.01, 1.02) and lower hemoglobin (RR: 1.02, 95%CI: 1.01, 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. Conclusions: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.

Incisional hernia development after live donor nephrectomy: Impact of surgical technique

bernard.j.dubray@vumc.org — Tue, 06 Dec 2022 10:17:15 GMT-08:00

Background: Characteristics of incisional hernia (IH) formation following live donor nephrectomy (LDN) are not well defined. The goal of this study was to describe the incidence of IH within 3 years following LDN and identify risk factors contributing to their formation. Materials and methods: We performed a single center, retrospective review of all LDN between February 2013 to October 2018. Patients with and without IH were compared based on donor and operative variables. Data were analyzed using chi square tests with column proportions. Multivariable logistic regression with backwards elimination was used to evaluate the likelihood of IH based on potential risk factors. Results: Three hundred and one individuals underwent live donor nephrectomy. Twenty-eight patients (9.3%) developed an incisional hernia with median time to development of 7 months (range: 2-24 months). Obesity [Body Mass Index (BMI) ≥30], periumbilical hand port, and vertical infraumbilical hand port were associated with increased risk of IH development on univariate analysis. On multivariate analysis, obesity and periumbilical hand port location were persistent risk factors for IH. Conclusions: The incidence of IH following LDN is prevalent and associated with obesity and operative technique. Placing the hand port infraumbilical with a transverse fascial incision may reduce the risk of IH following LDN.

Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis Patients

angelo.karaboyas@arborresearch.org — Mon, 05 Dec 2022 11:21:39 GMT-08:00

Background: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. Methods: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5,117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol, or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with vs. without gout. Outcomes included erythropoietin resistance index (ERI = ESA dose/(hemoglobin*weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). Results: Gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9-12%). Both HD and PD patients with gout (vs. no gout) were older, more likely male, with higher BMI, and higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate lowering therapy. After propensity score matching, mean ERI was 3-6% higher for gout vs. non-gout patients, while there was minimal evidence of association with clinical outcomes or PROs. Conclusion: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely underreported. Gout was not associated with adverse clinical or patient-reported outcomes.

Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

Kjell.Tullus@gosh.nhs.uk — Thu, 01 Dec 2022 12:41:52 GMT-08:00

Rituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short to medium term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multi-drug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen and the concomitant use of maintenance immunosuppression. Following repeated treatments, patients are found to have an improving response overall with longer relapse-free period. The drug effect, however, is not permanent and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance to understand the long-term safety profile upon repeated treatments. Although rituximab appears to be generally safe, there are concerns of long-term hypogammaglobulinaemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side-effects, persistent hypogammaglobulinaemia and to guide on re-dosing strategy. In this review, we highlight recent advances on the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.

Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?

Ayorinde, John O.O. — Wed, 09 Nov 2022 06:42:55 GMT-08:00

Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system. In the extreme, deployment of highly performant but “black box” AI is fraught with risk, and high-profile errors could damage future trust in the technology. Furthermore, a major factor determining whether new systems are adopted in clinical settings is whether they are “trusted” by clinicians. Key to unlocking trust will be designing platforms optimized for intuitive human-AI interactions and ensuring that, where judgment is required to resolve ambiguous areas of assessment, the workings of the AI image classifier are understandable to the human observer. Therefore, determining the optimal design for AI systems depends on factors beyond performance, with considerations of goals, interpretability, and safety constraining many design and engineering choices. In this article, we explore challenges that arise in the application of AI to renal histopathology, and consider areas where choices around model architecture, training strategy, and workflow design may be influenced by factors beyond the final performance metrics of the system.

Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

Doan Ngoc, Tra-My — Mon, 24 Oct 2022 08:45:27 GMT-07:00

Targeting the Right Metrics for Kidney Transplantation Success

Sharif, Adnan — Wed, 12 Oct 2022 11:47:37 GMT-07:00

A Step toward Understanding the Story Behind the Pictures: Molecular Diagnostics and the Banff Classification of Renal Allograft Pathology

Bissonnette, Mei Lin Z. — Wed, 28 Sep 2022 09:06:46 GMT-07:00

Authors’ Reply: In Silico–Based Approach to the Discovery of New Antigens in Membranous Nephropathy

Sealfon, Rachel — Thu, 29 Sep 2022 10:43:10 GMT-07:00

Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy

Zhao, Jin — Tue, 30 Aug 2022 07:22:47 GMT-07:00

Nephrotic Syndrome Gene TBC1D8B Is Required for Endosomal Maturation and Nephrin Endocytosis in Drosophila

Milosavljevic, Julian — Thu, 22 Sep 2022 11:18:08 GMT-07:00

Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance

Holle, Johannes — Fri, 19 Aug 2022 10:51:51 GMT-07:00

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination

Canney, Mark — Fri, 04 Nov 2022 01:16:32 GMT-07:00

mRNA COVID-19 Vaccines and Their Risk to Induce a Relapse of Glomerular Diseases

Kronbichler, Andreas — Fri, 04 Nov 2022 01:16:32 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Wed, 30 Nov 2022 10:00:30 GMT-08:00

Skeletal Outcomes in Children and Young Adults with Glomerular Disease

Goodwin Davies, Amy J. — Wed, 28 Sep 2022 07:50:27 GMT-07:00

Slit Diaphragms: Junctions That Never Sleep

Drummond, Iain A. — Fri, 04 Nov 2022 07:11:15 GMT-07:00

Banff Human Organ Transplant Transcripts Correlate with Renal Allograft Pathology and Outcome: Importance of Capillaritis and Subpathologic Rejection

Rosales, Ivy A. — Wed, 31 Aug 2022 11:57:52 GMT-07:00

Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases

Mitrofanova, Alla — Wed, 05 Oct 2022 09:45:00 GMT-07:00

In Silico–Based Approach to the Discovery of New Antigens in Membranous Nephropathy

Takahashi-Kobayashi, Mayumi — Thu, 29 Sep 2022 10:43:09 GMT-07:00

Designing Interventions Addressing Structural Racism to Reduce Kidney Health Disparities: A Report from a National Institute of Diabetes and Digestive and Kidney Diseases Workshop

Crews, Deidra C. — Wed, 19 Oct 2022 12:40:55 GMT-07:00

Structural racism embodies the many ways in which society fosters racial discrimination through “mutually reinforcing inequitable systems” that limit access to resources and opportunities that can promote health and well being among marginalized communities. To achieve health equity, and kidney health equity more specifically, structural racism must be eliminated. In February 2022, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “Designing Interventions that Address Structural Racism to Reduce Kidney Health Disparities” workshop, which was aimed at describing the mechanisms through which structural racism contributes to health and health care disparities for people along the continuum of kidney disease and identifying actionable opportunities for interventional research focused on dismantling or addressing the effects of structural racism. Participants identified six domains as key targets for interventions and future research: (1) apply an antiracism lens, (2) promote structural interventions, (3) target multiple levels, (4) promote effective community and stakeholder engagement, (5) improve data collection, and (6) advance health equity through new health care models. There is an urgent need for research to develop, implement, and evaluate interventions that address the unjust systems, policies, and laws that generate and perpetuate inequities in kidney health.

HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant Candidates

Isaacson, Dylan — Wed, 31 Aug 2022 11:57:52 GMT-07:00

Anatomical Evidence for Parasympathetic Innervation of the Renal Vasculature and Pelvis

Cheng, Xiaofeng — Mon, 17 Oct 2022 07:25:15 GMT-07:00

Prediagnostic Appearance of THSD7A Autoantibodies in Membranous Nephropathy

burbelop@nidcr.nih.gov — Tue, 29 Nov 2022 01:46:51 GMT-08:00

Background: Pathogenic autoantibodies against thrombospondin type-1 domain 7A (THSD7A) are present in approximately 3% of patients with membranous nephropathy (MN). Compared to PLA2R antibodies, less is known about THSD7A autoantibodies (AB) due to the relative rarity and lack of a commercially, available quantitative immunoassay. Methods: Here we describe the development and validation of a highly quantitative, luciferase immunoprecipitation systems (LIPS) assay for detecting THSD7A AB and used it to study dominant THSD7A epitopes, disease associations and monitoring disease activity. The Department of Defense Serum Repository (DODSR) was then used to analyze THSD7A AB in 371 longitudinal serum samples collected before clinical diagnosis of MN from 110 PLA2R-negative MN subjects. Results: LIPS analysis demonstrated that a near full-length THSD7A (amino acids 1-1656) detected robust autoantibody levels in all known seropositive MN patients with 100% sensitivity and specificity compared to ELISA and/or Western blotting. The majority of THSD7A seropositive subjects in our pilot cohort had evidence of coexisting autoimmunity or cancer. Moreover, three THSD7A seropositive cases undergoing immunosuppressive therapy showed longitudinal autoantibody levels that tracked clinical status. Additional epitope analysis of two smaller protein THSD7A fragments spanning amino acids 1-416 and 1-671 demonstrated lower sensitivity of 32% and 44%, respectively. In the DODSR cohort, THSD7A seropositivity was detected in 4.5% of PLA2R negative MN cases. In one "primary" and in one secondary MN-associated with cancer, THSD7A AB were detectable less than one month prior to biopsy-proven diagnosis. In addition, 3 cases of lupus membranous nephropathy had detectable THSD7A AB years before hypoalbuminemia and biopsy-proven diagnosis. Conclusions: While further studies are needed to explore the significance of THSD7A AB in lupus membranous nephropathy, this study describes a novel, highly sensitive LIPS immunoassay for detecting THSD7A AB and adds to the existing literature on THSD7A-associated MN.

Fetal Nephrology: A Quaternary Care Center Experience

mcbraun@texaschildrens.org — Tue, 29 Nov 2022 01:46:51 GMT-08:00

Background: Congenital anomalies of kidney and urinary tract (CAKUT) represent 15-20% of prenatally diagnosed abnormalities. Maternal characteristics, the frequency of various forms of renal disease including CAKUT referred for prenatal nephrology consultation and their perinatal outcomes are less well defined. Methods: Performed a retrospective chart review of fetal CAKUT and other forms of renal disease referred for prenatal nephrology consults at Texas Children's Hospital Fetal Center from January 1st 2012 to December 31st 2018. Results: 217 prenatal nephrology consultations were performed during the study period, representing 4.7% of total Fetal Center referrals at a mean estimated gestational age of 25.2 ±5.7 weeks. Maternal characteristics: Mean age 29.3±5.6 years; 14% had advanced maternal age; 10% had a family history of CAKUT or ESKD, 5% had diabetes mellitus, and 5% of pregnancies were in vitro fertilization assisted. Fetal characteristics: 62.7% of fetuses were male, and 16% had CAKUT associated with multiple congenital anomalies. The most common prenatal diagnoses were Lower Urinary Tract Obstruction in 71 (32.7%), unilateral renal agenesis or multicystic dysplastic kidney (MCDK) in 52 (24.9%), bilateral agenesis or MCDK in 22 (10.1%), and bilateral cystic renal disease in 19 (8.8%). 76% of patients received genetic counseling. 141 (64.9%) patients had some form of prenatal genetic testing with a positivity rate of 5.7% Post-natal characteristics: 61 (28.1%) of patients were seen in prenatal consultation only, and no follow up was available. Of the remaining 156 pregnancies, 136 (86.3%) were viable and delivered at mean gestational age of 35.2± 3.8 weeks. Of these, 100 (64%) survived to discharge. Additional post-natal genetic testing was obtained on 27 infants with a positivity rate of 59%. Conclusions: Overall perinatal mortality for this cohort as a whole was high (35.8%). While prenatal genetic testing had a limited diagnostic utility, targeted post-natal genetic testing had a much higher diagnostic yield.

Digital spatial profiling of glomerular gene expression in pauci-immune focal necrotizing glomerulonephritis

andre.oszwald@meduniwien.ac.at — Tue, 29 Nov 2022 01:46:51 GMT-08:00

Introduction: Pauci-immune focal necrotizing glomerulonephritis (piFNGN) involves asynchronous onset and progression of injurious lesions in biopsies. Pathologists describe this heterogeneity within a biopsy, but translating the information into prognostic or expression analyses is challenging. Understanding the underlying molecular processes could improve treatment; however, bulk or single cell transcriptomic analyses of dissociated tissue disregard the heterogeneity of glomerular injury. Methods: We characterize protein and mRNA expression of individual glomeruli in 20 biopsies from 18 patients with anti-neutrophil cytoplasmic antibody-associated piFNGN using the Nanostring digital spatial profiling (DSP) platform. For this purpose, circular annotations of glomeruli were analyzed using protein, immuno-oncology RNA, and cancer transcriptome atlas panels (n=120, 72, and 48 glomeruli, respectively). Histological evaluation of glomerular patterns of injury was performed in adjacent serial sections. Expression data was processed by log2 transformation, quantile normalization and batch adjustment. Results: DSP revealed distinct but overlapping gene expression profiles relating to the morphological evolution of injurious lesions, including dynamic expression of various immune checkpoint regulators. Enrichment analysis indicated deregulated pathways that underline known and highlight novel potential mechanisms of disease. Moreover, by capturing individual glomeruli, DSP describes heterogeneity between and within biopsies. Conclusions: We demonstrate the benefit of spatial profiling for characterization of heterogeneous glomerular injury, indicating novel molecular correlates of glomerular injury in piFNGN.

PPARδ agonism ameliorates renal fibrosis in an Alport syndrome mouse model

jeffminer@wustl.edu — Tue, 29 Nov 2022 01:46:51 GMT-08:00

Background: Alport syndrome is a genetic kidney disease caused by mutation in any of the COL4A3, COL4A4 or COL4A5 genes encoding the type IV collagen α3, α4, and α5 chains. Defects of type IV collagen α3α4α5 cause glomerular basement membrane abnormalities and lead to defects in glomerular filtration and end stage kidney disease. Treatment with angiotensin converting enzyme inhibitors (ACEi) dramatically slows disease progression but does not stop progression to renal failure. Therefore, novel therapeutic options with different modes of action from ACEi are needed. Peroxisome proliferator-activated receptor (PPAR) δ agonists have shown renoprotective effects in several acute kidney injury mouse models. In the present study, we investigated the effects of a potent and selective PPARδ agonist, REN001 (formerly HPP593), in a mouse model of Alport syndrome. Methods: We administered REN001 from the early stages to the late stages of disease via once daily intraperitoneal injections. Results: REN001 treatment halved proteinuria at the late stages of disease in Col4a3-/- mice. Blood urea nitrogen levels were also decreased, and histological and molecular analyses showed that REN001 ameliorated renal inflammation and fibrosis. Conclusions: These results indicate that REN001 slows kidney disease progression in Alport mice. REN001 has a different mechanism of action from ACEi, so we therefore hypothesize that combining the two treatments may show additive effects to attenuate renal injury and slow progression to renal failure.

Safety and Adequacy of Kidney Biopsy Procedure in Patients with Obesity

dennis.moledina@yale.edu — Tue, 29 Nov 2022 01:46:51 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Global Dialysis Perspective: Nicaragua

cacarjimenna@gmail.com — Tue, 29 Nov 2022 01:46:51 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Negative modulation of B cell activation by MC1R signaling protects against membranous nephropathy

rujun.gong@utoledo.edu — Tue, 29 Nov 2022 12:51:00 GMT-08:00

Background: The pituitary neuropeptide melanocortins, and specifically ACTH, have recently emerged as a novel therapeutic modality for membranous nephropathy (MN). However, the mechanism(s) of action remains elusive. Methods: Passive Heymann nephritis (PHN), a model of MN, was induced in wild-type (WT) rats and melanocortin 1 receptor (MC1R) knockout (KO) rats generated by the CRISPR/Cas9 technology, followed by treatment with various melanocortin agents, including Repository Corticotropin Injection, the non-steroidogenic pan-MCR agonist NDP-MSH, and the selective MC1R agonist MS05. Additional rats received adoptive transfer of syngeneic bone marrow-derived cells (BMDC) beforehand. Kidney function, histology and molecular changes were evaluated. Results: MC1R KO worsened PHN, associated with increased deposition of autologous IgG and complement C5b-9 in glomeruli and higher circulating levels of autologous IgG, as evidence of a sensitized humoral immune response. Melanocortin therapy ameliorated PHN in WT rats, coinciding with reduced glomerular deposition of autologous IgG and C5b-9. The beneficial efficacy of melanocortins was blunted in KO rats but was restored by adoptive transfer of syngeneic BMDC derived from WT rats. Mechanistically, MC1R was expressed in B lymphocytes, and negatively associated with B cell activation as revealed by gene set enrichment analysis. MC1R agonism triggered MITF induction in activated B cells in a cAMP-dependent mode, and repressed the expression of IRF4, a lymphoid transcription factor essential for B cell development and maturation, resulting in suppressed plasmacytic differentiation and IgG production. Conclusion: MC1R signaling negatively modulates B cell activation and suppresses humoral immune responses in PHN, representing a novel therapeutic target for MN.

Risk Stratification to Predict Renal Survival in Anti-GBM Disease

Silke.Brix@mft.nhs.uk — Tue, 29 Nov 2022 12:51:00 GMT-08:00

Anti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P<0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P<0.001, P<0.001). Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P<0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P<0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N<10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N<10%), respectively. In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.

Association of Shear Stress with Subsequent Lumen Remodeling in Hemodialysis Arteriovenous Fistulas

Yong.He@surgery.ufl.edu — Tue, 29 Nov 2022 11:05:50 GMT-08:00

Background Blood flow-induced wall shear stress (WSS) is a strong local regulator of vascular remodeling, but its effects on arteriovenous fistula (AVF) remodeling are unclear. Methods In this prospective cohort study, we used statistical mixed-effects modeling to investigate the associations between WSS and AVF remodeling in 120 participants undergoing AVF creation surgery. Postoperative magnetic resonance imaging data at 1 day, 6 weeks, and 6 months were used to derive current WSS by computational fluid dynamic simulations and to quantify subsequent changes in AVF lumen cross-sectional area at 1-mm intervals along the proximal artery and AVF vein. Results Combining artery and vein data, prior mean WSS was significantly associated with lumen area expansion. Mean WSS at day 1 was significantly associated with lumen area change from day 1 to week 6 (11% larger week-6 area per IQR increase in day-1 mean WSS, 95% CI 5%-18%; n=101), and mean WSS at 6 weeks was significantly associated with lumen area change from week 6 to month 6 (14% larger area per IQR increase, 95% CI 3%-28%; n=52). The association of mean WSS at day 1 with lumen area expansion from day 1 to week 6 differed significantly by diabetes (p=0.009): 27% (95% CI 17%-37%) larger area per IQR increase in mean WSS without diabetes, and 9% (95% CI -1-19%) with diabetes. Day-1 oscillatory shear index (OSI) was significantly associated with lumen area change from day 1 to week 6 (5% smaller area per IQR increase in OSI, 95% CI 3%-7%), and OSI at week 6 was significantly associated with lumen change from week 6 to month 6 (7% smaller area per IQR increase in OSI, 95% CI 2%-11%). WSS spatial gradient was not significantly associated with subsequent remodeling. In a joint model, WSS and OSI statistically significantly interacted in their associations with lumen area expansion in a complex nonlinear fashion. Conclusion Higher WSS and lower OSI were associated with greater lumen expansion after AVF creation surgery.

Pathophysiology of AV Fistula Maturation and Non-Maturation

maurizio.gallieni@unimi.it — Tue, 29 Nov 2022 11:05:50 GMT-08:00

Genomic Disorders in CKD across the Lifespan

Verbitsky, Miguel — Thu, 27 Oct 2022 11:46:36 GMT-07:00

Reproductive Healthcare is a Key Component of Comprehensive Care for Adolescents with CKD

mmoxeymims@childrensnational.org — Wed, 23 Nov 2022 10:51:15 GMT-08:00

Association of Bradycardia and Asystole Episodes with Dialytic Parameters: An Analysis of the Monitoring in Dialysis (MiD) Study

Soomro, Qandeel H. — Tue, 11 Oct 2022 12:10:49 GMT-07:00

Associations of Metabolic Syndrome and Abdominal Obesity with Anion Gap Metabolic Acidosis among US Adults

Lambert, Douglas C. — Wed, 13 Jul 2022 02:01:21 GMT-07:00

Telemonitoring for Hypertension Management: The Time Is Now

Karam, Sabine — Wed, 05 Oct 2022 05:56:19 GMT-07:00

In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride Cotransporter

Wu, Aihua — Fri, 26 Aug 2022 11:27:03 GMT-07:00

Patient Perspective on Xenotransplantation

Baliker, Mary — Wed, 12 Oct 2022 05:55:27 GMT-07:00

An Unsuspected Histological Finding in a Patient with Cancer and AKI

Hengel, Felicitas E. — Wed, 23 Nov 2022 07:45:30 GMT-08:00

Delivery of Active Medical Management without Dialysis through an Embedded Kidney Palliative Care Model

Bursic, Alexandra E. — Tue, 19 Jul 2022 01:29:42 GMT-07:00

In Memoriam: Jerry Yee, MD

Choi, Michael J. — Wed, 05 Oct 2022 07:21:44 GMT-07:00

Point of Care Ultrasound in Cirrhosis-Associated Acute Kidney Injury: Beyond Inferior Vena Cava

Koratala, Abhilash — Wed, 05 Oct 2022 05:56:19 GMT-07:00

Proinflammatory Diets and Risk of ESKD in US Adults with CKD

Banerjee, Tanushree — Wed, 07 Sep 2022 01:31:55 GMT-07:00

Minding the Gap Beyond Kidney Disease: Utility of the Anion Gap in Metabolic Syndrome

Tamargo, Christina — Wed, 23 Nov 2022 07:45:30 GMT-08:00

Short-Term Mortality Associated with Outpatient Vascular Access Restoration Procedures

Paratane, Deepika — Wed, 12 Oct 2022 05:55:27 GMT-07:00

Magnetic Resonance Elastography as Surrogate Marker of Interstitial Fibrosis in Kidney Transplantation: A Prospective Study

Chauveau, Bertrand — Wed, 07 Sep 2022 01:31:55 GMT-07:00

Complications Associated with Continuous RRT

Gautam, Samir C. — Mon, 12 Sep 2022 09:23:15 GMT-07:00

Continuous renal replacement therapy (CRRT) is a form of renal replacement therapy that is used in modern intensive care units (ICUs) to help manage acute kidney injury (AKI), end stage kidney disease (ESKD), poisonings, and some electrolyte disorders. CRRT has transformed the care of patients in the ICU over the past several decades. In this setting, it is important to recognize CRRT-associated complications but also up-to-date management of these complications. Some of these complications are minor, but others may be more significant and even life-threatening. Some CRRT complications may be related to dialysis factors and others to specific patient factors. Our overarching goal in this article is to review and discuss the most significant CRRT-related complications at the different stage of management of CRRT. With the advent of newer solutions, there have been newer complications as well.

Quality of Life in Patients with Chronic Kidney Disease Managed with or without Dialysis: An Observational Study

So, Sarah — Wed, 13 Jul 2022 10:48:31 GMT-07:00

A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome

Kohler, Jennefer — Wed, 26 Oct 2022 02:03:07 GMT-07:00

Importance of Confounding Factors in the Evaluation of Surrogate Measures for Kidney Transplant Fibrosis

Adam, Benjamin A. — Wed, 23 Nov 2022 07:45:30 GMT-08:00

Genital Edema in a Patient on Continuous Ambulatory Peritoneal Dialysis

Thammathiwat, Theerachai — Wed, 23 Nov 2022 07:45:30 GMT-08:00

Heme Proteins and Kidney Injury: Beyond Rhabdomyolysis

Nath, Karl A. — Wed, 05 Oct 2022 09:24:11 GMT-07:00

Heme proteins, the stuff of life, represent an ingenious biologic strategy that capitalizes on the biochemical versatility of heme, and yet is one that avoids the inherent risks to cellular vitality posed by unfettered and promiscuously reactive heme. Heme proteins, however, may be a double-edged sword because they can damage the kidney in certain settings. Although such injury is often viewed mainly within the context of rhabdomyolysis and the nephrotoxicity of myoglobin, an increasing literature now attests to the fact that involvement of heme proteins in renal injury ranges well beyond the confines of this single disease (and its analog, hemolysis); indeed, through the release of the defining heme motif, destabilization of intracellular heme proteins may be a common pathway for acute kidney injury, in general, and irrespective of the underlying insult. This brief review outlines current understanding regarding processes underlying such heme protein-induced acute kidney injury (AKI) and chronic kidney disease (CKD). Topics covered include, among others, the basis for renal injury after the exposure of the kidney to and its incorporation of myoglobin and hemoglobin; auto-oxidation of myoglobin and hemoglobin; destabilization of heme proteins and the release of heme; heme/iron/oxidant pathways of renal injury; generation of reactive oxygen species and reactive nitrogen species by NOX, iNOS, and myeloperoxidase; and the role of circulating cell-free hemoglobin in AKI and CKD. Also covered are the characteristics of the kidney that render this organ uniquely vulnerable to injury after myolysis and hemolysis, and pathobiologic effects emanating from free, labile heme. Mechanisms that defend against the toxicity of heme proteins are discussed, and the review concludes by outlining the therapeutic strategies that have arisen from current understanding of mechanisms of renal injury caused by heme proteins and how such mechanisms may be interrupted.

Bardoxolone for CKD: The Paradox of Confusion and Dogma

Avula, Uma Mahesh R. — Wed, 07 Sep 2022 01:31:55 GMT-07:00

Potassium Homeostasis and WNK Kinases in the Regulation of the Sodium-Chloride Cotransporter: Hyperaldosteronism and Its Metabolic Consequences

Johnston, Jermaine G. — Wed, 23 Nov 2022 07:45:30 GMT-08:00

Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled Study

Hosojima, Michihiro — Mon, 17 Oct 2022 01:50:35 GMT-07:00

SARS-CoV-2 Infections among Vaccinated Patients on Maintenance Dialysis, January 1–August 31, 2021, United States

Bardossy, Ana Cecilia — Tue, 20 Sep 2022 07:33:25 GMT-07:00

Global Dialysis Perspective: Italy

Pani, Antonello — Wed, 31 Aug 2022 12:01:56 GMT-07:00

Global Dialysis Perspective: Kenya

Maritim, Peter K.K. — Mon, 05 Sep 2022 07:01:22 GMT-07:00

Screening for Cardiovascular Disease in CKD: COMMENTARY

McCallum, Wendy — Mon, 28 Feb 2022 06:11:13 GMT-08:00

Screening for Cardiovascular Disease in CKD: PRO

Jain, Nishank — Mon, 28 Feb 2022 06:11:13 GMT-08:00

Screening for Cardiovascular Disease in CKD: CON

Ramos, Giana K. — Mon, 28 Feb 2022 06:11:13 GMT-08:00

Sodium-Glucose Cotransporter 2 Inhibitors and Urinary Tract Infection: Is There Room for Real Concern?

Wiegley, Nasim — Mon, 12 Sep 2022 11:24:13 GMT-07:00

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized our armamentarium for kidney and heart protection in patients with or without diabetes. Based on early reports of a limited number of cases, a concern for increased risk of urinary tract infections arose, which has become one of the main areas of concern for some clinicians. However, data from large randomized clinical trials and real-world population-based studies have not shown a significantly increased risk of UTI in patients on SGLT2 inhibitors. The goal of this brief review article is to review the literature and provide reassurance to patients and prescribers for the broader use of these agents.

Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2

shuta.ishibe@yale.edu — Tue, 22 Nov 2022 11:54:51 GMT-08:00

Background: Intact expression of podocyte histone deacetylases (HDAC) during development is essential for maintaining a normal glomerular filtration barrier due to its role in modulating DNA damage and preventing premature senescence. Methods: Germline podocyte-specific Hdac1 and 2 (Hdac1/2) double knockout mice were generated to examine the importance of these enzymes during development. Results: Podocyte-specific loss of Hdac1/2 in mice resulted in severe proteinuria, kidney failure, and collapsing glomerulopathy. Hdac1/2-deprived podocytes exhibited classic characteristics of senescence, such as senescence-associated β-galactosidase activity and lipofuscin aggregates. In addition, DNA damage, likely caused by epigenetic alterations such as open chromatin conformation, not only resulted in podocyte cell-cycle entry as shown in vivo by Ki67 expression and by FUCCI-2aR mice, but also in p21-mediated cell-cycle arrest. Through the senescence secretory associated phenotype, the damaged podocytes secreted proinflammatory cytokines, growth factors, and matrix metalloproteinases, resulting in subsequent podocyte detachment and loss, evidenced by senescent podocytes in urine. Conclusions: Hdac1/2 play an essential role during development. Loss of these genes in double knockout mice leads to sustained DNA damage and podocyte senescence and loss.

Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs

Friedhelm.Hildebrandt@childrens.harvard.edu — Tue, 22 Nov 2022 11:54:51 GMT-08:00

Background About 40 disease genes have been described to date for isolated congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of childhood chronic kidney disease. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in such biologic processes as cell migration and focal adhesion, acts downstream of integrin linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva, leading to CAKUT in mice with this variant. Methods To identify novel genes that, when mutated, result in CAKUT, we performed exome sequencing in an international cohort of 1265 families with CAKUT. We also assessed the effects in vitro of wild-type and mutant ARHGEF6 proteins, as well as the effects of Arhgef6 deficiency in mouse and frog models. Results We detected six different hemizygous variants in the gene ARHGEF6 (which is located on the X chromosome in humans) in eight individuals from six families with CAKUT. In kidney cells, overexpression of wild-type ARHGEF6—but not proband-derived mutant ARHGEF6— increased active levels of CDC42/RAC1, induced lamellipodia formation, and stimulated PARVAdependent cell spreading. ARHGEF6 mutant proteins showed loss of interaction with PARVA. Three-dimensional MDCK cell cultures expressing ARHGEF6 mutant proteins exhibited reduced lumen formation and polarity defects. Arhgef6 deficiency in mouse and frog models recapitulated features of human CAKUT. Conclusions Deleterious variants in ARHGEF6 may cause dysregulation of integrin-parvinRAC1/CDC42 signaling, thereby leading to X-linked CAKUT.

Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft Failure

Denic, Aleksandar — Thu, 17 Nov 2022 05:41:00 GMT-08:00

Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Refardt, Julie — Thu, 17 Nov 2022 05:40:59 GMT-08:00

National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations

Diao, James A. — Fri, 11 Nov 2022 07:11:15 GMT-08:00

Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation

Peng, Jiahui — Wed, 19 Oct 2022 10:34:21 GMT-07:00

Short-Term Effects of Potassium Chloride Supplementation on Fibroblast Growth Factor 23 and Phosphate in Chronic Kidney Disease

m.h.yeung@umcg.nl — Thu, 10 Nov 2022 10:51:25 GMT-08:00

Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome

Viering, Daan H.H.M. — Thu, 27 Oct 2022 11:46:36 GMT-07:00

The Role of Platelet-Derived Growth Factor in Focal Segmental Glomerulosclerosis

Jia, Ting — Wed, 09 Nov 2022 06:42:55 GMT-08:00

Context Matters: A Qualitative Synthesis of Adherence Literature for People on Hemodialysis

ktaylo45@jhmi.edu — Tue, 08 Nov 2022 01:37:17 GMT-08:00

Background: Patients with end-stage kidney disease treated with hemodialysis in the U.S. have persistently higher rates of nonadherence compared to patients in other developed countries. Nonadherence is associated with increased risk of death and higher medical expenditure. There is an urgent need to address it with feasible, effective interventions as the prevalence of patients on hemodialysis in the U.S. continues to grow. However, published adherence interventions demonstrate limited long-term efficacy. Methods: We conducted a synthesis of qualitative studies on adherence to hemodialysis treatment, medications, and fluid and dietary restrictions to identify gaps in published adherence interventions, searching PubMed, CINAHL, PsychInfo, Embase, and Web of Science databases. We analyzed qualitative data with a priori codes derived from the World Health Organization's adherence framework and subsequent codes from thematic analysis. Results: We screened 1775 articles and extracted qualitative data from 12. The qualitative data revealed 20 factors unique to hemodialysis across the World Health Organization's five dimensions of adherence. Additionally, two overarching themes emerged from the data: (1) adherence in the context of patients' whole lives and (2) dialysis treatment as a double-edged sword. Patient-level factors reflected in the qualitative data extended beyond knowledge about hemodialysis treatment or motivation to adhere to treatment. Patients described a profound grieving process over loss of their "old self" that impacted adherence. They also navigated complex challenges that could be exacerbated by social determinants of health as they balanced treatment, life tasks, and social roles. Conclusions: This review adds to the growing evidence that one-size-fits-all approaches to improving adherence among patients on hemodialysis are inadequate. Adherence may improve when routine care incorporates patient context and provides ongoing support to patients and families as they navigate the logistical, physical, and psychological hardships of living with dialysis. New research is urgently needed to guide a change in course.

Mapping the Transcriptome Underpinning Acute Corticosteroid Action within the Cortical Collecting Duct

mkm27@st-andrews.ac.uk — Tue, 08 Nov 2022 12:15:01 GMT-08:00

Background Corticosteroids regulate distal nephron and collecting duct Na+ reabsorption, contributing to fluid-volume and blood pressure homeostasis. The transcriptional landscape underpinning the acute stimulation of the epithelial sodium channel (ENaC) by physiological concentrations of corticosteroids remains unclear. Methods Transcriptomic profiles underlying corticosteroid-stimulated ENaC activity in polarised mCCDcl1 cells were generated by coupling electrophysiological measurements of amiloride-sensitive currents with RNAseq. Generation of a collecting-duct specific reporter mouse line, mT/mG-Aqp2Cre, enabled isolation of primary collecting duct cells by FACS and ENaC activity was measured in cultured primary cells following acute application of corticosteroids. Expression of target genes was assessed by qRT-PCR in cultured cells or freshly isolated cells following acute elevation of steroid hormones in mT/mG-Aqp2Cre mice. Results Physiological relevance of the mCCDcl1 model was confirmed with aldosterone-specific stimulation of SGK1 and ENaC activity. Corticosterone only modulated these responses at supraphysiological concentrations or when 11βHSD2 was inhibited. When 11βHSD2 protection was intact, corticosterone caused no significant change in transcripts. We identified a small number of aldosterone-induced transcripts associated with stimulated ENaC activity in mCCDcl1 cells and a much larger number with corticosterone in the absence of 11βHSD2 activity. Cells isolated from mT/mG-Aqp2Cre mice were validated as collecting duct-specific and assessment of identified aldosterone-induced genes revealed that Sgk1, Zbtbt16, Sult1d1, Rasd1 and Gm43305 are acutely upregulated by corticosteroids both in vitro and in vivo. Conclusions This study reports the transcriptome of mCCDcl1 collecting duct cells and identifies a small number of aldosterone-induced genes associated with acute stimulation of ENaC, including 3 previously undescribed genes.

A machine learning model to predict diuretic resistance

jomercier@nosm.ca — Tue, 08 Nov 2022 09:30:45 GMT-08:00

Background: Volume overload is a common complication encountered in hospitalized patients, and the mainstay of therapy is diuresis. Unfortunately, the diuretic response in some individuals is inadequate despite a typical dose of loop diuretics, a phenomenon called diuretic resistance. An accurate prediction model that predicts diuretic resistance using pre-dosing variables could inform the right diuretic dose for a prospective patient. Methods: Two large, deidentified, publicly available and independent ICU databases from the United States were used - The Medical Information Mart for Intensive Case III (MIMIC) and the Philips eICU databases. Loop diuretic resistance was defined as less than 1400cc of urine per 40mg of diuretic dose in 24hrs. Using 24-hour windows throughout admission, commonly accessible were obtained and incorporated into the model. Data imputation was performed using a highly accurate Machine Learning method. Using XGBoost, several models were created using train and test datasets from the eICU database. These were then combined into an ensemble model optimized for increased specificity and then externally validated on the MIMIC database. Results: The final ensemble model was composed of four separate models, each using 21 commonly available variables. The ensemble model outperformed individual models during validation. Higher serum creatinine, lower systolic blood pressure, lower serum chloride, higher age, and female sex were the most important predictors of diuretic resistance (in that order). The specificity of the model on external validation was 92% yielding a positive likelihood ratio of 3.46 while maintaining overall discrimination (C-statistic 0.69). Conclusions: A diuretic resistance prediction model was created using machine learning and was externally validated in ICU populations. The model is easy to use, would provide actionable information at the bedside, and would be ready for implementation in existing electronic medical records. This study also provides a framework for the development of future Machine Learning models.

Intraoperative Urine Oxygen in Cardiac Surgery and 12-Month Outcomes

samuelparry10@gmail.com — Tue, 08 Nov 2022 09:30:45 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Global Dialysis Perspective: Georgia

irma.tchokhonelidze@gmail.com — Tue, 08 Nov 2022 08:17:36 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Accepting Living Kidney Donors with Preexisting Diabetes Mellitus

Soliman, Karim M. — Tue, 11 Oct 2022 09:23:53 GMT-07:00

Decay-Accelerating Factor Expression Modulates the Severity of Experimental Focal Segmental Glomerulosclerosis

sofia.bin@mssm.edu — Mon, 07 Nov 2022 01:31:15 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Toxic Occupational Exposures and Membranous Nephropathy

Cremoni, Marion — Tue, 25 Oct 2022 08:17:22 GMT-07:00

Processes of Care in Survivors of Acute Kidney Injury followed in Specialized Postdischarge Clinics

Ortiz-Soriano, Victor — Thu, 25 Aug 2022 10:44:55 GMT-07:00

A Qualitative Content Analysis of Comments on Press Articles on Deemed Consent for Organ Donation in Canada

Fox, Danielle E. — Wed, 26 Oct 2022 09:16:54 GMT-07:00

Integrating PROMs in Routine Dialysis Care

Flythe, Jennifer E. — Tue, 25 Oct 2022 08:34:20 GMT-07:00

Understanding Public Perspectives on Opt-Out Deceased Donor Transplant Policy

Butler, Catherine R. — Wed, 26 Oct 2022 10:18:29 GMT-07:00

Can We Turn the Symptom Curve?

Rodriguez de Sosa, Giselle — Fri, 28 Oct 2022 06:50:05 GMT-07:00

Correction: Physiology of the Aging Kidney: We Know Where We Are Going, but We Don’t Know How…

American Society of Nephrology — Tue, 20 Sep 2022 06:25:14 GMT-07:00

Five-Year Symptom Trajectories in Nondialysis-Dependent CKD Patients

Faye, Moustapha — Fri, 28 Oct 2022 06:50:05 GMT-07:00

“Make Me a Match”

Cheng, Steven C. — Tue, 19 Jul 2022 11:18:54 GMT-07:00

Acute Kidney Injury in Patients with Liver Disease

Cullaro, Giuseppe — Thu, 28 Jul 2022 06:55:06 GMT-07:00

AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C–associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.

How the Routine Use of Patient-Reported Outcome Measures for Hemodialysis Care Influences Patient-Clinician Communication

Schick-Makaroff, Kara — Tue, 25 Oct 2022 08:17:23 GMT-07:00

Genome-Wide Association Study for eGFR in a Taiwanese Population

Chen, Ying-Chun — Wed, 12 Oct 2022 05:31:22 GMT-07:00

Gut Microbiome and Kidney Disease

Shankaranarayanan, Divya — Wed, 06 Jul 2022 08:19:46 GMT-07:00

Safety and Efficacy of Belimumab in Patients with Lupus Nephritis

Furie, Richard — Thu, 27 Oct 2022 06:45:15 GMT-07:00

The Role of Anti-B Cell Activating Factor Therapy for Treating Lupus Nephritis

Wooden, Benjamin — Thu, 27 Oct 2022 07:09:30 GMT-07:00

Digenic Alport Syndrome

Savige, Judy — Wed, 08 Jun 2022 05:51:16 GMT-07:00

Digenic Alport syndrome refers to the inheritance of pathogenic variants in COL4A5 plus COL4A3 or COL4A4 or in COL4A3 plus COL4A4. Where digenic Alport syndrome includes a pathogenic COL4A5 variant, the consequences depend on the sex of the affected individual, COL4A5 variant “severity,” and the nature of the COL4A3 or COL4A4 change. A man with a pathogenic COL4A5 variant has all his collagen IV α3α4α5-heterotrimers affected, and an additional COL4A3 or COL4A4 variant may not worsen disease. A woman with a pathogenic COL4A5 variant has on average 50% of her heterotrimers affected, which is increased to 75% with a further COL4A3 or COL4A4 variant and associated with a higher risk of proteinuria. In digenic Alport syndrome with pathogenic COL4A3 and COL4A4 variants, 75% of the heterotrimers are affected. The COL4A3 and COL4A4 genes occur head-to-head on chromosome 2, and inheritance is autosomal dominant when both variants affect the same chromosome (in cis) or recessive when they affect different chromosomes (in trans). This form of digenic disease results in increased proteinuria and a median age of kidney failure intermediate between autosomal dominant and autosomal recessive Alport syndrome. Previous guidelines have suggested that all pathogenic or likely pathogenic digenic variants should be identified and reported. Affected family members should be identified, treated, and discouraged from kidney donation. Inheritance within a family is easier to predict if the two variants are considered independently and if COL4A3 and COL4A4 variants are known to be inherited on the same or different chromosomes.

Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria

Heerspink, Hiddo J.L. — Fri, 09 Sep 2022 01:31:57 GMT-07:00

Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation

Dandamudi, Raja — Thu, 27 Oct 2022 06:45:14 GMT-07:00

How I Treat Steroid-Sensitive Nephrotic Syndrome in Children

Vivarelli, Marina — Fri, 02 Sep 2022 08:49:13 GMT-07:00

Reducing the Risks of Home Dialysis Innovation and Uptake

Cahill, Zachary — Fri, 12 Aug 2022 11:11:52 GMT-07:00

Media Analysis of the Canadian Deemed Consent Policy

Conway, Paul T. — Wed, 26 Oct 2022 09:16:54 GMT-07:00

Characterization of Glomerular and Tubulointerstitial Proteomes in a Case of NSAID-Attributed Acute Kidney Injury

samir.parikh@osumc.edu — Mon, 07 Nov 2022 09:50:01 GMT-08:00

The major goals of the Kidney Precision Medicine Project (KPMP) are to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of chronic kidney disease and acute kidney injury. In this clinical-pathological-molecular correlation, we describe the case of a 38-year-old woman without any prior history of chronic kidney disease who underwent a research kidney biopsy in the setting of acute kidney injury suspected to be due to non-steroidal anti-inflammatory use following cesarean section delivery. The participant's histopathology was consistent with mild acute tubular injury, without significant interstitial fibrosis or tubular atrophy. This diagnosis was supported by analysis of the glomerular and tubulointerstitial proteomes. The proteomic interrogation revealed a molecular landscape that demonstrated differences in kidney prostaglandin synthesis that may be in response to NSAIDs, as well as signs of intra-renal inflammation and fibrosis that were not evident by histopathology alone.

Global Perspectives in Acute Kidney Injury: Bolivia

rclaure@yahoo.com — Mon, 07 Nov 2022 09:33:24 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it.

Organizing Nephrologists at the State Level

droth@med.miami.edu — Mon, 07 Nov 2022 08:37:58 GMT-08:00

Can Kidney Organoid Xenografts Accelerate Therapeutic Development for Genetic Kidney Disorders?

Kuo, Ting-Chun — Mon, 07 Nov 2022 05:46:13 GMT-08:00

A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content. The improvements can translate into more accurate representations of disease phenotypes and mechanisms in vivo. Recent studies using kidney organoid xenografts highlighted the unique potential of this novel methodology for elucidating molecular mechanisms driving monogenic kidney disorders and for the development ofnovel pharmacotherapies.

Management of Patients with Kidney Failure and Pericarditis

Rosen, Raphael J. — Thu, 03 Nov 2022 07:23:11 GMT-07:00

Nuclear Magnetic Resonance Metabolomic Profiling and Urine Chemistries in Incident Kidney Stone Formers Compared with Controls

Thongprayoon, Charat — Tue, 19 Jul 2022 11:52:26 GMT-07:00

Anti-Neu5Gc Antibodies do not Affect Response to Human or Chimeric Monoclonal Anti-CD20 Antibodies in Children with Nephrotic Syndrome

Angeletti, Andrea — Tue, 23 Aug 2022 02:09:48 GMT-07:00

Financial Barriers to the Optimal Use of Peritoneal Dialysis in France and Europe, as in the United States

Rostoker, Guy — Tue, 30 Aug 2022 07:22:48 GMT-07:00

The ABCD of Kidney Allograft Pathology—The Beginning of the Beginning

Muthukumar, Thangamani — Mon, 10 Oct 2022 10:09:16 GMT-07:00

Climate and the Nephrologist

Young, Sarah E. — Tue, 01 Nov 2022 07:35:13 GMT-07:00

Climate change is upon us, and it will have a major effect on both kidney disease and the nephrology practice. But the converse is also true: our treatment of kidney disease has an effect on the climate. Much attention has focused on how rising temperatures can lead to acute and CKD and health exacerbations in patients with established kidney disease. Climate change is also associated with rising air pollution from wildfires and industrial wastes and infectious diseases associated with flooding and changing habitats, all of which heighten the risk of acute and CKD. Less well recognized or understood are the ways nephrology practices, in turn, contribute to still more climate change. Hemodialysis, although lifesaving, can be associated with marked water usage (up to 600 L per dialysis session), energy usage (with one 4-hour session averaging as much as one fifth of the total energy consumed by a household per day), and large clinical wastes (with hemodialysis accounting for one third of total clinical medicine–associated waste). Of note, >90% of dialysis occurs in highly affluent countries, whereas dialysis is much less available in the poorer countries where climate change is having the highest effect on kidney disease. We conclude that not only do nephrologists need to prepare for the rise in climate-associated kidney disease, they must also urgently develop more climate-friendly methods of managing patients with kidney disease.

Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies

Vaulet, Thibaut — Wed, 07 Sep 2022 10:49:37 GMT-07:00

A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis

Kaplan, Jennifer M. — Thu, 18 Aug 2022 07:51:16 GMT-07:00

Centering Anti-Racism and Social Justice in Nephrology Education to Advance Kidney Health Equity

Purnell, Tanjala S. — Fri, 09 Sep 2022 08:50:58 GMT-07:00

Is Home Dialysis the Way Forward for Medicare? Assessing Potential Cost Savings Associated with Peritoneal Dialysis

Tummalapalli, Sri Lekha — Wed, 12 Oct 2022 11:47:37 GMT-07:00

Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity

Sun, Zeguo — Tue, 30 Aug 2022 07:22:48 GMT-07:00

Early Molecular Events Mediating Loss of Aquaporin-2 during Ureteral Obstruction in Rats

Sung, Chih-Chien — Tue, 02 Aug 2022 12:56:00 GMT-07:00

Differences in Phosphate and Parathyroid Hormone Concentrations over the Day among Patients on Hemodialysis

Ginsberg, Charles — Wed, 17 Aug 2022 07:50:34 GMT-07:00

A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2

Hada, Ichiro — Fri, 19 Aug 2022 10:51:52 GMT-07:00

Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True

Zhang, Ping L. — Fri, 09 Sep 2022 08:51:00 GMT-07:00

Authors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True

Shin, Naomi S. — Fri, 09 Sep 2022 08:50:59 GMT-07:00

Is it Time to Re-Evaluate Our Experimental Approach to Studying Diffuse Podocytopathies?

Watts, Andrew J.B. — Thu, 22 Sep 2022 11:39:27 GMT-07:00

This Month's Highlights

American Society of Nephrology — Mon, 31 Oct 2022 10:00:25 GMT-07:00

Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD

Jongs, Niels — Wed, 17 Aug 2022 09:37:29 GMT-07:00

Hypoxia-Inducible Factor–Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs?

Locatelli, Francesco — Tue, 30 Aug 2022 11:12:10 GMT-07:00

Anemia is a common complication of chronic kidney disease; it is mainly treated with erythropoiesis-stimulating agents (ESAs) and iron. Experimental studies extensively investigated the mechanisms involved in the body’s response to hypoxia and led to the discovery of the hypoxia-inducible factor (HIF) pathway and the enzymes regulating its function. HIF-prolyl-hydroxyl domain (PHD) inhibitors are a new class of oral drugs developed to treat anemia in chronic kidney disease. By inhibiting the function of PHD enzymes, they mimic the exposure to moderate hypoxia and stimulate the production of endogenous erythropoietin and very likely increase iron availability. Some data also suggest that their efficacy and, consequently, dose needs are less influenced by inflammation than ESAs. Overall, data from phases 2 and 3 clinical development showed efficacy in anemia correction and maintenance for all of the class molecules compared with placebo (superiority) or erythropoiesis-stimulating agents (noninferiority). Three molecules, roxadustat, vadadustat, and daprodustat, underwent extensive clinical investigation to assess their safety on hard cardiovascular end points, mortality, and special interest events (including cancer and thrombosis). Aside from vadadustat in the nondialysis population, at the prespecified primary analyses, all three molecules met the noninferiority margin for the risk of major cardiovascular events compared with erythropoiesis-stimulating agents or placebo. The reason for this discrepancy is difficult to explain. Other safety signals came from secondary analyses of some of the other randomized clinical trials, including a higher incidence of thrombosis. A more extensive clinical experience with post-marketing data on hard safety issues is needed to define better when and how to use HIF-PHD inhibitors compared with already available ESAs.

Steroid-Resistant Nephrotic Syndrome–Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and Activity

Liu, Pei-Ju — Fri, 09 Sep 2022 08:50:58 GMT-07:00

Translation Rescue by Targeting Ppp1r15a through Its Upstream Open Reading Frame in Sepsis-Induced Acute Kidney Injury in a Murine Model

Kidwell, Ashley — Tue, 25 Oct 2022 10:46:47 GMT-07:00

Effects of vitamin D3 supplementation on cardiovascular and cancer outcomes by eGFR in VITAL

climonte@uw.edu — Mon, 31 Oct 2022 06:43:44 GMT-07:00

Background: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000IU vitamin D3 and/or 1g omega-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study endpoints were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results: Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years and 51% were female. Vitamin D3 resulted in higher serum 25(OH)D compared to placebo (difference in change 12.5 [95%CI 12.0,13.1] ng/mL), without heterogeneity by eGFR (p-interaction, continuous eGFR=0.20). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (p-interaction=0.048): -6.9 (95% CI -10.5,-3.4) , -5.8 (-8.3,-3.4), -4.0 (-5.9,-2.2), and -3.8 (-5.6,-2.0) pg/mL for eGFR <60, 60-74, 75-89, and >90 ml/min/1.73m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (p-interaction=0.61) and cancer (p-interaction=0.89) did not differ by eGFR: HR (95% CI) 1.14 (0.73,1.79), 1.06 (0.75,1.50), 0.92 (0.67,1.25), and 0.92 (0.66,1.27), across eGFR categories for cardiovascular events and 1.63 (1.03,2.58), 0.85 (0.64,1.11), 0.84 (0.68,1.03), and 1.11 (0.92,1.35) for cancer, respectively. Conclusions: We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite impacts on 25(OH)D and PTH concentrations.

Heme Protein-Induced Acute Kidney Injury is caused by Disruption of Mitochondrial Homeostasis in Proximal Tubular Cells

christof.westenfelder@hsc.utah.edu — Mon, 31 Oct 2022 06:43:44 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Baroreceptor Sensitivity in Individuals with Chronic Kidney Disease and Heart Failure

david.charytan@nyulangone.org — Fri, 28 Oct 2022 01:14:26 GMT-07:00

Background: Heart failure is the most common cardiovascular complication of chronic kidney disease and foreshadows high morbidity and mortality. Baroreflex impairment likely contributes to the cardiovascular mortality. We aimed to study the associations between chronic kidney disease, heart failure and baroreflex sensitivity (BRS) as well as their association with cardiovascular outcomes Methods: We analyzed data from a previously recruited cohort study which included 247 individuals with moderate-to-severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography and laboratory measurements. We used logistic regression models to assess the association of CKD with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality Results: Median eGFR among individuals with CKD was 52 (IQR 44-56) mL/min/1.73m2 eGFR was lower in those with depressed BRS (65 IQR 54-76 mL/min/1.73m2) compared to those with preserved BRS (73 IQR 64-87 mL/min/1.73m2, P=<0.001). The majority of individuals with CKD had depressed BRS compared to those without CKD (60.3% vs. 29.1%, P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared to those with preserved BRS and CKD. Conclusions: Cardiac BRS is depressed in patients with CKD and HF and may be an important contributor to cardiovascular mortality.

In-Hospital Prescription Checking System for Hospitalized Patients with Decreased Glomerular Filtration Rate

Sonoda, Akihiro — Fri, 08 Jul 2022 11:22:33 GMT-07:00

Percutaneous Ultrasound-Guided Kidney Transplant Biopsy Outcomes: From the Nephrologist to the Radiologist Standpoint

Mattiazzi, Adela D. — Tue, 23 Aug 2022 01:04:45 GMT-07:00

AKI in a Patient with Myelodysplastic Syndrome and Dark Urine

Isobe, Shinsuke — Thu, 27 Oct 2022 08:30:18 GMT-07:00

A Pilot Randomized Controlled Trial of Integrated Palliative Care and Nephrology Care

Scherer, Jennifer S. — Fri, 12 Aug 2022 01:43:15 GMT-07:00

A Nomogram to Identify Hyperkalemia Risk in Patients with Advanced CKD

Xue, Cheng — Tue, 20 Sep 2022 06:14:45 GMT-07:00

Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: CON

Rodby, Roger A. — Tue, 15 Feb 2022 09:28:57 GMT-08:00

Correction of Vascular Calcification and Hyperphosphatemia in CKD Rats Treated with ASARM Peptide

Rowe, Peter S. — Tue, 30 Aug 2022 09:39:36 GMT-07:00

The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study

Vinson, Amanda J. — Tue, 28 Jun 2022 11:23:09 GMT-07:00

Association of Pre-Transplant C-Peptide with Post-Transplant Diabetes: A New Approach to Identifying High-Risk Patients?

Joachim, Emily — Thu, 27 Oct 2022 08:30:18 GMT-07:00

Clinical Decision Support Tools for Reduced and Changing Kidney Function

Schreier, Diana J. — Thu, 27 Oct 2022 08:30:18 GMT-07:00

Global Perspective on Kidney Transplantation: Ecuador

Jiménez, Darío — Fri, 22 Jul 2022 01:35:59 GMT-07:00

ESKD in a Young Patient with Chronic Bilateral Flank Pain

Merchant, Asad A. — Thu, 27 Oct 2022 08:30:18 GMT-07:00

Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: PRO

Obaidi, Zainab — Tue, 15 Feb 2022 09:28:57 GMT-08:00

The Transplant Kidney Biopsy: In Whose Hands?

Virmani, Sarthak — Thu, 27 Oct 2022 08:30:18 GMT-07:00

The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

Campbell, Nathan E. — Fri, 12 Aug 2022 01:43:15 GMT-07:00

Preeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, PE has no cure beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation; intrauterine growth restriction; uterine artery resistance; dysregulation of the renin-angiotensin system. Which contributes to renal dysfunction; and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling, resulting in decreased placental perfusion and thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in proinflammatory and anti-inflammatory cell types in women with PE and in animal models used to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases, such as cardiovascular disease, CKD, dementia during the postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.

Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes

Lizotte, Farah — Wed, 31 Aug 2022 12:01:56 GMT-07:00

Innate Immunity and SARS-CoV-2 Vaccine Response in Hemodialysis Patients

Valentini, Nicolas — Wed, 10 Aug 2022 01:41:42 GMT-07:00

International Practices on COVID-19 Vaccine Mandates for Transplant Candidates

Caliskan, Yasar — Mon, 15 Aug 2022 01:52:02 GMT-07:00

Advantages, Limitations, and Clinical Considerations in Using Cystatin C to Estimate GFR

Chen, Debbie C. — Tue, 23 Aug 2022 01:04:45 GMT-07:00

Cystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making. In the efforts to remove race from eGFR calculations in the United States, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Joint Task Force recommended increasing availability and clinical adoption of cystatin C to assess kidney function. This review summarizes the key advantages and limitations of cystatin C use in clinical practice. Our goals were to review and discuss the literature on cystatin C; understand the evidence behind the recommendations for its use as a marker of kidney function to diagnose CKD and risk stratify patients for adverse outcomes; discuss the challenges of its use in clinical practice; and guide clinicians on its interpretation.

Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: COMMENTARY

Brewster, Ursula C. — Tue, 15 Feb 2022 09:28:57 GMT-08:00

Peritoneal Dialysis Adequacy: Too Much of a Good Thing?

Tillquist, Kristen — Fri, 26 Aug 2022 09:06:35 GMT-07:00

Biomarkers for Early Diagnosis of AKI: Could It Backfire?

Claure-Del Granado, Rolando — Thu, 08 Sep 2022 01:21:41 GMT-07:00

Apixaban versus No Anticoagulation by P2Y12 Inhibitor Prescription Status in Dialysis Patients with Atrial Fibrillation

Mavrakanas, Thomas A. — Mon, 01 Aug 2022 01:21:41 GMT-07:00

How to Determine Fluid Management Goals during Continuous Kidney Replacement Therapy in Patients with AKI: Focus on POCUS

Beaubien-Souligny, William — Tue, 19 Jul 2022 01:29:42 GMT-07:00

The utilization of kidney replacement therapies (KRT) for fluid management of patients who are critically ill has significantly increased over the last years. Clinical studies have suggested that both fluid accumulation and high fluid removal rates are associated with adverse outcomes in the critically ill population receiving KRT. Importantly, the ideal indications and/or fluid management strategies that could favorably affect these patients are unknown; however, differentiating clinical scenarios in which effective fluid removal may provide benefit to the patient by avoiding congestive organ injury, compared with other settings in which this intervention may result in harm, is direly needed in the critical care nephrology field. In this review, we describe observational data related to fluid management with KRT, and examine the role of point-of-care ultrasonography as a potential tool that could provide physiologic insights to better individualize decisions related to fluid management through KRT.

When a Kidney Doctor Becomes a Kidney Donor

Djamali, Arjang — Mon, 01 Aug 2022 01:21:41 GMT-07:00

Prominent Mitochondrial Injury as an Early Event in Heme Protein-Induced Acute Kidney Injury

Singh, Raman Deep — Mon, 15 Aug 2022 01:52:02 GMT-07:00

The New Kidney-Focused Companies: A Privatized Approach to Value-Based Care and Addressing Social Determinants of Health

Lin, Eugene — Thu, 27 Oct 2022 06:46:11 GMT-07:00

Interferon Gamma contributes to the immune mechanisms of hypertension

SMu@uams.edu — Wed, 26 Oct 2022 02:03:07 GMT-07:00

Hypertension is the leading cause of cardiovascular disease and the primary risk factor for mortality worldwide. For over half a century, researchers have demonstrated that the immunity plays an important role in the development of hypertension; however, the precise mechanisms are still under investigation. The current body of knowledge indicates that pro-inflammatory cytokines may play an important role in contributing to immune-related pathogenesis of hypertension. Interferon gamma (IFNγ), in particular, as an important cytokine that modulates immune responses, has been recently identified as an critical regulator of blood pressure by several groups including us. In this review, we focus on exploring the role of IFNγ in contributing to the pathogenesis of hypertension, outlining the various immune producers of this cytokine and described signaling mechanisms involved. We demonstrate a key role for IFNγ in hypertension through global knockout studies and related downstream signaling pathways that IFNγ production from CD8+ T cell (CD8T) in the kidney promoting CD8T-stimulated salt retention via renal tubule cells, thereby exacerbating hypertension. We discuss potential activators of these T cells described by the current literature and relay a novel hypothesis for activation.

Testican-2 is Associated with Reduced Risk of Incident ESKD

dwen@bwh.harvard.edu — Wed, 26 Oct 2022 11:48:08 GMT-07:00

Background: Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with estimated glomerular filtration rate (eGFR) and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of end stage kidney disease (ESKD) is unknown. Methods: Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n=703), the Chronic Renal Insufficiency Cohort (CRIC) study (n=3,196), and the Atherosclerosis Risk in Communities (ARIC) study (n=4,378). We compared baseline characteristics by testican-2 tertile and used Cox proportional hazards models to study the association of testican-2 with incident ESKD. Results: Higher testican-2 levels were associated with higher measured GFR (mGFR) in AASK, higher eGFR in the CRIC and ARIC studies, and lower albuminuria in all cohorts. Baseline testican-2 levels were significantly associated with incident ESKD in Cox proportional hazards models adjusted for age, sex, and race (Model 1) and Model 1 + mGFR or eGFR + comorbidities (Model 2). In Model 3 (Model 2 + proteinuria), the associations between testican-2 (per SD increase) and incident ESKD were: AASK (HR = 0.84 [0.72, 0.98], P = 0.023), CRIC (HR = 0.95 [0.89, 1.02], P = 0.14), ARIC (HR = 0.54 [0.36, 0.83], P = 0.0044), and meta-analysis (HR = 0.92 [0.86, 0.98], P = 0.0073). Conclusions: Across three cohorts spanning >8,000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD.

Distinguishing among HCO3−, CO3=, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Lee, Seong-Ki — Wed, 26 Oct 2022 08:26:35 GMT-07:00

Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor

Bahena-Lopez, Jessica Paola — Wed, 07 Sep 2022 10:49:37 GMT-07:00

Sweet-Talking the Distal Nephron Calcium-Sensing Receptor

Subramanya, Arohan R. — Wed, 26 Oct 2022 08:26:34 GMT-07:00

Basic Requirements for Improving Home Dialysis Utilization: Specialty Nephrology Care and Pre-End Stage Kidney Disease Education

ashutosh.shukla@medicine.ufl.edu — Tue, 25 Oct 2022 10:46:47 GMT-07:00

XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in Mice

Krappitz, Matteus — Fri, 21 Oct 2022 06:17:47 GMT-07:00

Relationship of kidney tubule biomarkers with cognition among community-living elders in the Health ABC Study

lmmiller@health.ucsd.edu — Thu, 20 Oct 2022 11:55:33 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Kidney-Protective Effects of SGLT2 Inhibitors

Palmer, Biff F. — Tue, 11 Oct 2022 09:23:53 GMT-07:00

The sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral part of clinical practice guidelines to slow the progression of CKD in patients with and without diabetes mellitus. Although initially developed as antihyperglycemic drugs, their effect on the kidney is multifactorial resulting from profuse glycosuria and natriuresis consequent to their primary site of action. Hemodynamic and metabolic changes ensue that mediate kidney-protective effects, including (1) decreased workload of proximal tubular cells and prevention of aberrant increases in glycolysis, contributing to a decreased risk of AKI; (2) lowering of intraglomerular pressure by activating tubular glomerular feedback and reductions in BP and tissue sodium content; (3) initiation of nutrient-sensing pathways reminiscent of starvation activating ketogenesis, increased autophagy, and restoration of carbon flow through the mitochondria without production of reactive oxygen species; (4) body weight loss without a reduction in basal metabolic rate due to increases in nonshivering thermogenesis; and (5) favorable changes in quantity and characteristics of perirenal fat leading to decreased release of adipokines, which adversely affect the glomerular capillary and signal increased sympathetic outflow. Additionally, these drugs stimulate phosphate and magnesium reabsorption and increase uric acid excretion. Familiarity with kidney-specific mechanisms of action, potential changes in kidney function, and/or alterations in electrolytes and volume status, which are induced by these widely prescribed drugs, will facilitate usage in the patients for whom they are indicated.

Genetic testing in nephrology: Show your pedigree!

francesca.becherucci@meyer.it — Wed, 19 Oct 2022 04:33:59 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Role of GSTM1 in hypertension, chronic kidney disease and related diseases across the lifespan

Thu_Le@URMC.Rochester.edu — Wed, 19 Oct 2022 04:33:59 GMT-07:00

Over twenty years after the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, chronic kidney disease (CKD) remains a major public health burden with very limited therapeutic options to halt or slow kidney disease progression at all ages. The general consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD. Understanding the specific pathophysiologic mechanisms in those who are genetically most susceptible to oxidative stress is a crucial step to inform therapy in an individualized medicine approach, taking into account differing exposures and risks across the lifespan. GSTM1 (glutathione-S-transferase mu 1) is a phase II enzyme involved in inactivation of reactive oxygen species and metabolism of xenobiotics. In particular, those with the highly prevalent GSTM1 null genotype (GSTM1(0/0)) may be more susceptible to kidney disease progression due to impaired capacity to handle the increased oxidative stress burden in disease states and might specifically benefit from therapy that targets the redox imbalance mediated by loss of GSTM1 enzyme. In this review, we will discuss the studies implicating the role of GSTM1 deficiency in kidney and related diseases from experimental rodent models to humans, from the prenatal period through senescence, and the potential underlying mechanism.

The Cleveland Clinic Kidney Biopsy Epidemiological Project

bobarts@ccf.org — Wed, 19 Oct 2022 04:33:59 GMT-07:00

Background: The kidney biopsy is the gold standard for the diagnosis of glomerular diseases. Large-scale, epidemiological studies describing the prevalence of kidney diseases are lacking especially in the US. We aimed to determine the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. Methods: We identified all patients with a native kidney biopsy performed/reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, gender, race and location to determine epidemiological trends. Results: Of over 9600 patients, we excluded transplant/donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46.2% female patients. Self-reported racial demographics included 72.9% White, 21.7% Black, 3.1% multi-racial, and 1.6% Asian background, with 5.1% Hispanic. Common diagnoses were: FSGS (n=633, 15.3%), diabetic kidney disease (DKD) (n=602, 14.6%), IgA nephropathy (n=319, 7.7%), lupus nephritis (LN) (n=289, 7.0%), pauci-immune glomerulonephritis (n=275, 6.7%), membranous nephropathy (n=211, 5.1%), and amyloidosis (n=110, 2.7%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those over 70 years were more likely to have FSGS, while those less than 45 years were more likely to have IgA Nephropathy or LN. Males were more likely to have FSGS or IgAN and less likely to have LN. Blacks were more likely to have FSGS, DKD or LN. Hispanics were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum prior to and during the COVID 19 pandemic. Conclusion: Our study catalogues the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.

Cardiac manifestations in patients with autosomal polycystic kidney disease (ADPKD) - a single-center study

roman-ulrich.mueller@uk-koeln.de — Tue, 18 Oct 2022 02:17:49 GMT-07:00

Background: ADPKD is the most common monogenetic kidney disease and results in kidney failure in over 75% of affected individuals. As a systemic disorder, ADPKD is associated with a variety of extrarenal manifestations affecting the majority of patients including cardiac manifestations. We characterized the cardiac involvement in ADPKD patients from the German AD(H)PKD registry and compared them to kidney donor candidates as controls. Methods: In this single-center cohort study, we evaluated 141 ADPKD (44.17 ± 11.23 years) patients from the German AD(H)PKD registry and 60 kidney donor candidates (55.08 ± 10.21 years). All patients underwent clinical examination, abdominal MRI, and transthoracic echocardiography. Results: 65% of ADPKD patients showed hypertrophy of the left ventricle (as defined by an end-diastolic left ventricular septal wall thickness (IVSd) greater than 10mm) compared to 55% in control patients. Mitral regurgitation was the most common finding among 53.57 % of ADPKD patients who exhibited valvular dysfunction, albeit mild in the majority of patients. Interestingly, left ventricular ejection fraction (LV-EF) differed significantly between both groups with higher values in ADPKD patients (63.53±6.38% vs. 60.21±5.72%), while other parameters including IVSd, left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE) and pressure gradients across the aortic and tricuspid valve were similar between groups. Correlations of echocardiographic parameters with markers of disease progression revealed statistically significant associations for aortic root diameter (p = 0.014), the pressure gradient across the aortic valve (AV dPmax) (p = 0.0003) and left ventricular septal wall thickness (IVSd) (p = 0.0001), indicating that rapid kidney disease progression may also be associated with cardiac findings. Conclusion: Cardiovascular abnormalities are prevalent in ADPKD patients. Considering the importance of cardiovascular disease for outcome in CKD, early management and possibly prevention are important goals of any treatment scheme. Consequently, echocardiography should be offered to all ADPKD patients in routine management.

Urinary Citrate is Associated with Kidney Outcomes in Early Polycystic Kidney Disease

ita.heilberg@gmail.com — Mon, 17 Oct 2022 01:50:35 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Environmental Exposures and Kidney Diseases

abhijit_kshirsagar@med.unc.edu — Mon, 17 Oct 2022 01:50:35 GMT-07:00

Accumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants such as trace elements, per- and polyfluorooakyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence which at present relies heavily on observational studies and animal models, and propose using recently developed quantitative methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.

Ratio Profile: Physiologic Approach to Estimating Appropriate IV Fluid Rate to Manage Hyponatremia of SIAD

shelchen@yahoo.com — Mon, 17 Oct 2022 05:55:39 GMT-07:00

A hyponatremic patient with the syndrome of inappropriate antidiuresis (SIAD) gets normal saline (NS), and the plasma sodium decreases, paradoxically. To explain, desalination is often invoked: If urine is more concentrated than NS, the fluid's salts are excreted while some water is reabsorbed, exacerbating hyponatremia. But comparing concentrations can be deceiving. They should be converted to quantities, as mass balance is key to unlocking the paradox. The [sodium] equation can legitimately be used to track all of the sodium, potassium, and water entering and leaving the body. Each input or output "module" can be counterbalanced by a chosen IV fluid so that the plasma sodium stays stable. This equipoise is expressed in terms of the IV fluid's infusion rate, an easy calculation called the ratio profile. Knowing the infusion rate that maintains steady state, we can prescribe the IV fluid at a faster rate in order to raise the plasma sodium. Rates less than the ratio profile may risk a paradox, which essentially is caused by an IV fluid underdosing. Selecting an IV fluid that is more concentrated than urine is not enough to prevent paradoxes; even 3% saline can be underdosed. Water drinking adds to the ratio profile and is underestimated in its ability to provoke a paradox. In conclusion, the quantitative approach demystifies the paradoxical worsening of hyponatremia in SIAD and offers a prescriptive guide to keep the paradox from happening. The ratio profile method is objective and quickly deployable on rounds, where it may change patient management for the better.

Global Dialysis Perspectives: Ecuador

cristobalsantacruz@yahoo.com — Mon, 17 Oct 2022 05:55:39 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis Patients

Kurella Tamura, Manjula — Wed, 14 Sep 2022 06:12:18 GMT-07:00

Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems

An, Jaejin — Fri, 09 Sep 2022 06:28:58 GMT-07:00

Resistant Hypertension in Chronic Kidney Disease

Shulman, Rachel — Fri, 09 Sep 2022 07:02:26 GMT-07:00

Associations of COVID-19 Outcomes with Dialysis Modalities and Settings

Weinhandl, Eric D. — Thu, 08 Sep 2022 08:07:15 GMT-07:00

How maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19–related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020–2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%–60% lower odds of all events during weeks 12–23 of 2020; 24%–37% lower odds of all events during weeks 24–37 of 2020; 20%–33% lower odds of infection and hospitalization during the winter of 2020–2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%–1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.

Drug Development for Cystic Kidney Diseases

Fedeles, Sorin — Tue, 23 Aug 2022 12:00:26 GMT-07:00

Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis

Richardson, Michelle M. — Tue, 15 Mar 2022 08:22:04 GMT-07:00

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping–specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.

Point-of-Care Ultrasound Training during Nephrology Fellowship

Moore, Catherine A. — Wed, 21 Sep 2022 10:43:19 GMT-07:00

Perspectives on Drug Development in Autosomal Recessive Polycystic Kidney Disease

Liebau, Max C. — Tue, 23 Aug 2022 12:00:27 GMT-07:00

Current Challenges and Perspectives on Developing a Clinical Trial Design for ADPKD

Ostroff, Craig — Tue, 23 Aug 2022 11:21:43 GMT-07:00

Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion with CKD Progression

Ilori, Titilayo O. — Wed, 31 Aug 2022 10:49:50 GMT-07:00

The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography

Soomro, Qandeel H. — Thu, 25 Aug 2022 06:17:18 GMT-07:00

Rituximab in the Frail and Elderly with Severe ANCA-Associated GN

Brix, Silke R. — Tue, 02 Aug 2022 10:19:00 GMT-07:00

Perspectives on Drug Development in Early ADPKD

Mekahli, Djalila — Tue, 23 Aug 2022 11:45:42 GMT-07:00

Employment Status and Work Functioning among Kidney Transplant Recipients

Knobbe, Tim J. — Mon, 26 Sep 2022 06:49:55 GMT-07:00

Genome-Wide Epistatic Interaction between DEF1B and APOL1 High-Risk Genotypes for Chronic Kidney Disease

Vy, Ha My T. — Wed, 10 Aug 2022 06:32:06 GMT-07:00

Incorporating Training in POCUS in Nephrology Fellowship Curriculum

Reisinger, Nathaniel C. — Wed, 21 Sep 2022 10:43:19 GMT-07:00

Reducing Racial Disparities in Access to Transplant in the United States

Reed, Rhiannon D. — Mon, 19 Sep 2022 07:44:40 GMT-07:00

Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation

Ku, Elaine — Mon, 19 Sep 2022 06:10:48 GMT-07:00

Arterial Stiffness and Chronic Kidney Disease Progression in Children

Azukaitis, Karolis — Thu, 25 Aug 2022 06:17:18 GMT-07:00

Postoperative Acute Kidney Injury

Boyer, Naomi — Thu, 16 Jun 2022 09:33:17 GMT-07:00

Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.

Palliative Care for Hemodialysis Patients?

Brennan, Frank — Wed, 14 Sep 2022 07:07:42 GMT-07:00

Dialysis, Transplantation, and Work

Fadem, Stephen Z. — Mon, 26 Sep 2022 07:07:11 GMT-07:00

Oversimplification and Misplaced Blame will Not Solve the Complex Kidney Underutilization Problem

gaurav.gupta@vcuhealth.org — Wed, 05 Oct 2022 09:24:11 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

Genetic Variants of the COL4A3, COL4A4, and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients

Yuan, Xiaohan — Wed, 21 Sep 2022 09:47:36 GMT-07:00

Automated Kidney and Liver Segmentation in MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease: A Multicenter Study

roman-ulrich.mueller@uk-koeln.de — Wed, 05 Oct 2022 05:56:19 GMT-07:00

Background: Imaging-based total kidney and liver volumes (TKV, TLV) are major prognostic factors in autosomal dominant polycystic kidney disease (ADPKD) and endpoints for clinical trials. However, volumetry is time-consuming and reader-dependent in clinical practice. Our aim was to develop a fully automated method for joint kidney and liver segmentation in magnetic resonance imaging (MRI) and to evaluate its performance in a multi-sequence, multicenter setting. Methods: Convolutional neural network was trained on a large multicenter dataset consisting of 992 MRI scans of 327 patients. Manual segmentation delivered ground-truth labels. The model's performance was evaluated in a separate test dataset of 93 patients (350 MRI scans), as well as a heterogeneous external dataset of 831 MRI scans from 323 patients. Results: The segmentation model yielded excellent performance, achieving a median per-study Dice coefficient of 0.92-0.97 for the kidneys and 0.96 for the liver. Automatically computed TKV correlated highly with manual measurements (intraclass correlation coefficient (ICC): 0.996-0.999) with low bias and high precision (-0.2%±4.3% for axial and 0.5%±3.5% for coronal images). TLV estimation showed an ICC of 0.999 and bias/precision of -0.5%±3.3%. For the external dataset, the automated TKV demonstrated bias and precision of -1.3±7.4%. Conclusions: Our deep learning model enabled accurate segmentation of kidneys and liver and objective assessment of TKV and TLV. Importantly, this approach was validated with axial and coronal MRI scans from 40 different scanners, making implementation in clinical routine care feasible.

Belatacept-based Maintenance Immunosuppression Controls the Post-transplant Humoral Immune Response in Highly Sensitized Non-human primates

jean.kwun@duke.edu — Tue, 04 Oct 2022 01:24:08 GMT-07:00

Pre-existing donor-specific antibody (DSA) to major histocompatibility complex (MHC) antigens increases the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pre-transplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our pre-clinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific antithymocyte globulin (rhATG, n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post kidney transplantation was significantly reduced compared to maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsies showed a decrease in germinal center activity with low frequencies of T follicular helper cells as well as class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus (CMV) and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of anti-viral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients

Peter.Heeger@cshs.org — Tue, 04 Oct 2022 11:08:38 GMT-07:00

Background: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates tumor necrosis factor alpha (TNF) production that amplifies allograft inflammation and may negatively impact transplant outcomes. Methods: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase II clinical trial. Two-hundred twenty-five primary transplant recipients of deceased-donor kidneys (KTx) (38.2% Black/African-American, 44% White) were randomized to receive i.v. infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated prior to \ kidney reperfusion. All subjects received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary endpoint was the difference between groups in mean 24-month estimated glomerular filtration rate (eGFR). Results: There was no difference in the primary endpoint, 24-mo eGFR between IFX (52.45 ml/min/1.73m2, 95% CI 48.38-56.52) vs. PLBO (57.35 ml/min/1.73m2, 95% CI 53.18-61.52, p=0.099). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ and day 7 post-KTx plasma analyses showed ~10-fold lower TNF (p<0.001) in IFX vs. PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) vs. PLBO (13.4% p=0.004) with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) vs. PLBO (4.9%, p=0.06). Conclusions: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peri-transplant inflammation as a strategy to improve KTx outcomes.

The Case for Prioritizing Diversity in the Transplantation Workforce to Advance Kidney Health Equity

Butler, Thomas — Tue, 02 Aug 2022 12:56:00 GMT-07:00

Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study

Swartling, Oskar — Fri, 29 Jul 2022 10:32:22 GMT-07:00

Description and Outcomes of an Innovative Concurrent Hospice-Dialysis Program

Ernecoff, Natalie C. — Tue, 12 Jul 2022 11:22:38 GMT-07:00

Blocking CCL8-CCR8–Mediated Early Allograft Inflammation Improves Kidney Transplant Function

Dangi, Anil — Tue, 16 Aug 2022 07:40:22 GMT-07:00

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats

Bergling, Karin — Fri, 19 Aug 2022 10:51:52 GMT-07:00

Expression of Concern: Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy

American Society of Nephrology — Fri, 09 Sep 2022 08:51:00 GMT-07:00

Authors’ Reply: Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!

Segelmark, Mårten — Wed, 10 Aug 2022 10:14:36 GMT-07:00

Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies

Denic, Aleksandar — Wed, 03 Aug 2022 09:40:33 GMT-07:00

Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy

Reinhard, Linda — Fri, 19 Aug 2022 10:51:51 GMT-07:00

Dapagliflozin Prevents Kidney Glycogen Accumulation and Improves Renal Proximal Tubule Cell Functions in a Mouse Model of Glycogen Storage Disease Type 1b

D’Acierno, Mariavittoria — Tue, 12 Jul 2022 11:22:38 GMT-07:00

Ensuring Equitable Access to Dialysis: The Medicare Secondary Payer Act in Marietta Memorial Hospital Employee Health Benefit Plan v. DaVita, Inc.

Maliha, George — Wed, 03 Aug 2022 09:40:32 GMT-07:00

Policy and Kidney Community Engagement to Advance toward Greener Kidney Care

Struthers, Sarah A. — Thu, 18 Aug 2022 07:51:16 GMT-07:00

Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD

Binder, Veronika — Mon, 29 Aug 2022 01:48:09 GMT-07:00

Concurrent Hospice and Dialysis: Proof of Concept

Butler, Catherine R. — Mon, 12 Sep 2022 07:24:16 GMT-07:00

Sex Disparities in the Quality of Care for CKD

Reaves, Allison C. — Mon, 12 Sep 2022 07:24:16 GMT-07:00

Assessing Tubular Function, an Ignored Component of CKD, Might Be a Difference Maker!

Kalantari, Kambiz — Fri, 09 Sep 2022 08:51:00 GMT-07:00

This Month's Highlights

American Society of Nephrology — Mon, 12 Sep 2022 07:24:17 GMT-07:00

The Sweet Science of Glucose Transport

Sridhar, Vikas S. — Fri, 09 Sep 2022 08:51:00 GMT-07:00

Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!

Borza, Dorin-Bogdan — Wed, 10 Aug 2022 10:14:36 GMT-07:00

Authors’ Reply: Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial Dysfunction

Zafrani, Lara — Wed, 03 Aug 2022 10:38:18 GMT-07:00

Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial Dysfunction

Yang, Tinghang — Wed, 03 Aug 2022 10:08:29 GMT-07:00

SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses

Montez-Rath, Maria E. — Tue, 16 Aug 2022 07:40:22 GMT-07:00

Sex Differences in Age-Related Loss of Kidney Function

Melsom, Toralf — Wed, 17 Aug 2022 07:50:35 GMT-07:00

Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD

Bullen, Alexander L. — Tue, 16 Aug 2022 07:40:22 GMT-07:00

Acknowledging Socioecological Systems to Address the Systemic Racial Disparities in Children with Kidney Disease

Dawson, Anne E. — Wed, 29 Jun 2022 08:14:49 GMT-07:00

Renal Macrophages and Multinucleated Giant Cells: Ferrymen of the River Styx?

Sivaguru, Mayandi — Fri, 22 Jul 2022 01:35:59 GMT-07:00

The Integration of Diabetic Eye Screening into Hemodialysis Units in Northern Ireland

Cushley, Laura N. — Wed, 18 May 2022 01:30:25 GMT-07:00

Critical Role of Osteopontin in Maintaining Urinary Phosphate Solubility in CKD

Stubbs, Jason R. — Thu, 23 Jun 2022 06:48:58 GMT-07:00

Continuous Long-Term Physical Activity Monitoring in Hemodialysis Patients

Cohen, Brandon — Wed, 13 Jul 2022 11:26:13 GMT-07:00

Protein Restriction for CKD: Time to Move On

Obeid, Waseem — Thu, 23 Jun 2022 06:48:58 GMT-07:00

Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD

Pergola, Pablo E. — Wed, 29 Jun 2022 02:43:44 GMT-07:00

Osteopontin Regulates Phosphate Solubility to Prevent Mineral Aggregates in CKD

Imig, John D. — Thu, 29 Sep 2022 07:30:28 GMT-07:00

Dyspnea and Weight Loss following Left Internal Jugular Vein Dialysis Catheter Placement

Mhlana, Nontembiso — Thu, 29 Sep 2022 07:30:28 GMT-07:00

A Practical Guide to Genetic Testing for Kidney Disorders of Unknown Etiology

Aron, Abraham W. — Fri, 08 Jul 2022 01:22:03 GMT-07:00

Genetic testing is increasingly used in the workup and diagnosis of kidney disease and kidney-related disorders of undetermined cause. Out-of-pocket costs for clinical genetic testing have become affordable, and logistical hurdles overcome. The interest in genetic testing may stem from the need to make or confirm a diagnosis, guide management, or the patient’s desire to have a more informed explanation or prognosis. This poses a challenge for providers who do not have formal training in the selection, interpretation, and limitations of genetic tests. In this manuscript, we provide detailed discussion of relevant cases in which clinical genetic testing using a kidney gene panel was applied. The cases demonstrate identification of pathogenic variants for monogenic diseases—contrasting them from genetic risk alleles—and bring up diagnostic limitations and diagnostic utility of these tests in nephrology. This review aims to guide clinicians in formulating pretest conversations with their patients, interpreting genetic variant nomenclature, and considering follow-up investigations. Although providers are gaining experience, there is still risk of testing causing more anxiety than benefit. However, with provider education and support, clinical genetic testing applied to otherwise unexplained kidney-related disorders will increasingly serve as a valuable diagnostic tool with the potential to reshape how we consider and treat many kidney-related diagnoses.

A Post Hoc Analysis of KidneyIntelX and Cardiorenal Outcomes in Diabetic Kidney Disease

Nadkarni, Girish N. — Thu, 19 May 2022 08:54:56 GMT-07:00

FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease

Halim, Arvin — Tue, 05 Jul 2022 11:41:45 GMT-07:00

Global Dialysis Perspective: Sri Lanka

Wijewickrama, Eranga Sanjeewa — Fri, 08 Jul 2022 11:22:33 GMT-07:00

Development of an Administrative Data-Based Frailty Index for Older Adults Receiving Dialysis

Hall, Rasheeda K. — Tue, 19 Jul 2022 01:29:42 GMT-07:00

The Next Frontier: Biomarkers and Artificial Intelligence Predicting Cardiorenal Outcomes in Diabetic Kidney Disease

Braden, Gregory L. — Thu, 29 Sep 2022 07:30:28 GMT-07:00

Urinary Neutrophil Gelatinase–Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort Study

Katz-Greenberg, Goni — Wed, 13 Jul 2022 11:26:12 GMT-07:00

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy

Sanchez-Russo, Luis — Mon, 27 Jun 2022 12:01:40 GMT-07:00

Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

A Machine Learning Model for Predicting Mortality within 90 Days of Dialysis Initiation

Rankin, Summer — Wed, 20 Jul 2022 12:46:48 GMT-07:00

Development of New Equations Predicting the Mortality Risk of Patients on Continuous RRT

Kang, Min Woo — Tue, 02 Aug 2022 01:02:04 GMT-07:00

Global Dialysis Perspective: Nigeria

Okoye, Ogochukwu — Thu, 14 Jul 2022 10:34:18 GMT-07:00

Seeing the Light: Improving Diabetic Retinopathy Outcomes by Bringing Screening to the Dialysis Clinic

Klein, Klara R. — Thu, 29 Sep 2022 07:30:28 GMT-07:00

Exercising the FGF23-Cardiac Axis

Murray, Susan L. — Thu, 29 Sep 2022 07:30:28 GMT-07:00

White Plaques on the Tongue of a Patient with Advanced CKD

Gomes, Orlando Vieira — Thu, 29 Sep 2022 07:30:28 GMT-07:00

Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney Damage

Ertuglu, Lale A. — Mon, 27 Jun 2022 12:01:40 GMT-07:00

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage. Moreover, sodium accumulates nonosmotically in human tissue, including the skin and muscle, shifting the dogma on body sodium balance and its regulation. Emerging evidence suggests that high concentrations of extracellular sodium can directly trigger an inflammatory response in antigen-presenting cells (APCs), leading to hypertension and vascular and renal injury. Importantly, sodium entry into APCs is mediated by the epithelial sodium channel (ENaC). Although the role of the ENaC in renal regulation of sodium excretion and BP is well established, these new findings imply that the ENaC may also exert BP modulatory effects in extrarenal tissue through an immune-dependent pathway. In this review, we discuss the recent advances in our understanding of the pathophysiology of salt-sensitive hypertension with a particular focus on the roles of APCs and the extrarenal ENaC.

Post-Traumatic Stress Disorder and Post-Traumatic Growth following Kidney Transplantation

Nash, Rebekah P. — Mon, 01 Aug 2022 01:21:41 GMT-07:00

Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: COMMENTARY

Perazella, Mark A. — Wed, 26 Jan 2022 01:33:56 GMT-08:00

Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: PRO

Murphy, Mark E. — Wed, 26 Jan 2022 01:33:56 GMT-08:00

Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: CON

Mullaney, Scott R. — Wed, 26 Jan 2022 01:33:56 GMT-08:00

Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin Mistrafficking

Melissa.Little@mcri.edu.au — Tue, 27 Sep 2022 09:43:06 GMT-07:00

Background: NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in >1-month-old children. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was based on overexpression in some non-podocyte cell lines. Methods: We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2, encoding the protein changes p.G92C, p.P118L, p.R138Q, p.R168H and p.R291W, as well as control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p.R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated. Results: All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription. While wildtype PODOCIN localized to the membrane, distinct variant proteins displayed unique patterns of subcellular protein trafficking, some unreported. P118L and R138Q were preferentially retained in the endoplasmic reticulum (ER); R168H and R291W accumulated in the Golgi. Podocyte profiling demonstrated minimal diseaseassociated transcriptional change. All variants displayed podocyte-specific apoptosis, which was not linked to ER stress. NEPHRIN-PODOCIN co-localization elucidated the variantspecific impact on NEPHRIN association and hence NEPHRIN trafficking. Conclusion: Specific variants of endogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes. Understanding the impact of each variant on protein levels and localization and impact on NEPHRIN provides additional insight into the pathobiology of NPHS2 variants.

Induction of Long-lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients

christian.morath@med.uni-heidelberg.de — Thu, 22 Sep 2022 11:18:08 GMT-07:00

Background We recently demonstrated that donor-derived modified immune cells (MICs)—PBMCs that acquire immunosuppressive properties after a brief treatment— induced specific immunosuppression against the allogeneic donor when administered prior to kidney transplantation. We found an up to 68-fold increase in CD19+CD24hiCD38hi transitional B lymphocytes compared with transplanted controls. Methods Ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were followed to posttransplant day 1080. Results Patients treated with MICs had a favorable clinical course, showing no donor-specific HLA antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third-party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and 7-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively (P<0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets, and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiological role of regulatory B lymphocytes in donor-specific unresponsiveness. Conclusions These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population which, when administered to recipients prior to transplantation, may exert a beneficial effect on kidney transplants.

Continuous Glucose Monitoring to Optimize Management of Diabetes in Patients with Advanced CKD

Galindo, Rodolfo J. — Wed, 31 Aug 2022 10:49:50 GMT-07:00

Treatment of patients with diabetes and CKD includes optimizing glycemic control using lifestyle modifications and drugs that safely control glycemia and improve clinical kidney and cardiovascular disease outcomes. However, patients with advanced CKD, defined as eGFR <30 ml/min per 1.73 m2 or kidney disease treated with dialysis, have limitations to the use of some preferred glucose-lowering medications, are often treated with insulin, and experience high rates of severe hypoglycemia. Moreover, hemoglobin A1c accuracy decreases as GFR deteriorates. Hence, there is a need for better glycemic monitoring tools. Continuous glucose monitoring allows for 24-hour glycemic monitoring to understand patterns and the effects of lifestyle and medications. Real-time continuous glucose monitoring can be used to guide the administration of insulin and noninsulin therapies. Continuous glucose monitoring can overcome the limitations of self-monitored capillary glucose testing and hemoglobin A1c and has been shown to prevent hypoglycemic excursions in some populations. More data are needed to understand whether similar benefits can be obtained for patients with diabetes and advanced CKD. This review provides an updated approach to management of glycemia in advanced CKD, focusing on the role of continuous glucose monitoring in this high-risk population.

Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: COMMENTARY

rbrown@bidmc.harvard.edu — Tue, 20 Sep 2022 11:25:45 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the CON: 10.34067/KID.0002512022

Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: CON

awaron@stanford.edu — Tue, 20 Sep 2022 11:25:45 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the COMMENTARY: 10.34067/KID.0002502022

Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: PRO

kamelgharaibeh@gmail.com — Tue, 20 Sep 2022 11:25:45 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0002512022 and the COMMENTARY: 10.34067/KID.0002502022.

Metabolomic Profiling Identifies New Endogenous Markers of Tubular Secretory Clearance

mlgranda@uw.edu — Tue, 20 Sep 2022 07:33:25 GMT-07:00

BACKGROUND: The proximal tubules eliminate protein-bound toxins and drugs via secretion. Measurements or estimates of glomerular filtration rate do not necessarily reflect the physiologically distinct process of secretion. Clinical assessment of this important intrinsic kidney function requires endogenous markers that are highly specific for secretory transport. METHODS: We used metabolomics profiling to identify candidate markers of tubular secretory clearance in 50 participants from a kidney pharmacokinetics study. We measured metabolites in three sequential plasma samples and a concurrent 10-hour timed urine sample using hydrophilic interaction liquid chromatography-high resolution mass spectrometry. We quantified the association between estimated kidney clearance and normalized plasma peak height of each candidate solute to the clearance of administered furosemide, a protein-bound, avidly secreted medication. RESULTS: We identified 528 metabolites present in plasma and urine, excluding pharmaceuticals. We found 7 highly (>50%) protein bound and 49 poorly bound solutes with clearances significantly associated with furosemide clearance, and 18 solute clearances favoring an association with furosemide clearance by the 90th percentile when compared to GFR. We also found 4 highly bound and 42 poorly bound plasma levels that were significantly associated with furosemide clearance. CONCLUSIONS: We found several candidate metabolites whose kidney clearances or relative plasma levels are highly associated with furosemide clearance, an avidly secreted tracer medication of the organic anion transporters, highlighting their potential as endogenous markers of proximal tubular secretory clearance.

Acid-Base Disorders in the Critically Ill Patient

Achanti, Anand — Tue, 23 Aug 2022 07:06:40 GMT-07:00

Acid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non–gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non–gap acidoses result from disorders of renal tubular H+ transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO2 can be considered.

Indications for and Timing of Initiation of KRT

Ostermann, Marlies — Tue, 13 Sep 2022 05:36:59 GMT-07:00

KRT is considered for patients with severe AKI and associated complications. The exact indications for initiating KRT have been debated for decades. There is a general consensus that KRT should be considered in patients with AKI and medically refractory complications (“urgent indications”). “Relative indications” are more common but defined with less precision. In this review, we summarize the latest evidence from recent landmark clinical trials, discuss strategies to anticipate the need for KRT in individual patients, and propose an algorithm for decision making. We emphasize that the decision to consider KRT should be made in conjunction with other forms of organ support therapies and important nonkidney factors, including the patient’s preferences and overall goals of care. We also suggest future research to differentiate patients who benefit from timely initiation of KRT from those with imminent recovery of kidney function. Until then, efforts are needed to optimize the initiation and delivery of KRT in routine clinical practice, to minimize nonessential variation, and to ensure that patients with persistent AKI or progressive organ failure affected by AKI receive KRT in a timely manner.

Urinary sediment microscopy and correlations with kidney biopsy: red flags not to be missed

davidbnavarro@gmail.com — Mon, 12 Sep 2022 11:24:13 GMT-07:00

Background: Urinary sediment is a non-invasive laboratory test that can be performed by an automated analyzer, or manually by trained personnel. Manual examination remains the diagnostic standard because it excels at differentiating isomorphic from dysmorphic red blood cells, and identifying other urinary particles such as renal tubular epithelial cells (RTECs), lipids, crystals, and the composition of casts. This study aimed to investigate the prevalence of a complete profile of urinary sediment particles and its associations with histological lesions on kidney biopsy, regardless of diagnosis. Methods: Single center, observational retrospective study of 131 patients who had contemporary manual urinary sediment evaluation and kidney biopsy. A comprehensive set of urinary particles and histological lesions were quantified, and their associations were analyzed. Results: In our samples, we found an elevated frequency of findings suggestive of proliferative kidney disease, and a low frequency of particles evoking urological damage. The association of histological lesions and urinary particles was explored with a multivariate model. We identified urinary sediment characteristics that independently correlated with the presence of some histological lesions: urinary lipids with mesangial expansion [OR 2.86 (1.30-6.30)], mesangial hypercellularity [OR 2.44 (1.06-5.58)], and wire loops and/or hyaline deposits [OR 2.89 (1.13-7.73)], and urinary renal tubular epithelial cells with endocapillary hypercellularity [OR 3.17 (1.36-7.39)], neutrophils and/or karyorrhexis [OR 4.51 (1.61-12.61)], fibrinoid necrosis [OR 4.35 (1.48-12.74)], cellular/fibrocellular crescents [OR 5.27 (1.95-14.26)] and acute tubular necrosis [OR 2.31 (1.08-4.97)]. Conclusion: In a population of patients submitted to kidney biopsy, we found that the presence of some urinary particles (renal tubular epithelial cells, lipids, and dysmorphic erythrocytes), which are seldom reported by automated analyzers, is associated with active proliferative histological lesions. In this regard, manual urinary sediment evaluation may help to shape the indications for performing a kidney biopsy.

Global Perspectives in Acute Kidney Injury: Ecuador

dxjimenezmd@gmail.com — Thu, 08 Sep 2022 01:21:41 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it.

The Importance of Transplant Nephrology to a Successful Kidney Transplant Program

Moe, Sharon M. — Mon, 01 Aug 2022 06:15:53 GMT-07:00

Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United States

Singh, Neeraj — Mon, 01 Aug 2022 06:15:52 GMT-07:00

Extracellular Vesicles as Theranostic Tools in Kidney Disease

Huang, Weijun — Tue, 08 Mar 2022 09:14:49 GMT-08:00

Extracellular vesicles are important vectors for cell-cell communication and show potential value for diagnosis and treatment of kidney diseases. The pathologic diagnosis of kidney diseases relies on kidney biopsy, whereas collection of extracellular vesicles from urine or circulating blood may constitute a less invasive diagnostic tool. In particular, urinary extracellular vesicles released mainly from resident kidney cells might provide an alternative tool for detection of kidney injury. Because extracellular vesicles mirror many features of their parent cells, cargoes of several populations of urinary extracellular vesicles are promising biomarkers for disease processes, like diabetic kidney disease, kidney transplant, and lupus nephritis. Contrarily, extracellular vesicles derived from reparative cells, such as mesenchymal stem cells, tubular epithelial progenitor cells, and human umbilical cord blood represent promising regenerative tools for treatment of kidney diseases. Furthermore, induced pluripotent stem cells–derived and engineered extracellular vesicles are being developed for specific applications for the kidney. Nevertheless, some assumptions regarding the specificity and immunogenicity of extracellular vesicles remain to be established. This review focuses on the utility of extracellular vesicles as therapeutic and diagnostic (theranostic) tools in kidney diseases and future directions for studies.

Choosing the Right Treatment in Patients with Lupus Nephritis

Mejia Vilet, Juan Manuel — Fri, 29 Jul 2022 05:37:25 GMT-07:00

Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance

Barah, Masoud — Fri, 22 Jul 2022 08:54:11 GMT-07:00

Chronic Kidney Disease and Severe Mental Illness

Cogley, Clodagh — Thu, 31 Mar 2022 06:26:06 GMT-07:00

Individuals with severe mental illness, including conditions such as schizophrenia and bipolar disorder, are at a higher risk of developing CKD. Higher incidences of CKD in this population can be partially explained by known risk factors, such as the use of lithium treatment and higher rates of cardiovascular disease. However, this does not fully explain the higher proportion of CKD in individuals with severe mental illness, and further research investigating the factors influencing disease onset and progression is needed. Similarly, although it is well documented that mental health difficulties, such as depression and anxiety, are highly prevalent among individuals with CKD, there is a lack of published data regarding the rates of severe mental illness in individuals with CKD. Furthermore, for individuals with CKD, having severe mental illness is associated with poor health outcomes, including higher mortality rates and higher rates of hospitalizations. Evidence also suggests that individuals with severe mental illness receive suboptimal kidney care, have fewer appointments with nephrologists, and are less likely to receive a kidney transplant. Limited research suggests that care might be improved through educating kidney health care staff regarding the needs of patients with severe mental illness and by facilitating closer collaboration with psychiatry. Further research investigating the rates of severe mental illness in patients with CKD, as well as the barriers and facilitators to effective care for this population, is clearly required to inform the provision of appropriate supports and to improve health outcomes for individuals with CKD and co-occurring severe mental illness.

Music for Health

Nobakht, Niloofar — Wed, 15 Jun 2022 10:07:23 GMT-07:00

Patient Preferences for Waiting Time and Kidney Quality

Mehrotra, Sanjay — Fri, 19 Aug 2022 06:15:27 GMT-07:00

Acute Kidney Injury in Critically Ill Patients with Cancer

Gupta, Shruti — Fri, 25 Mar 2022 07:54:20 GMT-07:00

Advances in cancer therapy have significantly improved overall patient survival; however, AKI remains a common complication in patients with cancer, occurring in anywhere from 11% to 22% of patients, depending on patient-related or cancer-specific factors. Critically ill patients with cancer as well as patients with certain malignancies (e.g., leukemias, lymphomas, multiple myeloma, and renal cell carcinoma) are at highest risk of developing AKI. AKI may be a consequence of the underlying malignancy itself or from the wide array of therapies used to treat it. Cancer-associated AKI can affect virtually every compartment of the nephron and can present as subclinical AKI or as overt acute tubular injury, tubulointerstitial nephritis, or thrombotic microangiopathy, among others. AKI can have major repercussions for patients with cancer, potentially jeopardizing further eligibility for therapy and leading to greater morbidity and mortality. This review highlights the epidemiology of AKI in critically ill patients with cancer, risk factors for AKI, and common pathologies associated with certain cancer therapies, as well as the management of AKI in different clinical scenarios. It highlights gaps in our knowledge of AKI in patients with cancer, including the lack of validated biomarkers, as well as evidence-based therapies to prevent AKI and its deleterious consequences.

Existing Transplant Nephrology Compensation Models and Opportunities for Equitable Pay

Josephson, Michelle A. — Mon, 01 Aug 2022 06:15:52 GMT-07:00

Central Venous Catheter Malfunction in Children

Bruno, Claudia — Mon, 11 Jul 2022 05:42:06 GMT-07:00

Unraveling the Mysteries of CKD of Uncertain Etiology

Garcia, Pablo — Tue, 09 Aug 2022 05:56:25 GMT-07:00

Mitigating Pain in People Undergoing Hemodialysis

Davison, Sara N. — Wed, 24 Aug 2022 05:52:34 GMT-07:00

Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients

Coyne, Daniel W. — Tue, 02 Aug 2022 06:41:53 GMT-07:00

Getting a Kidney: Where Is Patient Choice?

Lennon, Michael “Jack” — Fri, 19 Aug 2022 07:58:24 GMT-07:00

Advancing Kidney Health Equity

Mohottige, Dinushika — Tue, 16 Aug 2022 07:40:06 GMT-07:00

Improving the Utilization of Deceased Donor Kidneys by Prioritizing Patient Preferences

Mohan, Sumit — Fri, 19 Aug 2022 07:58:25 GMT-07:00

Effect of Music in Reducing Pain during Hemodialysis Access Cannulation

Inayama, Emi — Wed, 24 Aug 2022 05:52:34 GMT-07:00

Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis

Melchinger, Hannah — Wed, 10 Aug 2022 06:32:06 GMT-07:00

Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images

Testa, Francesca — Tue, 26 Jul 2022 08:45:14 GMT-07:00

The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function

Krupka, Emily — Tue, 16 Aug 2022 07:40:06 GMT-07:00

Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology

Holliday, Michael W. — Tue, 09 Aug 2022 05:36:51 GMT-07:00

Transplant Nephrology

Chonchol, Michel — Mon, 01 Aug 2022 09:32:31 GMT-07:00

Incidence and Risk Factors for Dialysis Reinitiation among Patients with a History of Dialysis Dependency

elaine.ku@ucsf.edu — Thu, 11 Aug 2022 06:20:03 GMT-07:00

Meta-analysis and cohort study of histopathological and clinical outcomes in ANCA negative versus positive vasculitis

lauren.floyd@doctors.org.uk — Mon, 05 Sep 2022 07:01:22 GMT-07:00

Background: ANCA negative pauci-immune glomerulonephritis (PIGN) represents a rare and often under-studied subgroup of the vasculitidies. This study aims to investigate differences in the clinical phenotype, renal histological features and clinical outcomes amongst patients with PIGN, with and without serum ANCA positivity. Methods: A cohort of biopsy proven PIGN with and without detectable circulating ANCA was constructed from a single centre between 2006 and 2016. Primary outcomes compared clinical presentation and histopathological features according to ANCA status, with multivariate Cox regression to compare mortality and end-stage kidney disease (ESKD). A systematic review and meta-analysis of the published literature was undertaken. Results: In our cohort of 146 patients; 21.9% (n=32) had ANCA negative disease with a comparatively younger mean age at diagnosis; 51.4 vs 65.6 years (P<0.001). Fourteen studies, inclusive of our cohort were eligible for meta-analysis, totalling 301 ANCA negative patients. Those with ANCA negative disease tended to have fewer extra-renal symptoms and a higher frequency of renal limited disease, but both failed to reach statistical significance (P=0.92 and P=0.07). The risk of ESKD was significantly higher in seronegative disease (RR 2.28 [1.42-3.65], P<0.001), reflecting our experience, with a fivefold increased risk of ESKD in ANCA negative disease (P<0.001). No significant difference in the chronicity of histopathological findings was seen and the meta-analysis showed no difference in morality (RR 1.22 [0.63-2.38], P=0.55). Conclusion: Our findings demonstrate that ANCA negative PIGN presents in younger patients, with fewer extra renal manifestations and higher ESKD risk despite a lack of difference in histopathology. This study provides the impetus for further research into the pathogenesis, treatment response and duration of immunotherapy in ANCA negative disease. We suggest that the absence of positive ANCA serology should not discourage treatment and for clinical trials to include ANCA negative patients.

The Highs and Lows of Potassium Intake in CKD—Does One Size Fit All?

Terker, Andrew S. — Tue, 19 Jul 2022 11:52:25 GMT-07:00

The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status Quo

Conway, Paul T. — Tue, 02 Aug 2022 12:56:00 GMT-07:00

Emerging Insights into Glomerular Vascular Pole and Microcirculation

Goligorsky, Michael S. — Tue, 19 Jul 2022 11:52:26 GMT-07:00

The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1–induced mesangiolysis and intravital microscopy to unequivocally establish in vivo the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.

Nuclear Condensation of CDYL Links Histone Crotonylation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease

Dang, Lin — Tue, 02 Aug 2022 01:10:36 GMT-07:00

Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD Outcomes

Liu, Caroline — Wed, 20 Jul 2022 06:30:48 GMT-07:00

KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency–Related Polycystic Kidney Disease

Rah, Gyuyeong — Fri, 12 Aug 2022 12:00:51 GMT-07:00

Sources of Variation in the Carbon Footprint of Hemodialysis Treatment

Sehgal, Ashwini R. — Thu, 02 Jun 2022 10:56:36 GMT-07:00

Hurricanes and Mortality among Patients Receiving Dialysis

Blum, Matthew F. — Thu, 14 Jul 2022 05:49:43 GMT-07:00

Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria

Shin, Jung-Im — Tue, 19 Jul 2022 10:23:57 GMT-07:00

Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy

Gao, Shuang — Fri, 01 Jul 2022 06:03:14 GMT-07:00

The Potential for Pragmatic Trials to Reduce Racial and Ethnic Disparities in Kidney Disease

Dember, Laura M. — Wed, 03 Aug 2022 09:40:32 GMT-07:00

Health Care Equity and Justice Scorecard To Increase Diversity in Clinical Trial Recruitment and Retention

Nicholas, Susanne B. — Wed, 29 Jun 2022 08:14:50 GMT-07:00

Assessing the Carbon Footprint of Hemodialysis: A First Step Toward Environmentally Sustainable Kidney Care

Barraclough, Katherine A. — Fri, 15 Jul 2022 06:33:18 GMT-07:00

Decorating Histones in Polycystic Kidney Disease

Ramalingam, Harini — Tue, 02 Aug 2022 01:10:35 GMT-07:00

Searching for the Risk-Benefit Profile of Higher Potassium Intake in CKD: Primum Non Nocere

Guedes, Murilo — Thu, 04 Aug 2022 08:12:47 GMT-07:00

Complement is Complimentary in Membranous Nephropathy

Kettritz, Ralph — Wed, 13 Jul 2022 06:34:38 GMT-07:00

This Month's Highlights

American Society of Nephrology — Wed, 31 Aug 2022 10:00:23 GMT-07:00

Authors’ Reply: “The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status Quo” and “The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do Better”

Quinn, Robert R. — Tue, 02 Aug 2022 12:56:01 GMT-07:00

The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do Better

Mendu, Mallika L. — Tue, 02 Aug 2022 12:56:00 GMT-07:00

Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Gritter, Martin — Tue, 24 May 2022 11:35:29 GMT-07:00

Cation Channel Activity of Apolipoprotein L1 is Modulated by Haplotype Background

Winkler, Rebecca L. — Fri, 15 Jul 2022 06:33:19 GMT-07:00

Kidney Failure Alters Parathyroid Pin1 Phosphorylation and Parathyroid Hormone mRNA-Binding Proteins, Leading to Secondary Hyperparathyroidism

Hassan, Alia — Fri, 12 Aug 2022 12:00:52 GMT-07:00

Transcription Factors YAP/TAZ and SRF Cooperate To Specify Renal Myofibroblasts in the Developing Mouse Kidney

Drake, Keri A. — Tue, 02 Aug 2022 12:20:32 GMT-07:00

Prolonged Intermittent Kidney Replacement Therapy

Levine, Zoey — Mon, 29 Aug 2022 06:04:11 GMT-07:00

Kidney replacement therapy (KRT) is a vital, supportive treatment for patients with critical illness and severe AKI. The optimal timing, dose, and modality of KRT have been studied extensively, but gaps in knowledge remain. With respect to modalities, continuous KRT and intermittent hemodialysis are well-established options, but prolonged intermittent KRT is becoming more prevalent worldwide, particularly in emerging countries. Compared with continuous KRT, prolonged intermittent KRT offers similar hemodynamic stability and overall cost savings, and its intermittent nature allows patients time off therapy for mobilization and procedures. When compared with intermittent hemodialysis, prolonged intermittent KRT offers more hemodynamic stability, particularly in patients who remain highly vulnerable to hypotension from aggressive ultrafiltration over a shorter duration of treatment. The prescription of prolonged intermittent KRT can be tailored to patients’ progression in their recovery from critical illness, and the frequency, flow rates, and duration of treatment can be modified to avert hemodynamic instability during de-escalation of care. Dosing of prolonged intermittent KRT can be extrapolated from urea kinetics used to calculate clearance for continuous KRT and intermittent hemodialysis. Practice variations across institutions with respect to terminology, prescription, and dosing of prolonged intermittent KRT create significant challenges, especially in creating specific drug dosing recommendations during prolonged intermittent KRT. During the coronavirus disease 2019 pandemic, prolonged intermittent KRT was rapidly implemented to meet the KRT demands during patient surges in some of the medical centers overwhelmed by sheer volume of patients with AKI. Ideally, implementation of prolonged intermittent KRT at any institution should be conducted in a timely manner, with judicious planning and collaboration among nephrology, critical care, dialysis and intensive care nursing, and pharmacy leadership. Future analyses and clinical trials with respect to prescription and delivery of prolonged intermittent KRT and clinical outcomes will help to guide standardization of practice.

Endothelial KLF11 as a Nephroprotectant in AKI

Ghajar-Rahimi, Gelare — Thu, 25 Aug 2022 06:30:29 GMT-07:00

Guiding Kidney Transplantation Candidates for Effective Weight Loss: A Clinical Cohort Study

Kukla, Aleksandra — Mon, 16 May 2022 01:21:46 GMT-07:00

High Ultrafiltration Rates and Mortality in Hemodialysis Patients: Current Evidence and Future Steps

Ravi, Katherine Scovner — Thu, 25 Aug 2022 06:30:29 GMT-07:00

Intensive RRT for AKI: Dial Down Your Enthusiasm!

Clark, Edward G. — Fri, 03 Jun 2022 03:49:41 GMT-07:00

County-Level Dialysis Facility Supply and Distance Traveled to Facilities among Incident Kidney Failure Patients

Velázquez, Alexis F. — Tue, 24 May 2022 01:38:02 GMT-07:00

Proportion of Hemodialysis Treatments with High Ultrafiltration Rate and the Association with Mortality

Navarrete, José E. — Thu, 05 May 2022 01:22:35 GMT-07:00

Fundamentals of Arterial Blood Gas Interpretation

Yee, Jerry — Fri, 03 Jun 2022 01:46:37 GMT-07:00

Acid-base disturbances in patients with cardiopulmonary or other disorders are common and are often misinterpreted or interpreted incompletely. Treating acid-base disorders in greater detail facilitates pathophysiologic understanding and improved therapeutic planning. Understanding the ratiometric relationship between the lungs, which excrete volatile acid as carbon dioxide, and the kidneys, which contribute to maintenance of plasma bicarbonate, allows precise identification of the dominant acid-base disturbance when more than a simple disorder is present and aids in executing a measured treatment response. Concordantly, mapping paired values of the partial pressure of carbon dioxide (PCO2) and the bicarbonate concentration ([HCO3–]) on a Cartesian coordinate system visually defines an acid-base disorder and validates the ratiometric methodology. We review and demonstrate the algebraic and logarithmic methods of arterial blood gas analysis through the example of a complex acid-base disorder, emphasizing examination of the PCO2-to-[HCO3–] ratio.

Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal Lipotoxicity

Byun, Jae Hyun — Wed, 27 Apr 2022 11:32:08 GMT-07:00

Global Perspectives in Acute Kidney Injury: England

Lewington, Andrew — Wed, 29 Jun 2022 04:04:15 GMT-07:00

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19

Kanduri, Swetha R. — Wed, 18 May 2022 01:30:25 GMT-07:00

Global Dialysis Perspective: Ethiopia

Mengistu, Yewondwossen T. — Tue, 24 May 2022 01:38:03 GMT-07:00

Persistent Abdominal Pain following Peritoneal Dialysis Catheter Removal for Peritonitis

Khan, Sana F. — Thu, 25 Aug 2022 06:30:29 GMT-07:00

Design and Basic Characteristics of a National Patient-Powered Registry in ADPKD

Hoover, Elise — Fri, 20 May 2022 02:09:38 GMT-07:00

The Many Lives of PCSK9: Therapeutic Implications

Pressly, Jeffrey — Thu, 25 Aug 2022 06:30:29 GMT-07:00

KLF11 Is a Novel Endogenous Protectant against Renal Ischemia-Reperfusion Injury

Nath, Karl A. — Fri, 06 May 2022 01:23:10 GMT-07:00

Hypercalcemia and Suppressed Intact PTH in a Hemodialysis Patient

Donato, Beatriz — Thu, 25 Aug 2022 06:30:29 GMT-07:00

Bariatric Surgery Decreases Barriers for Kidney Transplant: Are There Other Weight-Loss Options?

Lorden, Heather M. — Thu, 25 Aug 2022 06:30:29 GMT-07:00

Polycystic Ovary Syndrome: Insights from Preclinical Research

Reckelhoff, Jane F. — Fri, 17 Jun 2022 01:26:06 GMT-07:00

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and polycystic ovaries. The most common type (80%) of PCOS includes hyperandrogenemia. PCOS is also characterized by obesity or overweight (in 80% of US women with PCOS), insulin resistance with elevated plasma insulin but not necessarily hyperglycemia, dyslipidemia, proteinuria, and elevated BP. Although elevated compared with age-matched controls, BP may not reach levels considered treatable according to the current clinical hypertension guidelines. However, it is well known that elevated BP, even modestly so, increases the risk of cardiovascular disease. We have developed a model of hyperandrogenemia in rodents that mimics the characteristics of PCOS in women, with increases in body weight, insulin resistance, dyslipidemia, andproteinuria and elevated BP. This review discusses potential mechanisms responsible for the elevated BP in the adult and aging PCOS rat model that may be extrapolated to women with PCOS.

Fostering Scientific Innovation to Impact AKI: A Roadmap from ASN’s AKINow Basic Science Workgroup

Parikh, Samir M. — Fri, 17 Jun 2022 03:54:12 GMT-07:00

Associations of Anxiety during the COVID-19 Pandemic with Patient Characteristics and Behaviors in CKD Patients: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Dorans, Kirsten S. — Wed, 25 May 2022 06:56:49 GMT-07:00

Are Undergraduates Familiar with Nephrology as a Medical Specialty? A Single Site Survey of Undergraduate Students

Hopkins, Julia — Thu, 02 Jun 2022 01:28:26 GMT-07:00

Balancing Hyperkalemia Risks with Clinical Benefits of Renin-Angiotensin-Aldosterone Inhibitors/Mineralocorticoid Receptor Antagonists Blockade: It’s Apples and Oranges

Leon, Silvia J. — Wed, 18 May 2022 11:34:09 GMT-07:00

Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving Dialysis

Jain, Nishank — Wed, 18 May 2022 09:36:27 GMT-07:00

Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: PRO

andrew.donati@yale.edu — Thu, 20 Jan 2022 12:28:46 GMT-08:00

Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: CON

Gallagher, Martin P. — Thu, 20 Jan 2022 12:28:46 GMT-08:00

Should Corticosteroids be Used To Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: COMMENTARY

Praga, Manuel — Thu, 20 Jan 2022 12:28:46 GMT-08:00

Learning Methodological Lessons from Exemplar Studies in Nephrology: PEXIVAS and Sample Size Calculation

Sandys, Vicki — Fri, 20 May 2022 11:12:10 GMT-07:00

Associations of Dysnatremia with COVID-19 Status and Mortality

Liu, Diane — Fri, 03 Jun 2022 03:49:41 GMT-07:00

Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis

Nagano, China — Tue, 24 May 2022 01:38:02 GMT-07:00

The Utilization of Packed Red Blood Cell Transfusion and Angiography in Pediatric Inpatients after Kidney Biopsy in the United States

Afolabi, Halimat — Wed, 18 May 2022 09:36:27 GMT-07:00

Continuous KRT

Teixeira, J. Pedro — Thu, 18 Aug 2022 10:25:48 GMT-07:00

AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.

How I Manage Hypertension and Proteinuria Associated with VEGF Inhibitor

Rashidi, Arash — Wed, 17 Aug 2022 06:47:39 GMT-07:00

Soluble ACE2 is Filtered into the Urine

gurley@ohsu.edu — Wed, 10 Aug 2022 01:41:42 GMT-07:00

Background: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, ACE2 has highest levels of abundance in the kidney with expression in a number of extra-renal tissues as well. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2 knockout mice. Methods: To examine the impact of ACE2 expressed in the kidney, relative to extra-renal expression, on the development of hypertension, we utilized a kidney cross-transplantation strategy with ACE2 KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney such that 4 experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we utilized nano-scale mass spectrometry-based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. Result: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice which lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII hypertension suggests that sACE2 originating from extra-renal tissues is able to reach the kidney and can be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nano-scale proteomics to detect peptides derived from ACE2 in Bowman's space. Conclusions: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular flitration barrier.

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Wang, Shudan — Tue, 26 Jul 2022 10:31:25 GMT-07:00

Trainee Perspectives on Race, Antiracism, and the Path toward Justice in Kidney Care

Heffron, Anna S. — Tue, 07 Jun 2022 07:32:08 GMT-07:00

Age and the Course of GFR in Persons Aged 70 and Above

Schaeffner, Elke S. — Mon, 18 Jul 2022 11:41:05 GMT-07:00

HIF-PHIs for Anemia Management in CKD

McCallum, Wendy — Tue, 05 Jul 2022 05:42:16 GMT-07:00

Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and Mortality

Ohkuma, Toshiaki — Wed, 27 Jul 2022 05:41:45 GMT-07:00

Correction: CRRT Fluid Choices: A Solution for a Common Problem?

American Society of Nephrology — Mon, 25 Jul 2022 06:11:43 GMT-07:00

Correction: Fractional Excretion of Sodium (FENa): An Imperfect Tool for a Flawed Question

American Society of Nephrology — Mon, 25 Jul 2022 06:11:43 GMT-07:00

Anxiety, Comorbid Depression, and Dialysis Symptom Burden

Cukor, Daniel — Mon, 13 Jun 2022 05:05:30 GMT-07:00

Physiology of the Aging Kidney

Delanaye, Pierre — Mon, 18 Jul 2022 11:55:37 GMT-07:00

Health Care for Older Adults with Kidney Failure

Fonseca-Correa, Jorge I. — Thu, 28 Jul 2022 07:07:40 GMT-07:00

How I Treat IgA Nephropathy

Reich, Heather N. — Wed, 08 Jun 2022 05:51:14 GMT-07:00

Calamari, Hyperkalemia, and Renin-Angiotensin System Blockade

Janak, Emily — Wed, 27 Jul 2022 06:06:27 GMT-07:00

Novel Approaches for the Removal of Uremic Solutes

Tang, Mengyao — Thu, 14 Jul 2022 07:20:22 GMT-07:00

Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD

Hiremath, Swapnil — Thu, 09 Jun 2022 09:42:01 GMT-07:00

Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis Patients

Krediet, Raymond T. — Tue, 15 Feb 2022 07:19:38 GMT-08:00

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.

Removal of Uremic Solutes from Dialysate by Activated Carbon

Lee, Seolhyun — Thu, 14 Jul 2022 07:20:22 GMT-07:00

Association of HLA Mismatches and Histology Suggestive of Antibody-Mediated Injury in the Absence of Donor-Specific Anti-HLA Antibodies

Senev, Aleksandar — Wed, 01 Jun 2022 11:56:25 GMT-07:00

Long-Term Effect of Physical Exercise on the Risk for Hospitalization and Death in Dialysis Patients

Mallamaci, Francesca — Mon, 25 Jul 2022 05:57:33 GMT-07:00

Quality of Life before and after the Start of Dialysis in Older Patients

de Rooij, Esther N.M. — Thu, 28 Jul 2022 06:55:05 GMT-07:00

Drug-Induced Acute Kidney Injury

Perazella, Mark A. — Thu, 10 Mar 2022 07:00:02 GMT-08:00

Medications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell–mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.

Radiographic Contrast Media and the Kidney

Cashion, Winn — Fri, 01 Jul 2022 06:35:28 GMT-07:00

AKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature

Hingorani, Sangeeta — Tue, 19 Jul 2022 10:29:53 GMT-07:00

Patterns in Tacrolimus Variability and Association with De Novo Donor-Specific Antibody Formation in Pediatric Kidney Transplant Recipients

Piburn, Kim H. — Tue, 26 Jul 2022 08:45:14 GMT-07:00

Pathophysiological Implications of Variability in Blood Tacrolimus Levels in Pediatric and Adolescent Kidney Transplant Recipients

Becker-Cohen, Rachel — Tue, 26 Jul 2022 08:45:14 GMT-07:00

Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart Failure

Akwo, Elvis — Thu, 28 Jul 2022 06:55:05 GMT-07:00

Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized Trials

haller.hermann@mh-hannover.de — Tue, 02 Aug 2022 01:21:50 GMT-07:00

Background: Hyperkalemia is a common electrolyte abnormality in patients with chronic kidney disease (CKD), which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This post hoc subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with non-dialysis CKD. Methods: Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined. Patients had baseline diagnosis of CKD, hyperkalemia (serum potassium >5.0 mEq/L) and received patiromer 8.4-33.6 g/day. Patients were stratified by baseline estimated glomerular filtration rate (eGFR) into two subgroups: severe/end-stage CKD (Stage 3b-5; eGFR<45 mL/min/1.73m2) and mild/moderate CKD (Stage 1-3a; eGFR ≥45 mL/min/1.73m2). Efficacy was assessed by the change in serum potassium (mean±standard error [SE]) from baseline to week 4. Safety assessments included incidence and severity of adverse events (AEs). Results: Efficacy analyses (N=626; 62% male, mean age 66 years) included 417 (67%) patients with severe/end-stage CKD and 209 (33%) with mild/moderate CKD. Most patients were receiving RAASi therapy at baseline (severe/end-stage CKD: 92%; mild/moderate CKD: 98%). The mean±SE change in serum potassium (baseline to week 4) was −0.84±0.03 in the severe/end-stage CKD subgroup, and −0.60±0.04 mEq/L in the mild/moderate CKD subgroup. AEs were reported for 40% and 27% patients in the severe/end-stage and mild/moderate CKD subgroups, respectively, with 16% and 12% reporting AEs considered related to patiromer. The most frequent AEs were mild-to-moderate constipation (8% and 3%) and diarrhea (4% and 2%). AEs leading to patiromer discontinuation occurred in 6% and 2% of patients with severe/end-stage CKD, and mild/moderate CKD, respectively. Conclusions: Patiromer was effective for treatment of hyperkalemia and well tolerated in patients across stages of CKD, most of whom were receiving guideline-recommended RAASi therapy.

Targeted Disruption of a Proximal Tubule–Specific TMEM174 Gene in Mice Causes Hyperphosphatemia and Vascular Calcification

Miyazaki-Anzai, Shinobu — Fri, 22 Apr 2022 10:52:49 GMT-07:00

A Composite End Point of Graft Status and eGFR at 1 Year to Improve the Scientific Registry of Transplant Recipients’ Five-Tier Rating System

Wang, Kaicheng — Tue, 10 May 2022 08:57:24 GMT-07:00

High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity

Ulmer, Candice Z. — Fri, 08 Apr 2022 08:35:43 GMT-07:00

Full-length parathyroid hormone (PTH 1–84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1–84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1–84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1–84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1–84, PTH fragments, and post-translationally modified PTH 1–84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.

The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis

Richerson, Wesley T. — Fri, 01 Jul 2022 06:03:12 GMT-07:00

Optimizing the Design and Analysis of Future AKI Trials

Legrand, Matthieu — Wed, 13 Jul 2022 06:34:39 GMT-07:00

AKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment. This article, derived from the “AKI” session of the “Kidney Disease Clinical Trialists” virtual workshop held in October 2021, reviews barriers to and strategies for improving the design and implementation of clinical trials in patients with, or at risk of, developing AKI. The novel approaches to trial design included in this review span adaptive trial designs that increase the knowledge gained from each trial participant; pragmatic trial designs that allow for the efficient enrollment of sufficiently large numbers of patients to detect small, but clinically significant, treatment effects; and platform trial designs that use one trial infrastructure to answer multiple clinical questions simultaneously. This review also covers novel approaches to clinical trial analysis, such as Bayesian analysis and assessing heterogeneity in the response to therapies among trial participants. We also propose a road map and actionable recommendations to facilitate the adoption of the reviewed approaches. We hope that the resulting road map will help guide future clinical trial planning, maximize learning from AKI trials, and reduce the risk of missing important signals of benefit (or harm) from trial interventions.

Channel Function of Polycystin-2 in the Endoplasmic Reticulum Protects against Autosomal Dominant Polycystic Kidney Disease

Padhy, Biswajit — Thu, 14 Jul 2022 05:49:42 GMT-07:00

Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity

Chen, Dhruti P. — Tue, 07 Jun 2022 08:48:24 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 29 Jul 2022 10:00:25 GMT-07:00

On the Importance of Considering Glycosylation When Evaluating Biologic Therapies

Lemaire, Mathieu — Fri, 15 Jul 2022 06:33:19 GMT-07:00

Serum Protein-Induced Tubular Injury

O’Neill, W. Charles — Fri, 29 Jul 2022 10:00:25 GMT-07:00

Collaboration between Dialysis Providers

Silberzweig, Jeffrey — Thu, 02 Jun 2022 10:56:36 GMT-07:00

A Deep Learning Approach for Automated Segmentation of Kidneys and Exophytic Cysts in Individuals with Autosomal Dominant Polycystic Kidney Disease

Kim, Youngwoo — Wed, 29 Jun 2022 08:14:50 GMT-07:00

Vaccination, Transplantation, and a Social Contract

Kates, Olivia S. — Wed, 11 May 2022 08:24:36 GMT-07:00

Complementary Nck1/2 Signaling in Podocytes Controls α Actinin-4–Mediated Actin Organization, Adhesion, and Basement Membrane Composition

Martin, Claire E. — Fri, 29 Jul 2022 10:00:25 GMT-07:00

Housing: A Critical Contributor to Kidney Disease Disparities

Novick, Tessa K. — Wed, 11 May 2022 08:24:36 GMT-07:00

Myeloid CCR2 Promotes Atherosclerosis after AKI

Hüsing, Anne M. — Tue, 10 May 2022 08:57:25 GMT-07:00

Unfulfilled Expectations Open New Horizons: What Have We Learned about Volume-Regulated Anion Channels in the Kidney?

Pochynyuk, Oleh — Fri, 15 Jul 2022 06:33:18 GMT-07:00

Authors’ Reply: Serum Protein-induced Tubular Injury

Lidberg, Kevin — Fri, 29 Jul 2022 10:00:25 GMT-07:00

Polycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium

Caplan, Michael J. — Fri, 29 Jul 2022 10:00:25 GMT-07:00

Coronary Artery Calcification Score and the Progression of Chronic Kidney Disease

Yun, Hae-Ryong — Thu, 02 Jun 2022 10:56:36 GMT-07:00

Renal Deletion of LRRC8/VRAC Channels Induces Proximal Tubulopathy

López-Cayuqueo, Karen I. — Fri, 01 Jul 2022 06:03:13 GMT-07:00

Addressing Inequities in Kidney Care for Indigenous People in Canada

Harasemiw, Oksana — Mon, 06 Jun 2022 08:07:49 GMT-07:00

Identifying Antigen-Specific T Cells in ANCA-Associated Vasculitis: A Glimpse of the Future?

Shochet, Lani — Fri, 29 Jul 2022 10:00:25 GMT-07:00

Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial

Provenzano, Michele — Tue, 19 Apr 2022 09:24:58 GMT-07:00

Authors’ Reply: “On the Importance of Considering Glycosylation when Evaluating Biologic Therapies”

Angeletti, Andrea — Fri, 15 Jul 2022 06:33:19 GMT-07:00

Development of a Patient Preference Survey for Wearable Kidney Replacement Therapy Devices

Flythe, Jennifer E. — Fri, 06 May 2022 11:37:58 GMT-07:00

Do Proton-Pump Inhibitors Cause CKD and Progression of CKD?: PRO

Awdishu, Linda — Tue, 04 Jan 2022 05:02:17 GMT-08:00

Global Dialysis Perspective: Nepal

Sharma, Ishwor — Wed, 27 Apr 2022 09:28:29 GMT-07:00

Not So Fast: Kidney Replacement Therapy for Critically Ill Patients with AKI

Sanghavi, Sarah F. — Wed, 11 May 2022 01:40:23 GMT-07:00

Dual RAAS Blockade in CKD: Does the Hype have Teeth?

Chávez-Íñiguez, Jonathan S. — Tue, 19 Apr 2022 11:31:32 GMT-07:00

Hypernatremia in Hospitalized Patients: A Large Population-Based Study

Arzhan, Soraya — Wed, 20 Apr 2022 11:26:08 GMT-07:00

“Kidney Brothers”: The Case for Peer Support in Kidney Transplant

Shi, Audrey A. — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Is There One Best Way to Define AKI?

Zelnick, Leila R. — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Outcomes Associated with Hypernatremia at Admission in Hospitalized Persons

Tucker, Bryan M. — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study

Drawz, Paul E. — Tue, 10 May 2022 05:04:57 GMT-07:00

Stromal Transcription Factor 21 Regulates Development of the Renal Stroma via Interaction with Wnt/β-Catenin Signaling

Finer, Gal — Fri, 06 May 2022 01:23:10 GMT-07:00

Global Dialysis Perspective: Egypt

Farag, Youssef M.K. — Wed, 20 Apr 2022 11:26:08 GMT-07:00

Urinary Sulfate, Kidney Failure, and Death in CKD: The African American Study of Kidney Disease and Hypertension

Azim, Aniqa — Wed, 27 Apr 2022 09:28:29 GMT-07:00

Fluid Collection after Kidney Transplantation

Deneault-Marchand, Ariane — Thu, 28 Jul 2022 04:30:26 GMT-07:00

ASK1 Inhibitor in Chronic Kidney Disease Therapy: From Bench to Bedside

Wen, Lu — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Susceptibility to Environmental Heavy Metal Toxicity among Americans with Kidney Disease

Danziger, John — Fri, 29 Apr 2022 11:23:35 GMT-07:00

Do Proton-Pump Inhibitors Cause CKD and Progression of CKD?: COMMENTARY

Paueksakon, Paisit — Tue, 04 Jan 2022 05:02:17 GMT-08:00

Towards a Better Crystal Ball: Urinary C-C Motif Chemokine Ligand 14 (CCL14) and Persistent Severe AKI

Belcher, Justin M. — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Do Proton-Pump Inhibitors Cause CKD and Progression of CKD?: CON

Cholin, Liza — Tue, 04 Jan 2022 05:02:17 GMT-08:00

Using Human-Centered Design Principles to Create a Decision Aid on Conservative Kidney Management for Advanced Kidney Disease

Wong, Susan P.Y. — Wed, 11 May 2022 11:27:42 GMT-07:00

Levels of Lead in Residential Drinking Water and Iron Deficiency among Patients with End Stage Kidney Disease

Danziger, John — Fri, 29 Apr 2022 01:39:11 GMT-07:00

Performance of a Standardized Clinical Assay for Urinary C–C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury

Koyner, Jay L. — Fri, 25 Mar 2022 06:30:39 GMT-07:00

Acute Kidney Injury in a CKD Patient with a Prolapsed Uterus

Sakamoto, Sumie — Thu, 28 Jul 2022 04:30:26 GMT-07:00

Point-of-Care Testing: Home Is Where the Lab Is

Stauss, Madelena — Wed, 11 May 2022 01:40:23 GMT-07:00

Temporal Changes in Electrolytes, Acid-Base, QTc Duration, and Point-of-Care Ultrasound during Inpatient Hemodialysis Sessions

Ravi, Katherine Scovner — Tue, 10 May 2022 05:04:57 GMT-07:00

Selonsertib Enhances Kidney Protection Beyond Standard of Care in a Hypertensive, Secondary Glomerulosclerosis CKD Model

Badal, Shawn S. — Mon, 11 Apr 2022 11:55:37 GMT-07:00

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

vbhalla@stanford.edu — Tue, 19 Jul 2022 01:29:42 GMT-07:00

Background: Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. Methods: Using hydrodynamic tail-vein injection, we over-express Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli. Results: In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that over-expression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease-promoting and interferon-related genes, including Ackr2 and Cxcl11. Conclusions: We demonstrate that in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select interferon signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.

Management of Intermittent Hemodialysis in the Critically Ill Patient

Chan, Ryan J. — Fri, 15 Jul 2022 10:44:05 GMT-07:00

Intermittent hemodialysis remains a cornerstone of extracorporeal KRT in the intensive care unit, either as a first-line therapy for AKI or a second-line therapy when patients transition from a continuous or prolonged intermittent therapy. Intermittent hemodialysis is usually provided 3 days per week in this setting on the basis that no clinical benefits have been demonstrated with more frequent hemodialysis. This should not detract from the importance of continually assessing and refining the hemodialysis prescription (including the need for extra treatments) according to dynamic changes in extracellular volume and other parameters, and ensuring that an adequate dose of hemodialysis is being delivered to the patient. Compared with other KRT modalities, the cardinal challenge encountered during intermittent hemodialysis is hemodynamic instability. This phenomenon occurs when reductions in intravascular volume, as a consequence of ultrafiltration and/or osmotic shifts, outpace compensatory plasma refilling from the extravascular space. Myocardial stunning, triggered by intermittent hemodialysis, and independent of ultrafiltration, may also contribute. The hemodynamic effect of intermittent hemodialysis is likely magnified in patients who are critically ill due to an inability to mount sufficient compensatory physiologic responses in the context of multiorgan dysfunction. Of the many interventions that have undergone testing to mitigate hemodynamic instability related to KRT, the best evidence exists for cooling the dialysate and raising the dialysate sodium concentration. Unfortunately, the evidence supporting routine use of these and other interventions is weak owing to poor study quality and limited sample sizes. Intermittent hemodialysis will continue to be an important and commonly used KRT modality for AKI in patients with critical illness, especially in jurisdictions where resources are limited. There is an urgent need to harmonize the definition of hemodynamic instability related to KRT in clinical trials and robustly test strategies to combat it in this vulnerable patient population.

Addressing “Second Hits” in the Pursuit of Greater Equity in Health Outcomes for Individuals with ADPKD

Mohottige, Dinushika — Mon, 20 Jun 2022 11:03:59 GMT-07:00

Disentangling a Case of Glomerulonephritis with Fibrils

Canetta, Pietro — Thu, 02 Jun 2022 08:32:55 GMT-07:00

Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Caravaca-Fontán, Fernando — Fri, 01 Jul 2022 06:35:27 GMT-07:00

Engaging Trainees by Enriching Nephrology Elective Experiences

William, Jeffrey H. — Tue, 22 Mar 2022 07:37:41 GMT-07:00

Mitochondrial DNA and Kidney Function

nephro-intensiv@charite.de — Fri, 01 Jul 2022 06:35:27 GMT-07:00

Urine or You’re Out?

Harer, Matthew W. — Tue, 28 Jun 2022 11:18:08 GMT-07:00

Chlorthalidone and Advanced Chronic Kidney Disease

Furgeson, Seth B. — Mon, 16 May 2022 08:58:35 GMT-07:00

Machine Learning–Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients

Hong, Namki — Fri, 10 Jun 2022 05:55:26 GMT-07:00

Moving from Evidence to Implementation of Breakthrough Therapies for Diabetic Kidney Disease

Tuttle, Katherine R. — Wed, 01 Jun 2022 11:56:25 GMT-07:00

Diabetic kidney disease is the most frequent cause of kidney failure, accounting for half of all cases worldwide. Moreover, deaths from diabetic kidney disease increased 106% between 1990 and 2013, with most attributed to cardiovascular disease. Recommended screening and monitoring for diabetic kidney disease are conducted in less than half of patients with diabetes. Standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker is correspondingly low. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid antagonist are highly effective therapies to reduce kidney and cardiovascular risks in diabetic kidney disease. However, <20% of eligible patients are receiving these agents. Critical barriers are high out-of-pocket drug costs and low reimbursement rates. Data demonstrating clinical and cost-effectiveness of diabetic kidney disease care are needed to garner payer and health care system support. The pharmaceutical industry should collaborate on value-based care by increasing access through affordable drug prices. Additionally, multidisciplinary models and communication technologies tailored to individual health care systems are needed to support optimal diabetic kidney disease care. Community outreach efforts are also central to make care accessible and equitable. Finally, it is imperative that patient preferences and priorities shape implementation strategies. Access to care and implementation of breakthrough therapies for diabetic kidney disease can save millions of lives by preventing kidney failure, cardiovascular events, and premature death. Coalitions composed of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers are essential to develop collaborative models that successfully address this major public health challenge.

Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2– Recovered Dialysis Patients

Attias, Philippe — Tue, 28 Jun 2022 11:05:04 GMT-07:00

Glomerular Exostosin as a Subtype and Activity Marker of Class 5 Lupus Nephritis

Wang, Chengyu — Wed, 18 May 2022 10:59:11 GMT-07:00

Treatment Decision Making for Older Kidney Patients during COVID-19

Porteny, Thalia — Tue, 07 Jun 2022 05:24:39 GMT-07:00

Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney Disease

He, William J. — Fri, 01 Jul 2022 06:35:27 GMT-07:00

Low-Flow Acute Kidney Injury

Molitoris, Bruce A. — Wed, 18 May 2022 10:59:11 GMT-07:00

AKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.

The Pathophysiology of Sepsis-Associated AKI

Kuwabara, Shuhei — Tue, 28 Jun 2022 11:05:04 GMT-07:00

Sepsis-associated AKI is a life-threatening complication that is associated with high morbidity and mortality in patients who are critically ill. Although it is clear early supportive interventions in sepsis reduce mortality, it is less clear that they prevent or ameliorate sepsis-associated AKI. This is likely because specific mechanisms underlying AKI attributable to sepsis are not fully understood. Understanding these mechanisms will form the foundation for the development of strategies for early diagnosis and treatment of sepsis-associated AKI. Here, we summarize recent laboratory and clinical studies, focusing on critical factors in the pathophysiology of sepsis-associated AKI: microcirculatory dysfunction, inflammation, NOD-like receptor protein 3 inflammasome, microRNAs, extracellular vesicles, autophagy and efferocytosis, inflammatory reflex pathway, vitamin D, and metabolic reprogramming. Lastly, identifying these molecular targets and defining clinical subphenotypes will permit precision approaches in the prevention and treatment of sepsis-associated AKI.

Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United States

McGill, Rita L. — Mon, 20 Jun 2022 11:03:59 GMT-07:00

Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm Infants

aureliedemul@gmail.com — Tue, 28 Jun 2022 11:18:09 GMT-07:00

SARS-CoV-2 Booster Vaccine Response among Patients Receiving Dialysis

Garcia, Pablo — Tue, 05 Apr 2022 09:51:00 GMT-07:00

Lifesaving Care for Patients with Kidney Failure during the War in Ukraine 2022

Stepanova, Natalia — Tue, 10 May 2022 06:43:13 GMT-07:00

Keys to Driving Implementation of the New Kidney Care Models

Kshirsagar, Abhijit V. — Mon, 14 Mar 2022 05:54:39 GMT-07:00

Contemporary nephrology practice is heavily weighted toward in-center hemodialysis, reflective of decisions on infrastructure and personnel in response to decades of policy. The Advancing American Kidney Health initiative seeks to transform care for patients and providers. Under the initiative’s framework, the Center for Medicare and Medicaid Innovation has launched two new care models that align patient choice with provider incentives. The mandatory ESRD Treatment Choices model requires participation by all nephrology practices in designated Hospital Referral Regions, randomly selecting 30% of all Hospital Referral Regions across the United States for participation, with the remaining Hospital Referral Regions serving as controls. The voluntary Kidney Care Choices model offers alternative payment programs open to nephrology practices throughout the country. To help organize implementation of the models, we developed Driver Diagrams that serve as blueprints to identify structures, processes, and norms and generate intervention concepts. We focused on two goals that are directly applicable to nephrology practices and central to the incentive structure of the ESRD Treatment Choices and Kidney Care Choices: (1) increasing utilization of home dialysis, and (2) increasing the number of kidney transplants. Several recurring themes became apparent with implementation. Multiple stakeholders from assorted backgrounds are needed. Communication with primary care providers will facilitate timely referrals, education, and comanagement. Nephrology providers (nephrologists, nursing, dialysis organizations, others) must lead implementation. Patient engagement at nearly every step will help achieve the aims of the models. Advocacy with federal and state regulatory agencies will be crucial to expanding home dialysis and transplantation access. Although the models hold promise to improve choices and outcomes for many patients, we must be vigilant that they not do reinforce existing disparities in health care or widen known racial, socioeconomic, or geographic gaps. The Advancing American Kidney Health initiative has the potential to usher in a new era of value-based care for nephrology.

Changing Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Ruff, Suzanne F. — Mon, 20 Jun 2022 10:42:35 GMT-07:00

Automated Determination of Left Ventricular Function Using Electrocardiogram Data in Patients on Maintenance Hemodialysis

Vaid, Akhil — Mon, 06 Jun 2022 09:20:13 GMT-07:00

Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Lomax-Browne, Hannah J. — Fri, 01 Jul 2022 06:35:28 GMT-07:00

United States Renal Data System Spotlight on Racial and Ethnic Health Equity: Progress, but Much Remains to Discover, Understand, and Improve

Johansen, Kirsten L. — Tue, 21 Jun 2022 07:17:29 GMT-07:00

Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 Autoantibodies

Figueres, Lucile — Tue, 21 Jun 2022 07:17:27 GMT-07:00

Predicting Future Outcomes from Kidney Biopsies with MCD/FSGS Lesions: Opportunities and Limitations

Anders, Hans-Joachim — Tue, 21 Jun 2022 07:17:29 GMT-07:00

Looking Upstream–The Role of Primary Care in Addressing US Race Inequities in Kidney Health

Boulware, L. Ebony — Tue, 21 Jun 2022 07:17:30 GMT-07:00

Recognizing the Potential Importance of Religion and Spirituality in the Care of Black Americans with Kidney Failure

Gelfand, Samantha L. — Fri, 18 Mar 2022 05:24:43 GMT-07:00

Kidney Health Disparities: The Goal is Elimination

Wesson, Donald E. — Tue, 21 Jun 2022 07:17:28 GMT-07:00

Equitable Transplantation: A Modifiable Risk Factor for Disparities in Mortality in ESKD

Laster, Marciana — Fri, 01 Apr 2022 05:41:05 GMT-07:00

Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients

Oka, Yoshinari — Mon, 02 May 2022 08:50:15 GMT-07:00

Authors’ Reply: Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients

Pfau, Anja — Mon, 02 May 2022 08:35:35 GMT-07:00

Kidney Biopsy Features Most Predictive of Clinical Outcomes in the Spectrum of Minimal Change Disease and Focal Segmental Glomerulosclerosis

Zee, Jarcy — Tue, 17 May 2022 12:16:15 GMT-07:00

The Association of Excess Body Weight with Risk of ESKD Is Mediated Through Insulin Resistance, Hypertension, and Hyperuricemia

Fritz, Josef — Mon, 02 May 2022 07:30:08 GMT-07:00

Aqp2+ Progenitor Cells Maintain and Repair Distal Renal Segments

Gao, Chao — Tue, 22 Mar 2022 10:39:15 GMT-07:00

Navigating to Kidney Health Equity

Griffith, Derek M. — Tue, 21 Jun 2022 07:17:29 GMT-07:00

Lack of Cultural and Language Concordant Nutrition Education for Hispanic/Latinx Individuals with CKD: A Call to Action

Perez, Luis M. — Wed, 11 May 2022 08:24:36 GMT-07:00

Association of Proximal Tubular Secretory Clearance with Long-Term Decline in Cognitive Function

Lidgard, Benjamin — Wed, 20 Apr 2022 10:34:28 GMT-07:00

Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells

Schepelmann, Martin — Tue, 17 May 2022 12:16:14 GMT-07:00

Racial and Ethnic Disparities in Home Dialysis Use in the United States: Barriers and Solutions

Rizzolo, Katherine — Tue, 19 Apr 2022 09:24:58 GMT-07:00

Culturally Concordant Community-Health Workers: Building Sustainable Community-Based Interventions that Eliminate Kidney Health Disparities

Cervantes, Lilia — Tue, 26 Apr 2022 09:13:40 GMT-07:00

Authors’ Reply: Clinical Studies of Vaccine Efficacy

Bell, Samira — Tue, 21 Jun 2022 07:17:29 GMT-07:00

A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection

Hassler, Luise — Wed, 02 Mar 2022 09:47:43 GMT-08:00

Clinical Studies of Vaccine Efficacy

Ashby, Damien — Tue, 21 Jun 2022 07:17:30 GMT-07:00

Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis

Smeets, Nori J.L. — Tue, 26 Apr 2022 09:13:40 GMT-07:00

Transplantation Mediates Much of the Racial Disparity in Survival from Childhood-Onset Kidney Failure

Becerra, Adan Z. — Tue, 25 Jan 2022 09:43:22 GMT-08:00

Single-Cell Chromatin and Gene-Regulatory Dynamics of Mouse Nephron Progenitors

Hilliard, Sylvia — Tue, 05 Apr 2022 12:39:29 GMT-07:00

Brief Early Life Angiotensin-Converting Enzyme Inhibition Offers Renoprotection in Sheep with a Solitary Functioning Kidney at 8 Months of Age

McArdle, Zoe — Tue, 29 Mar 2022 08:10:44 GMT-07:00

Autoimmune Renal Calcium and Magnesium Wasting

Schlingmann, Karl P. — Tue, 21 Jun 2022 07:17:28 GMT-07:00

GFR and eGFR in Term-Born Neonates

Filler, Guido — Tue, 21 Jun 2022 07:17:27 GMT-07:00

This Month's Highlights

American Society of Nephrology — Thu, 30 Jun 2022 10:00:27 GMT-07:00

Association of the Comprehensive ESRD Care Model with Treatment Adherence

Hirth, Richard A. — Tue, 21 Dec 2021 11:52:25 GMT-08:00

Hemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart Failure

Maulion, Christopher — Tue, 12 Apr 2022 07:48:45 GMT-07:00

Cardiopulmonary Resuscitation in US Dialysis Clinics: Room for Improvement

Yap, Ernie — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Painful Leg Ulcers in an ESKD Patient

Fernandes, Sara — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? CON

Cheng, Xingxing S. — Fri, 15 Oct 2021 09:31:44 GMT-07:00

Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? PRO

Truong, Tiffany T. — Fri, 15 Oct 2021 09:31:44 GMT-07:00

The Clinical Utility of the Neutrophil-to-Lymphocyte Ratio as a Discriminatory Test among Bacterial, Mycobacterium Tuberculosis, and Nontuberculous Mycobacterium Peritoneal Dialysis–Related Peritonitis

Fung, Winston Wing-Shing — Tue, 29 Mar 2022 11:45:29 GMT-07:00

Central Venous Catheter Versus Permanent Access: A Hemodialysis Patient Focus Group

Davis, Jane S. — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Pretransplant Dialysis and Preemptive Transplant in Living Donor Kidney Recipients

Lai, Mason — Mon, 11 Apr 2022 11:55:37 GMT-07:00

An Unusual Kidney Lesion Presenting with Facial Edema, Hematuria, and AKI

Bond, Tanner — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? COMMENTARY

Asch, William S. — Fri, 15 Oct 2021 09:31:44 GMT-07:00

Does More Serum Creatinine Really Just Mean Less Volume?

Kula, Alexander J. — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Differential Impact of Central Venous Catheters versus Arteriovenous Fistulae on Quality of Life among Irish Haemodialysis Patients

Maguire, I. Caoimhe — Fri, 04 Mar 2022 11:28:48 GMT-08:00

The Forgotten Cost of Nephrotic Syndrome to Patients and Caregivers in the United States

Rajasekaran, Arun — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Facility-Level Factors and Racial Disparities in Cardiopulmonary Resuscitation within US Dialysis Clinics

Pun, Patrick H. — Fri, 11 Mar 2022 08:00:09 GMT-08:00

Arteriovenous Fistula or Dialysis Catheter: A Patient’s Perspective

Gedney, Nieltje — Fri, 15 Apr 2022 01:32:21 GMT-07:00

Ongoing Lessons from the Comprehensive ESRD Care Program

Kinlaw, Alan C. — Thu, 30 Jun 2022 06:00:22 GMT-07:00

Utilization of Peritoneal Dialysis in the United States: Progress in Tackling Obstacles to Expansion

El Shamy, Osama — Fri, 15 Apr 2022 01:32:21 GMT-07:00

To facilitate the desired increase in home dialysis utilization in the United States, multiple factors need to be taken into consideration in order to achieve this complex task. Through policy-level facilitators such as the Advancing American Kidney Health Initiative and the expansion of telehealth utilization, adjustments to the existing payment models, providing health equity incentives, increasing number of provider education materials on home therapies, and allaying patient fears with the expansion of home dialysis education nationwide, we have taken several steps in the right direction. There is still a long way to go, and further improvements can be made while utilizing lessons learned from some of our international peers who have been successful in their implementation of large-scale home dialysis programs.

Global Dialysis Perspective: Haiti

Exantus, Judith — Tue, 29 Mar 2022 02:35:44 GMT-07:00

Exacerbation of Racial Disparities in Living Donor Kidney Transplantation During the COVID-19 Pandemic

Singh, Neeraj — Thu, 05 May 2022 01:22:35 GMT-07:00

The Impact of COVID-19 on Postdischarge Outcomes for Dialysis Patients in the United States: Evidence from Medicare Claims Data

Wu, Wenbo — Fri, 15 Apr 2022 01:32:21 GMT-07:00

Lived Experiences of Patients Receiving Hemodialysis during the COVID-19 Pandemic: A Qualitative Study from the Quebec Renal Network

Malo, Marie-Françoise — Mon, 25 Apr 2022 01:37:01 GMT-07:00

The Health Economic Impact of Nephrotic Syndrome in the United States

Simon, Christine A. — Mon, 25 Apr 2022 01:37:01 GMT-07:00

Urinary Polycyclic Aromatic Hydrocarbons in a Longitudinal Cohort of Children with CKD: A Case of Reverse Causation?

Jacobson, Melanie H. — Tue, 29 Mar 2022 02:35:44 GMT-07:00

Global Perspectives in Acute Kidney Injury: Japan

Yamada, Hiroyuki — Tue, 29 Mar 2022 02:35:44 GMT-07:00

Global Perspectives in Acute Kidney Injury: Ireland

Redahan, Lynn — Thu, 21 Apr 2022 10:37:49 GMT-07:00

Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney Injury

Abdelhafez, Mohammad — Wed, 11 May 2022 01:53:24 GMT-07:00

PCSK9 and Cardiovascular Disease in Individuals with Moderately Decreased Kidney Function

Kheirkhah, Azin — Wed, 06 Apr 2022 09:26:24 GMT-07:00

Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice Guideline

Murayama, Anju — Fri, 27 May 2022 10:37:42 GMT-07:00

Medicare Bundled Payment Policy on Anemia Care, Major Adverse Cardiovascular Events, and Mortality among Adults Undergoing Hemodialysis

Park, Haesuk — Thu, 19 May 2022 11:31:15 GMT-07:00

Variation in Peritoneal Dialysis Time on Therapy by Country

Lambie, Mark — Tue, 31 May 2022 12:48:45 GMT-07:00

Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations

Brandenburg, Jean-Tristan — Mon, 16 May 2022 08:58:36 GMT-07:00

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy

Uppal, Nupur N. — Fri, 21 Jan 2022 07:16:21 GMT-08:00

Novel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all types of cancers. Immune-related adverse events have been associated with immunotherapies. AKI has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor–induced parathyroid hormone–related peptide production, sarcoid-like granulomas, and hyperprogression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor–induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy–associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.

Mechanical Circulatory Support

Tam, Christopher W. — Fri, 20 May 2022 09:56:38 GMT-07:00

Mechanical life support therapies exist in many forms to temporarily replace the function of vital organs. Generally speaking, these tools are supportive therapy to allow for organ recovery but, at times, require transition to long-term mechanical support. This review will examine nonrenal extracorporeal life support for cardiac and pulmonary support as well as other mechanical circulatory support options. This is intended as a general primer and overview to assist nephrologist consultants participating in the care of these critically ill patients who often experience acute renal injury as a result of cardiopulmonary shock and from their exposure to mechanical circulatory support.

Endothelin Receptor Antagonists for Kidney Protection

Heerspink, Hiddo J.L. — Thu, 28 Apr 2022 09:27:02 GMT-07:00

Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison with Magnetic Resonance Imaging

Akbari, Pedram — Tue, 05 Apr 2022 09:51:00 GMT-07:00

Sepsis Management for the Nephrologist

Patel, Sharad — Thu, 12 May 2022 08:19:26 GMT-07:00

The definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion leading to end organ dysfunction. Septic shock is characterized by hypotension requiring vasopressors after adequate fluid resuscitation with elevated lactate. Early recognition and intervention remain hallmarks for sepsis management. We addressed the current literature and assimilated thought regarding optimum initial resuscitation of the patient with sepsis. A nuanced understanding of the physiology of lactate is provided in our review. Physiologic and practical knowledge of steroid and vasopressor therapy for sepsis is crucial and addressed. As blood purification may interest the nephrologist treating sepsis, we have also added a brief discussion of its status.

Conflicts of Interest and the Trustworthiness of Clinical Practice Guidelines

Mathew, Anna — Fri, 27 May 2022 10:37:42 GMT-07:00

Cannabinoids for Symptom Management in Patients with Kidney Failure

Worth, Hayley — Wed, 05 Jan 2022 10:13:41 GMT-08:00

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, antiemetic, analgesic, and anti-inflammatory effects. Considering their known physiologic actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, although these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.

Statement of Clarification: Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug Use

American Society of Nephrology — Wed, 18 May 2022 10:59:11 GMT-07:00

Hypertension with Kidney Failure

Rivara, Matthew B. — Mon, 28 Mar 2022 05:07:18 GMT-07:00

Medicare Bundled Payment Policy and Anemia Care

Thomas, Cher — Thu, 19 May 2022 11:31:15 GMT-07:00

Fractional Excretion of Sodium (FENa)

Seethapathy, Harish — Wed, 25 May 2022 11:01:49 GMT-07:00

International Variation in Time on Peritoneal Dialysis

Rivara, Matthew B. — Tue, 31 May 2022 12:48:45 GMT-07:00

Safety of SGLT2 Inhibitors in CKD

Dobre, Mirela — Thu, 26 May 2022 07:04:51 GMT-07:00

Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease

Cowan, Andrea — Thu, 26 May 2022 07:04:52 GMT-07:00

COVID-19 Vaccination for Patients Undergoing Long-Term Hemodialysis

Korst, Uwe K.H. — Wed, 01 Jun 2022 11:44:27 GMT-07:00

Humoral Response to Third Dose of SARS-CoV-2 Vaccines in the CKD Spectrum

Quiroga, Borja — Thu, 12 May 2022 08:19:26 GMT-07:00

Clinical Utility of COVID-19 Vaccination in Patients Undergoing Hemodialysis

Oliver, Matthew J. — Wed, 01 Jun 2022 11:44:27 GMT-07:00

Severity of COVID-19 after Vaccination among Hemodialysis Patients

Ashby, Damien R. — Wed, 01 Jun 2022 11:44:27 GMT-07:00

Correction: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial

American Society of Nephrology — Fri, 20 May 2022 09:56:37 GMT-07:00

The Role of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists in the Prevention and Treatment of Diabetic Kidney Disease

Tommerdahl, Kalie L. — Fri, 08 Apr 2022 07:31:44 GMT-07:00

Cerebral salt wasting is a real cause of hyponatremia: CON

rondonberriosh@upmc.edu — Thu, 02 Jun 2022 10:04:41 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the COMMENTARY: 10.34067/KID.0001452022

Cerebral salt wasting is a real cause of hyponatremia: PRO

John.Maesaka@nyulangone.org — Thu, 02 Jun 2022 10:04:41 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0001412022 and the COMMENTARY: 10.34067/KID.0001452022

Cerebral salt wasting is a real cause of hyponatremia: Commentary

biff.palmer@utsouthwestern.edu — Thu, 02 Jun 2022 10:04:41 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the CON: 10.34067/KID.0001412022

More than a Marker: Arginase-1 in Kidney Repair

von Vietinghoff, Sibylle — Mon, 16 May 2022 11:58:01 GMT-07:00

Crystals or His(stones): Rethinking AKI in Tumor Lysis Syndrome

Basile, David P. — Tue, 31 May 2022 10:00:28 GMT-07:00

This Month's Highlights

American Society of Nephrology — Tue, 31 May 2022 10:00:28 GMT-07:00

Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma Exchange

Casal Moura, Marta — Mon, 11 Apr 2022 11:45:23 GMT-07:00

Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy

Márquez-Tirado, Bárbara — Wed, 11 May 2022 01:54:29 GMT-07:00

Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC Study

McCoy, Ian E. — Wed, 16 Mar 2022 08:07:05 GMT-07:00

Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study

Knoll, Greg — Wed, 23 Mar 2022 10:18:25 GMT-07:00

Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United States

Baerman, Elliot A. — Mon, 21 Mar 2022 08:02:49 GMT-07:00

The United States Department of Health and Human Services launched the Advancing American Kidney Health Initiative in 2019, which included a goal of transforming dialysis care from an in-center to a largely home-based dialysis program. A substantial motivator for this transition is the potential to reduce costs of ESKD care with peritoneal dialysis. Studies demonstrating that peritoneal dialysis is less costly than in-center hemodialysis have often focused on the perspective of the payer, whereas less consideration has been given to the costs of those who are more directly involved in treatment decision making, including patients, caregivers, physicians, and dialysis facilities. We review comparisons of peritoneal dialysis and in-center hemodialysis costs, focusing on costs incurred by the people and organizations making decisions about dialysis modality, to highlight the financial barriers toward increased adoption of peritoneal dialysis. We specifically address misaligned economic incentives, underappreciated costs for key stakeholders involved in peritoneal dialysis delivery, differences in provider costs, and transition costs. We conclude by offering policy suggestions that include improving data collection to better understand costs in peritoneal dialysis, and sharing potential savings among all stakeholders, to incentivize a transition to peritoneal dialysis.

The Advancing American Kidney Health Initiative: The Challenge of Measuring Success

Quinn, Robert R. — Tue, 29 Mar 2022 08:10:44 GMT-07:00

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Chan, Eugene Yu-hin — Wed, 30 Mar 2022 10:11:26 GMT-07:00

Authors’ Reply: Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma Exchange

Nezam, Dorian — Mon, 11 Apr 2022 11:29:40 GMT-07:00

Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms

Arnaud, Marine — Fri, 06 May 2022 11:20:43 GMT-07:00

Unveiling the Role of Additional Histological Parameters in ANCA-Associated Vasculitis

L’Imperio, Vincenzo — Fri, 08 Apr 2022 08:35:43 GMT-07:00

Protein Kinase A Downregulation Delays the Development and Progression of Polycystic Kidney Disease

Wang, Xiaofang — Wed, 02 Mar 2022 09:47:43 GMT-08:00

Molecular Characterization of Membranous Nephropathy: Quo Vadis?

Fervenza, Fernando C. — Mon, 16 May 2022 02:13:38 GMT-07:00

Correction: The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland

American Society of Nephrology — Tue, 31 May 2022 10:00:28 GMT-07:00

Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration

Shin, Naomi S. — Mon, 16 May 2022 01:17:09 GMT-07:00

Molecular Characterization of Membranous Nephropathy

Sealfon, Rachel — Wed, 27 Apr 2022 08:25:13 GMT-07:00

Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease

Linh, Hoang Thuy — Wed, 09 Mar 2022 07:41:00 GMT-08:00

Reduced Glomerular Filtration in Diabetes Is Attributable to Loss of Density and Increased Resistance of Glomerular Endothelial Cell Fenestrations

Finch, Natalie C. — Tue, 15 Mar 2022 08:38:02 GMT-07:00

Of Mice and MAVS–Diabetic Kidney Disease and the Leaky Gut

Farré, Ricard — Tue, 31 May 2022 10:00:28 GMT-07:00

Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate

Harmacek, Dusan — Wed, 06 Apr 2022 08:47:59 GMT-07:00

Clinical Trial registry name and registration number: Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN), NCT03093103

A Call for Implementation Science: Achieving Equitable Access to SGLT2 Inhibitors

Claudel, Sophie E. — Wed, 02 Mar 2022 12:39:24 GMT-08:00

Global Perspectives in Acute Kidney Injury: Canada

Silver, Samuel A. — Tue, 08 Mar 2022 01:04:13 GMT-08:00

uEVs: A Potential Tool for Examining Renal Epithelial Cells

Deck, Katherine S. — Thu, 26 May 2022 12:30:28 GMT-07:00

Cardiac Biomarkers and Risk of Atherosclerotic Cardiovascular Disease in Patients with CKD

Lidgard, Benjamin — Wed, 02 Mar 2022 12:39:24 GMT-08:00

Global Dialysis Perspective: Uganda

Kalyesubula, Robert — Thu, 03 Mar 2022 09:53:41 GMT-08:00

AKI in a Kidney Transplant Patient on a High-Risk Immunologic Drug Protocol

gstarkell@eoarla.ca — Thu, 26 May 2022 12:30:28 GMT-07:00

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles

Wu, Aihua — Wed, 02 Mar 2022 03:59:15 GMT-08:00

Icodextrin in Peritoneal Dialysis: Implications on Clinical Practice and Survival Outcome

Ng, Jack Kit-Chung — Thu, 26 May 2022 12:30:28 GMT-07:00

Hidden Costs Associated with Conversion from Peritoneal Dialysis to Hemodialysis

Weinhandl, Eric D. — Thu, 03 Mar 2022 06:46:18 GMT-08:00

Impact of Medication Reconciliation by a Dialysis Pharmacist

Dyer, Summer A. — Fri, 25 Mar 2022 11:44:50 GMT-07:00

F4/80hi Resident Macrophages Contribute to Cisplatin-Induced Renal Fibrosis

Sears, Sophia M. — Thu, 10 Feb 2022 01:27:49 GMT-08:00

Dialysis Catheter Site-Related Tenderness and Erythema

Ono, Keisuke — Thu, 26 May 2022 12:30:28 GMT-07:00

Circulating Levels of Endotrophin Are Prognostic for Long-Term Mortality after AKI

Sparding, Nadja — Thu, 03 Mar 2022 09:53:41 GMT-08:00

County-Level Characteristics Associated with Variation in ESKD Mortality in the United States, 2010–2018

Snow, Kylie K. — Thu, 03 Mar 2022 09:53:41 GMT-08:00

International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique Survival

Davies, Simon — Tue, 01 Mar 2022 11:54:15 GMT-08:00

Measurement of Urinary Ammonium Using a Commercially Available Plasma Ammonium Assay

Gruzdys, Valentinas — Fri, 11 Feb 2022 05:52:12 GMT-08:00

Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome

Cox, Zachary L. — Tue, 01 Mar 2022 01:34:06 GMT-08:00

Despite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium avidity. The underlying level of renal sodium avidity is of primary importance in driving a congested heart failure phenotype and ultimately determining the response to diuretic therapy. Historically, mechanisms of kidney sodium avidity and resultant diuretic resistance were primarily extrapolated to cardiorenal syndrome from non–heart failure populations. Yet, the mechanisms appear to differ between these populations. Recent literature in acute decompensated heart failure has refuted several classically accepted diuretic resistance mechanisms and reshaped how we conceptualize diuretic resistance mechanisms in cardiorenal syndrome. Herein, we propose an anatomically based categorization of diuretic resistance mechanisms to establish the relative importance of specific transporters and translate findings toward therapeutic strategies. Within this categorical structure, we discuss classic and novel mechanisms of diuretic resistance.

Profiling Immune Cells in the Kidney Using Tissue Cytometry and Machine Learning

telachka@iu.edu — Thu, 11 Feb 2021 09:46:02 GMT-08:00

The immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic stress and injury. We increasingly recognize that microenvironments within the kidney are characterized by a unique distribution of immune cells, the function of which depends on this unique spatial localization. Therefore, quantitative profiling of immune cells in intact kidney tissue becomes essential, particularly at a scale and resolution that allow the detection of differences between the various “nephro-ecosystems” in health and disease. In this review, we discuss advancements in tissue cytometry of the kidney, performed through multiplexed confocal imaging and analysis using the Volumetric Tissue Exploration and Analysis (VTEA) software. We highlight how this tool has improved our understanding of the role of the immune system in the kidney and its relevance in the pathobiology of renal disease. We also discuss how the field is increasingly incorporating machine learning to enhance the analytic potential of imaging data and provide unbiased methods to explore and visualize multidimensional data. Such novel analytic methods could be particularly relevant when applied to profiling immune cells. Furthermore, machine-learning approaches applied to cytometry could present venues for nonexhaustive exploration and classification of cells from existing data and improving tissue economy. Therefore, tissue cytometry is transforming what used to be a qualitative assessment of the kidney into a highly quantitative, imaging-based “omics” assessment that complements other advanced molecular interrogation technologies.

The KIDNEYCODE Program: Diagnostic Yield and Clinical Features of Individuals with CKD

Lieberman, Kenneth V. — Thu, 10 Mar 2022 09:27:38 GMT-08:00

Rates of Cardiovascular Disease and CKD Progression in Young Adults with CKD across Racial and Ethnic Groups

Kula, Alexander J. — Thu, 17 Feb 2022 11:48:22 GMT-08:00

Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKD

Momb, Brent A. — Fri, 25 Mar 2022 11:44:50 GMT-07:00

Novel Function for Bilirubin as a Metabolic Signaling Molecule: Implications for Kidney Diseases

Stec, David E. — Fri, 25 Mar 2022 01:37:16 GMT-07:00

Bilirubin is the end product of the catabolism of heme via the heme oxygenase pathway. Heme oxygenase generates carbon monoxide (CO) and biliverdin from the breakdown of heme, and biliverdin is rapidly reduced to bilirubin by the enzyme biliverdin reductase (BVR). Bilirubin has long been thought of as a toxic product that is only relevant to health when blood levels are severely elevated, such as in clinical jaundice. The physiologic functions of bilirubin correlate with the growing body of evidence demonstrating the protective effects of serum bilirubin against cardiovascular and metabolic diseases. Although the correlative evidence suggests a protective effect of serum bilirubin against many diseases, the mechanism by which bilirubin offers protection against cardiovascular and metabolic diseases remains unanswered. We recently discovered a novel function for bilirubin as a signaling molecule capable of activating the peroxisome proliferator-activated receptor α (PPARα) transcription factor. This review summarizes the new finding of bilirubin as a signaling molecule and proposes several mechanisms by which this novel action of bilirubin may protect against cardiovascular and kidney diseases.

Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: COMMENTARY

Shirali, Anushree C. — Fri, 17 Sep 2021 11:21:16 GMT-07:00

Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: PRO

Herrmann, Sandra M. — Fri, 17 Sep 2021 11:21:16 GMT-07:00

Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: CON

Kanduri, Swetha Rani — Fri, 17 Sep 2021 11:21:16 GMT-07:00

Midodrine is an effective therapy for resistant intradialytic hypotension: COMMENTARY

tichang@stanford.edu — Wed, 11 May 2022 01:40:23 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the CON: 10.34067/KID.0007422021

Midodrine is an effective therapy for resistant intradialytic hypotension: PRO

Andrew.House@lhsc.on.ca — Wed, 11 May 2022 01:40:23 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007422021 and the COMMENTARY: 10.34067/KID.0007442021

Midodrine is an effective therapy for resistant intradialytic hypotension: CON

steven.brunelli@davita.com — Wed, 11 May 2022 01:40:23 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the COMMENTARY: 10.34067/KID.0007442021

Detecting and Treating Lung Congestion with Kidney Failure

Zoccali, Carmine — Wed, 09 Feb 2022 08:21:03 GMT-08:00

Fluid overload is a common complication in patients with CKD, particularly patients with kidney failure, a population with a very high risk for pulmonary edema. Lung ultrasound is now a well-validated technique that allows for reliable estimates of lung water in clinical practice. Several studies in patients with kidney failure documented a high prevalence of asymptomatic lung congestion of moderate to severe degree in this population, and this alteration was only weakly related with fluid excess as measured by bioimpedance spectroscopy. Furthermore, in these studies, lung congestion correlated in a dose-dependent fashion with death risk. In the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk Kidney Failure Patients with Cardiomyopathy (LUST) trial, a treatment strategy guided by lung ultrasound safely relieved lung congestion but failed to significantly reduce the risk for a combined end point including death, nonfatal myocardial infarction, and decompensated heart failure. However, in line with three trials in patients with heart failure, a post hoc analysis of the LUST trial showed that the use of lung ultrasound reduces the risk for repeated episodes of acute heart failure and repeated cardiovascular events. Given the high cardiovascular risk of pulmonary edema in patients with predialysis CKD, defining the epidemiology of lung congestion in this population is a public health priority. Specific trials in this population and additional trials in patients with kidney failure will establish whether targeting lung congestion at an asymptomatic phase may improve the severe cardiovascular prognosis of both patients predialysis and patients on dialysis.

Changing the Trajectory of Heart Failure and Kidney Disease

Rangaswami, Janani — Tue, 01 Mar 2022 07:47:45 GMT-08:00

Implementation of a Staff-Assisted Peritoneal Dialysis Program in the United States

Hussein, Wael F. — Tue, 05 Apr 2022 05:52:56 GMT-07:00

Mass Transport in High-Flux Hemodialysis

Mohajerani, Farzad — Fri, 11 Mar 2022 06:56:02 GMT-08:00

An understanding of the processes underlying mass transfer is paramount for the attainment of adequate solute removal in the dialytic treatment of patients with kidney failure. In this review, engineering principles are applied to characterize the physical mechanisms behind the two major modes of mass transfer during hemodialysis, namely diffusion and convection. The manner in which flow rate, dialyzer geometry, and membrane microstructure affect these processes is discussed, with concepts such as boundary layers, effective membrane diffusivity, and sieving coefficients highlighted as critical considerations. The objective is to improve clinicians’ understanding of these concepts as important factors influencing the prescription and delivery of hemodialysis therapy.

GWAS of Hematuria

Gagliano Taliun, Sarah A. — Tue, 26 Apr 2022 07:42:22 GMT-07:00

Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement Therapy

Thompson Bastin, Melissa L. — Wed, 27 Apr 2022 11:03:42 GMT-07:00

Functional Assessment of High-Risk APOL1 Genetic Variants

Robinson-Cohen, Cassianne — Tue, 26 Apr 2022 08:49:45 GMT-07:00

Recurrent Podocytopathy after Kidney Transplantation

Garg, Neetika — Fri, 25 Mar 2022 07:54:19 GMT-07:00

Treatment Options for Venous Thromboembolism in Patients Receiving Dialysis

Mavrakanas, Thomas A. — Mon, 25 Apr 2022 11:37:13 GMT-07:00

CRRT Fluid Choices

Vijayan, Anitha — Wed, 27 Apr 2022 11:42:51 GMT-07:00

APOL1 Kidney Risk Variants and Proteomics

Chen, Teresa K. — Tue, 26 Apr 2022 08:36:07 GMT-07:00

Provider Perspectives and Clinical Outcomes with Inpatient Telenephrology

Androga, Lagu A. — Wed, 23 Mar 2022 08:31:11 GMT-07:00

Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis

Wetmore, James B. — Mon, 25 Apr 2022 11:23:36 GMT-07:00

Learnings from Throwing Paint at the Wall for COVID-19 with an SGLT2 Inhibitor

Tuttle, Katherine R. — Thu, 28 Apr 2022 05:35:08 GMT-07:00

SARS-CoV-2 Vaccine Mandates for Patients on the Kidney Transplant Waitlist

Tallaa, Faissal — Wed, 02 Mar 2022 09:43:50 GMT-08:00

Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection

Heerspink, Hiddo J.L. — Thu, 28 Apr 2022 05:03:06 GMT-07:00

Overview of Diagnostic Criteria and Epidemiology of Acute Kidney Injury and Acute Kidney Disease in the Critically Ill Patient

Birkelo, Bethany C. — Tue, 15 Mar 2022 08:22:04 GMT-07:00

Since the description ischuria renalis by William Heberden (1), AKI has remained a prominent complication of critical illness. Beyond KRT, treatment has been limited by the capacity to phenotype this condition. Here, we chronicle the evolution of attempts to classify AKI, including the adoption of consensus definitions, the expansion of diagnosis and prognosis with novel biomarkers, and emerging tools such as artificial intelligence (AI).

The Intensivist's Perspective of Shock, Volume Management, and Hemodynamic Monitoring

Kashani, Kianoush — Mon, 04 Apr 2022 07:46:06 GMT-07:00

One of the primary reasons for intensive care admission is shock. Identifying the underlying cause of shock (hypovolemic, distributive, cardiogenic, and obstructive) may lead to entirely different clinical pathways for management. Among patients with hypovolemic and distributive shock, fluid therapy is one of the leading management strategies. Although an appropriate amount of fluid administration might save a patient's life, inadequate (or excessive) fluid use could lead to more complications, including organ failure and mortality due to either hypovolemia or volume overload. Currently, intensivists have access to a wide variety of information sources and tools to monitor the underlying hemodynamic status, including medical history, physical examination, and specific hemodynamic monitoring devices. Although appropriate and timely assessment and interpretation of this information can promote adequate fluid resuscitation, misinterpretation of these data can also lead to additional mortality and morbidity. This article provides a narrative review of the most commonly used hemodynamic monitoring approaches to assessing fluid responsiveness and fluid tolerance. In addition, we describe the benefits and disadvantages of these tools.

SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function

Suijk, Danii L.S. — Wed, 23 Mar 2022 08:31:11 GMT-07:00

The Transition of a Pediatric Kidney Transplant Recipient from Childhood to Adult Care

Bell, Lorraine E. — Fri, 11 Mar 2022 06:56:03 GMT-08:00

Author’s Reply: The Subcellular Localization of RRAGD

Schlingmann, Karl P. — Thu, 31 Mar 2022 08:11:18 GMT-07:00

Enabling Patient Choice: The “Deciding Not to Decide” Option for Older Adults Facing Dialysis Decisions

Saeed, Fahad — Tue, 15 Feb 2022 07:08:22 GMT-08:00

Authors’ Reply: More Research is Still Needed to Support the Real-World Generalizability of the Benefits of Lifestyle Interventions for Chronic Kidney Disease

Beetham, Kassia S. — Wed, 30 Mar 2022 08:09:48 GMT-07:00

Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D

Chen, Teresa K. — Mon, 21 Mar 2022 08:02:50 GMT-07:00

Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors

Zachova, Katerina — Thu, 03 Feb 2022 02:12:09 GMT-08:00

Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease

Vlasschaert, Caitlyn — Wed, 23 Feb 2022 08:47:01 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 29 Apr 2022 10:00:31 GMT-07:00

Clonal Hematopoiesis and CKD Progression

Niroula, Abhishek — Wed, 06 Apr 2022 09:16:38 GMT-07:00

Correction: Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome

American Society of Nephrology — Fri, 29 Apr 2022 10:00:31 GMT-07:00

Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating Factor

Wang, Yuan Min — Wed, 06 Apr 2022 08:47:58 GMT-07:00

Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury

Lidberg, Kevin A. — Wed, 23 Feb 2022 08:47:02 GMT-08:00

Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy

Xie, Xinfang — Wed, 16 Feb 2022 08:42:15 GMT-08:00

The Subcellular Localization of RRAGD

Ma, Tiantian — Thu, 31 Mar 2022 08:29:33 GMT-07:00

More Research is Still Needed To Support The Real-world Generalizability of The Benefits of Lifestyle Interventions for CKD

Huang, Liuyan — Wed, 30 Mar 2022 08:26:10 GMT-07:00

DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants

Chun, Justin — Tue, 01 Mar 2022 07:48:04 GMT-08:00

Targeting Cathepsin C in PR3-ANCA Vasculitis

Jerke, Uwe — Tue, 15 Mar 2022 08:38:01 GMT-07:00

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Xu, Chelsea — Tue, 01 Mar 2022 07:48:04 GMT-08:00

Hematopoietic Stem Cell Transplant-Membranous Nephropathy Is Associated with Protocadherin FAT1

Sethi, Sanjeev — Wed, 23 Mar 2022 10:18:24 GMT-07:00

Further Evidence for the Mucosal Origin of Pathogenic IgA in IgA Nephropathy

Cheung, Chee Kay — Thu, 07 Apr 2022 08:25:23 GMT-07:00

A View on Cathepsin C as a Target for Therapy in AAV

Kain, Renate — Fri, 08 Apr 2022 07:49:33 GMT-07:00

SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis Patients

Shankar, Sushma — Thu, 31 Mar 2022 07:50:52 GMT-07:00

Dissipating the Fog at the Crossroad: Predicting Survival after the Initiation of Kidney Replacement Therapy

Côté, Jean-Maxime — Thu, 28 Apr 2022 06:00:32 GMT-07:00

AKI in a Patient with Urinary Tract Infection, Urinary Crystals, and a Bladder Stone

Schretlen, Claire F. — Thu, 28 Apr 2022 06:00:32 GMT-07:00

The Implementation of a Virtual Home Dialysis Mentoring Program for Nephrologists

Abra, Graham — Wed, 26 Jan 2022 01:33:56 GMT-08:00

Mind the Cast: FENa versus Microscopy in AKI

Hoenig, Melanie P. — Thu, 28 Apr 2022 06:00:32 GMT-07:00

Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor UBE-1099 Ameliorates Progressive Phenotype in Alport Syndrome Mouse Model

Kaseda, Shota — Fri, 03 Dec 2021 08:09:40 GMT-08:00

Modifiable Lifestyle Behaviors and CKD Progression: A Narrative Review

Schrauben, Sarah J. — Tue, 18 Jan 2022 06:23:56 GMT-08:00

Living a healthy lifestyle is one of the safest and most cost-effective ways to improve one’s quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non–dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.

Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: PRO

Cavanaugh, Corey — Fri, 10 Sep 2021 06:41:11 GMT-07:00

Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros

Nishimura, Yusuke — Wed, 19 Jan 2022 11:33:25 GMT-08:00

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease

Saraf, Santosh L. — Thu, 03 Feb 2022 11:47:22 GMT-08:00

Mission and 1-Year Outcomes of a Cardiorenal Subspecialty Consultation Service

Bansal, Nisha — Wed, 26 Jan 2022 09:42:05 GMT-08:00

Delayed Graft Function Complicated by Anuria in a Kidney Transplant Patient

Etta, Praveen Kumar — Thu, 28 Apr 2022 06:00:32 GMT-07:00

Association of Monocyte Count and Monocyte/Lymphocyte Ratio with the Risk of Cardiovascular Outcomes in Patients with CKD

Oh, Ester S. — Thu, 03 Feb 2022 01:57:02 GMT-08:00

A Novel Predictive Model for Hospital Survival in Patients who are Critically Ill with Dialysis-Dependent AKI: A Retrospective Single-Center Exploratory Study

Ganguli, Anirban — Tue, 25 Jan 2022 05:38:45 GMT-08:00

Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation Failure

Martinez, Laisel — Fri, 14 Jan 2022 09:46:31 GMT-08:00

Association of Contrast-Enhanced Ultrasound–Derived Kidney Cortical Microvascular Perfusion with Kidney Function

Srivastava, Anand — Wed, 26 Jan 2022 01:33:56 GMT-08:00

Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI

Varghese, Vipin — Wed, 19 Jan 2022 01:30:01 GMT-08:00

Challenges of Conducting Clinical Trials during the SARS-CoV-2 Pandemic: The ASCEND Global Program Experience

Johansen, Kirsten L. — Thu, 10 Feb 2022 01:27:49 GMT-08:00

Global Perspectives in Acute Kidney Injury: Mexico

Chávez-Íñiguez, Jonathan S. — Tue, 25 Jan 2022 09:34:10 GMT-08:00

The Role of Peritoneal Dialysis in Different Phases of Kidney Transplantation

Gardezi, Ali I. — Mon, 28 Feb 2022 06:11:13 GMT-08:00

The utilization of peritoneal dialysis (PD) has been increasing in the past decade owing to various government initiatives and recognition of benefits such as better preservation of residual renal function, quality of life, and lower cost. The Advancing American Kidney Health initiative aims to increase the utilization of home therapies such as PD and kidney transplantation to treat end stage kidney disease (ESKD). A natural consequence of this development is that more patients will receive PD, and many will eventually undergo kidney transplantation. Therefore, it is important to understand the effect of pretransplant PD on posttransplant outcomes such as delayed graft function (DGF), rejection, thrombosis, graft, and patient survival. Furthermore, some of these patients may develop DGF, which raises the question of the utility of PD during DGF and its risks. Although transplant is the best renal replacement therapy option, it is not everlasting, and many transplant recipients must go on dialysis after allograft failure. Can PD be a good option for these patients? This is another critical question. Furthermore, a significant proportion of nonrenal solid organ transplant recipients develop ESKD. Is PD feasible in this group? In this review, we try to address all of these questions in the light of available evidence.

Predictors of Hyperkalemia among Patients on Maintenance Hemodialysis Transported to the Emergency Department by Ambulance

Vinson, Amanda J. — Wed, 09 Feb 2022 10:18:39 GMT-08:00

Clinical Events and Renal Function in the First Year Predict Long-Term Kidney Transplant Survival

Schold, Jesse D. — Tue, 25 Jan 2022 05:38:45 GMT-08:00

Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: CON

La, Ashley — Fri, 10 Sep 2021 06:41:12 GMT-07:00

Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: COMMENTARY

Uduman, Junior — Fri, 10 Sep 2021 06:41:12 GMT-07:00

Perspective on Nonsteroidal Mineralocorticoid Receptor Antagonism in Diabetic Kidney Disease

Ghuman, Jasleen K. — Wed, 19 Jan 2022 01:30:01 GMT-08:00

Impact of Metabolic Acidosis and Alkali Therapy on Linear Growth in Children with Chronic Kidney Disease: What Is the Current Evidence?

Ulrich, Emma H. — Thu, 28 Apr 2022 06:00:32 GMT-07:00

Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD

Brown, Denver D. — Wed, 09 Feb 2022 10:18:39 GMT-08:00

A Brief Introduction to Competing Risks in the Context of Kidney Disease Epidemiology

Roetker, Nicholas S. — Thu, 17 Feb 2022 11:48:22 GMT-08:00

Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: PRO

ghaffari@usc.edu — Tue, 12 Apr 2022 01:16:11 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007822021 and the COMMENTARY: 10.34067/KID.0002342022

Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: COMMENTARY

mhr9r@virginia.edu — Tue, 12 Apr 2022 01:16:11 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the CON: 10.34067/KID.0007822021

Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: CON

randy.luciano@yale.edu — Tue, 12 Apr 2022 01:16:11 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the COMMENTARY: 10.34067/KID.0002342022

Is There an Ideal Recipe to Increase Home Dialysis Use?

Shen, Jenny I. — Mon, 21 Mar 2022 11:23:06 GMT-07:00

Measuring Disease and Transplant Knowledge among Patients with Advanced CKD

Urbanski, Megan A. — Thu, 24 Mar 2022 07:14:57 GMT-07:00

Symptoms with or because of Kidney Failure?

Abdel-Kader, Khaled — Fri, 04 Mar 2022 10:13:51 GMT-08:00

Could Phosphate Provide a Second Chance for Statin Therapy in Kidney Failure?

Gutiérrez, Orlando M. — Wed, 02 Mar 2022 09:43:50 GMT-08:00

Syndromes of Pseudo-Hyperaldosteronism

Rizzolo, Katherine — Tue, 08 Feb 2022 07:59:53 GMT-08:00

Pattern Recognition versus Pathogenesis

Hoenig, Melanie P. — Thu, 03 Mar 2022 05:05:39 GMT-08:00

Correction: Prevention of Bloodstream Infections in Patients Undergoing Hemodialysis

American Society of Nephrology — Fri, 04 Mar 2022 09:45:00 GMT-08:00

Variations in Deceased Donor Terminal Creatinine Values Reported in the OPTN Data Registry

Yu, Kathleen — Wed, 23 Feb 2022 08:47:22 GMT-08:00

Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD

Kramers, Bart J. — Mon, 21 Mar 2022 10:25:27 GMT-07:00

Introduction to Critical Care Nephrology and Acute Kidney Injury

Liu, Kathleen D. — Thu, 10 Mar 2022 07:00:01 GMT-08:00

The Knowledge Assessment of Renal Transplantation (KART) 2.0

Waterman, Amy D. — Thu, 24 Mar 2022 07:14:57 GMT-07:00

Kidney Histopathologic Spectrum and Clinical Indicators Associated with MGRS

Yong, Zi-hao — Thu, 24 Feb 2022 06:00:46 GMT-08:00

Knowledge Measurement Can Point to Opportunities, but Has Limits

Franks, Karol A. — Thu, 24 Mar 2022 07:14:56 GMT-07:00

Association of Serum Phosphate with Efficacy of Statin Therapy in Hemodialysis Patients

Massy, Ziad A. — Wed, 02 Mar 2022 09:43:50 GMT-08:00

Management of Respiratory Failure

Pearson, Steven D. — Thu, 10 Mar 2022 07:00:01 GMT-08:00

Mechanical ventilation is a lifesaving therapy for critically ill patients with respiratory failure, but like all treatments, it has the potential to cause harm if not administered appropriately. This review aims to give an overview of the basic principles of invasive and noninvasive mechanical ventilation. Topics covered include modes of mechanical ventilation, respiratory mechanics and ventilator waveform interpretation, strategies for initial ventilator settings, indications and contraindications for noninvasive ventilation, and the effect of the ventilator on kidney function.

Multifaceted Intervention to Increase the Use of Home Dialysis

Manns, Braden J. — Mon, 21 Mar 2022 11:07:36 GMT-07:00

Trajectories of Uremic Symptom Severity and Kidney Function in Patients with Chronic Kidney Disease

Wulczyn, Kendra E. — Fri, 04 Mar 2022 10:26:00 GMT-08:00

Breaking the Barriers to Innovation in Kidney Care

Nissenson, Allen R. — Tue, 15 Feb 2022 07:19:38 GMT-08:00

Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug Use

Stalund, Ida V. — Wed, 16 Mar 2022 08:35:00 GMT-07:00

Patient-Reported Symptoms and Subsequent Risk of Myocardial Infarction in Chronic Kidney Disease

Lidgard, Benjamin — Thu, 17 Mar 2022 07:42:34 GMT-07:00

Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney Disease

Patel, Jiten — Wed, 15 Dec 2021 10:07:40 GMT-08:00

The Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. Herein, we describe the case of a 66-year-old woman with CKD who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient’s histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease. Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures that were uncovered revealed evidence of early diabetic kidney disease adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of diabetic kidney disease was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.

In Defense of Normal Saline

Mikhael, Bassem — Wed, 09 Feb 2022 08:21:01 GMT-08:00

Extracorporeal Treatment for Methotrexate Poisoning

Ghannoum, Marc — Wed, 02 Mar 2022 09:43:50 GMT-08:00

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada

Oliver, Matthew J. — Wed, 09 Mar 2022 07:40:59 GMT-08:00

Endocytosis Begins inside the Cell

Beenken, Andrew — Mon, 07 Mar 2022 07:48:29 GMT-08:00

Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector–Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients

Brunelli, Steven M. — Tue, 08 Feb 2022 08:27:07 GMT-08:00

A Founder Mutation in EHD1 Presents with Tubular Proteinuria and Deafness

Issler, Naomi — Fri, 11 Feb 2022 07:10:15 GMT-08:00

Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease

Verissimo, Thomas — Thu, 10 Mar 2022 07:04:49 GMT-08:00

The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland

Bell, Samira — Wed, 02 Feb 2022 09:35:54 GMT-08:00

Authors’ Reply: Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells

Sato, Yuki — Thu, 03 Feb 2022 09:51:58 GMT-08:00

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells

du Long, Romy — Thu, 03 Feb 2022 10:21:39 GMT-08:00

Correction: Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity

American Society of Nephrology — Thu, 31 Mar 2022 10:00:34 GMT-07:00

New Insights into the Pivotal Roles of Claudins in Proximal Tubule Electrolyte Reabsorption

Aronson, Peter S. — Wed, 09 Mar 2022 08:33:17 GMT-08:00

Lipopolysaccharide Pretreatment Prevents Medullary Vascular Congestion following Renal Ischemia by Limiting Early Reperfusion of the Medullary Circulation

McLarnon, Sarah R. — Thu, 03 Feb 2022 02:12:09 GMT-08:00

The Search for the Perfect Agent for Anemia Management in Chronic Kidney Disease

Locatelli, Francesco — Thu, 31 Mar 2022 10:00:34 GMT-07:00

Authors’ Reply: SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?

Schrezenmeier, Eva — Mon, 14 Feb 2022 09:17:25 GMT-08:00

Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study

Uhlin, Fredrik — Tue, 08 Mar 2022 07:47:25 GMT-08:00

α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier

Rogg, Manuel — Tue, 08 Mar 2022 07:47:24 GMT-08:00

Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study

Fishbane, Steven — Thu, 31 Mar 2022 10:00:34 GMT-07:00

Premature Death in Kidney Transplant Recipients: The Time for Trials is Now

Vinson, Amanda J. — Tue, 15 Mar 2022 08:38:02 GMT-07:00

Claudin-10a Deficiency Shifts Proximal Tubular Cl- Permeability to Cation Selectivity via Claudin-2 Redistribution

Breiderhoff, Tilman — Fri, 14 Jan 2022 08:48:18 GMT-08:00

A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport Syndrome

Widjaja, Anissa A. — Wed, 09 Feb 2022 11:23:10 GMT-08:00

SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?

Wijtvliet, Veerle — Mon, 14 Feb 2022 10:29:21 GMT-08:00

The Non-Inferiority Complex: What Do Non-Inferiority Trials Tell Us?

Assimon, Magdalene M. — Thu, 31 Mar 2022 10:00:34 GMT-07:00

This Month's Highlights

American Society of Nephrology — Thu, 31 Mar 2022 10:00:34 GMT-07:00

A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in Mice

Song, Cheng J. — Wed, 02 Feb 2022 09:35:54 GMT-08:00

How Whole Slide Imaging and Machine Learning Can Partner with Renal Pathology

Wilson, Parker C. — Thu, 31 Mar 2022 06:30:32 GMT-07:00

Is There a Role for More Intense Immunosuppression in IgA Nephropathy?

Aron, Abraham W. — Thu, 31 Mar 2022 06:30:32 GMT-07:00

Explainable Biomarkers for Automated Glomerular and Patient-Level Disease Classification

Basso, Matthew Nicholas — Thu, 09 Dec 2021 07:34:46 GMT-08:00

Pathologists use multiple microscopy modalities to assess renal biopsy specimens. Besides usual diagnostic features, some changes are too subtle to be properly defined. Computational approaches have the potential to systematically quantitate subvisual clues, provide pathogenetic insight, and link to clinical outcomes. To this end, a proof-of-principle study is presented demonstrating that explainable biomarkers through machine learning can distinguish between glomerular disorders at the light-microscopy level. The proposed system used image analysis techniques and extracted 233 explainable biomarkers related to color, morphology, and microstructural texture. Traditional machine learning was then used to classify minimal change disease (MCD), membranous nephropathy (MN), and thin basement membrane nephropathy (TBMN) diseases on a glomerular and patient-level basis. The final model combined the Gini feature importance set and linear discriminant analysis classifier. Six morphologic (nuclei-to-glomerular tuft area, nuclei-to-glomerular area, glomerular tuft thickness greater than ten, glomerular tuft thickness greater than three, total glomerular tuft thickness, and glomerular circularity) and four microstructural texture features (luminal contrast using wavelets, nuclei energy using wavelets, nuclei variance using color vector LBP, and glomerular correlation using GLCM) were, together, the best performing biomarkers. Accuracies of 77% and 87% were obtained for glomerular and patient-level classification, respectively. Computational methods, using explainable glomerular biomarkers, have diagnostic value and are compatible with our existing knowledge of disease pathogenesis. Furthermore, this algorithm can be applied to clinical datasets for novel prognostic and mechanistic biomarker discovery.

How the University of Washington Implemented a Change in eGFR Reporting

Nkinsi, Naomi T. — Wed, 26 Jan 2022 09:42:05 GMT-08:00

Extrarenal Effects of Aldosterone on Potassium Homeostasis

Palmer, Biff F. — Fri, 14 Jan 2022 01:30:12 GMT-08:00

The role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in nontransporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.

Nephrology Considerations in the Management of Durable and Temporary Mechanical Circulatory Support

Walther, Carl P. — Fri, 14 Jan 2022 01:30:12 GMT-08:00

Durable and temporary mechanical circulatory support (MCS) use is growing for a range of cardiovascular indications. Kidney dysfunction is common in people evaluated for or receiving durable or temporary MCS and portends worse outcomes. This kidney dysfunction can be due to preexisting kidney chronic kidney disease (CKD), acute kidney injury (AKI) related to acute cardiovascular disease necessitating MCS, AKI due to cardiac procedures, and acute and chronic MCS effects and complications. Durable MCS, with implantable continuous flow pumps, is used for long-term support in advanced heart failure refractory to guideline-directed medical and device therapy, either permanently or as a bridge to heart transplantation. Temporary MCS—encompassing in this review intra-aortic balloon pumps (IABP), axial flow pumps, centrifugal flow pumps, and venoarterial ECMO—is used for diverse situations: high-risk percutaneous coronary interventions (PCI), acute decompensated heart failure, cardiogenic shock, and resuscitation after cardiac arrest. The wide adoption of MCS makes it imperative to improve understanding of the effects of MCS on kidney health/function and of kidney health/function on MCS outcomes. The complex structure and functions of the kidney, and the complex health states of individuals receiving MCS, makes investigations in this area challenging, and current knowledge is limited. Fortunately, the increasing nephrology toolbox of noninvasive kidney health/function assessments may enable development and testing of individualized management strategies and therapeutics in the future. We review technology, epidemiology, pathophysiology, clinical considerations, and future directions in MCS and nephrology.

Kidney Injury in Patients Treated with Immune Checkpoint Inhibitors Does Not Meet KDIGO-AKI Criteria

Verploegen, Maartje F.A. — Tue, 21 Dec 2021 11:52:25 GMT-08:00

Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: PRO

Chung, Kevin K. — Thu, 19 Aug 2021 01:30:39 GMT-07:00

The Role of Kidney Biopsy in Immune Checkpoint Inhibitor-Associated AKI

Rashidi, Arash — Thu, 13 Jan 2022 10:48:21 GMT-08:00

Dark Urine in a Dialysis Patient Treated for a Bloodstream Infection

Kento, Furuya — Thu, 31 Mar 2022 06:30:32 GMT-07:00

Trends in Coronary Artery Disease Screening before Kidney Transplantation

Cheng, Xingxing S. — Thu, 09 Dec 2021 09:46:05 GMT-08:00

Feeding the Kidney Researcher Pipeline through R25-NIDDK Funded Summer Undergraduate Research Fellowships: A Student Perspective

Wilson, Elena M. — Fri, 22 Oct 2021 07:36:31 GMT-07:00

Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: CON

Kashani, Kianoush — Thu, 19 Aug 2021 01:30:39 GMT-07:00

Artificial Intelligence in the Identification, Management, and Follow-Up of CKD

Tangri, Navdeep — Tue, 18 Jan 2022 06:23:56 GMT-08:00

Effect of Cyclophosphamide and Glucocorticoid Therapy in IgA Nephropathy: A Single-Center Retrospective Analysis

Beck, Nicolas — Wed, 19 Jan 2022 11:33:25 GMT-08:00

Urinary Podocyte Biomarkers and Glomerular Histologic Change

Inoue, Kazunori — Thu, 31 Mar 2022 06:30:32 GMT-07:00

CKD Biomarkers, Cognitive Impairment, and Incident Dementia in an Older Healthy Cohort

Murray, Anne M. — Tue, 07 Dec 2021 11:30:16 GMT-08:00

Patient-Reported Experiences after Acute Kidney Injury across Multiple Health-Related Quality-of-Life Domains

Switzer, Galen E. — Wed, 08 Dec 2021 02:00:13 GMT-08:00

Initial Home Dialysis Is Increased for Rural Patients by Accessing Urban Facilities

Adler, Joel T. — Tue, 04 Jan 2022 05:02:17 GMT-08:00

Unexpected Kidney Finding in a Patient with Anemia

Uzu, Takashi — Thu, 31 Mar 2022 06:30:32 GMT-07:00

Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: COMMENTARY

Ostermann, Marlies — Thu, 19 Aug 2021 01:30:39 GMT-07:00

Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD: A Cross-Sectional Registry Analysis

Zhuo, Min — Wed, 19 Jan 2022 01:30:01 GMT-08:00

Drug-Induced Osmotic Nephropathy: Add SGLT2-Inhibitors to the List?

Perazella, Mark A. — Tue, 21 Dec 2021 01:32:50 GMT-08:00

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials

Zhang, Jingjing — Wed, 19 Jan 2022 11:33:25 GMT-08:00

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease

Jones, Brian E. — Wed, 08 Dec 2021 05:27:57 GMT-08:00

Three-Dimensional Super-Resolved Imaging of Paraffin-Embedded Kidney Samples

Unnersjö-Jess, David — Fri, 03 Dec 2021 08:09:40 GMT-08:00

Evaluation of Suspected Autosomal Alport Syndrome Synonymous Variants

Rossanti, Rini — Thu, 14 Oct 2021 09:25:28 GMT-07:00

Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: COMMENTARY

atolwani@uabmc.edu — Fri, 25 Mar 2022 01:37:16 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the CON: 10.34067/KID.0000092022

Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: CON

bagshaw@ualberta.ca — Fri, 25 Mar 2022 01:37:16 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the COMMENTARY: 10.34067/KID.0002002022

Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: PRO

palevsky@pitt.edu — Fri, 25 Mar 2022 01:37:16 GMT-07:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0000092022 and the COMMENTARY: 10.34067/KID.0002002022

Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: PRO

Adnan.Sharif@uhb.nhs.uk — Tue, 08 Mar 2022 01:04:13 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007162021 and the COMMENTARY: 10.34067/KID.0001692022

Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: CON

jiun-ruey.hu@yale.edu — Tue, 08 Mar 2022 01:04:13 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the COMMENTARY: 10.34067/KID.0001692022

Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: COMMENTARY

hart1044@umn.edu — Tue, 08 Mar 2022 01:04:13 GMT-08:00

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the CON: 10.34067/KID.0007162021

How I Treat Complement-Mediated TMA

Sperati, C. John — Mon, 24 Jan 2022 08:05:29 GMT-08:00

Will New Treatment Options for Lupus Nephritis Be Affordable?

Teng, Y.K. Onno — Fri, 04 Feb 2022 11:09:02 GMT-08:00

Can Novel Potassium Binders Liberate People with Chronic Kidney Disease from the Low-Potassium Diet?

St-Jules, David E. — Wed, 20 Oct 2021 07:26:37 GMT-07:00

The advent of new potassium binders provides an important breakthrough in the chronic management of hyperkalemia for people with CKD. In addition to the direct benefits of managing hyperkalemia, many researchers and clinicians view these new medications as a possible means to safely transition patients away from the low-potassium diet to a more healthful eating pattern. In this review, we examine the mechanisms of potassium binders in the context of hyperkalemia risk related to dietary potassium intake in people with CKD. We note that whereas these medications target hyperkalemia caused by potassium bioaccumulation, the primary evidence for restricting dietary potassium is risk of postprandial hyperkalemia. The majority of ingested potassium is absorbed alongside endogenously secreted potassium in the small intestines, but the action of these novel medications is predominantly constrained to the large intestine. As a result and despite their effectiveness in lowering basal potassium levels, it remains unclear whether potassium binders would provide protection against hyperkalemia caused by excessive dietary potassium intake in people with CKD. Until this knowledge gap is bridged, clinicians should consider postprandial hyperkalemia risk when removing restrictions on dietary potassium intake in people with CKD on potassium binders.

Functional Reserve of the Kidney

Armenta, Armando — Wed, 10 Nov 2021 09:47:59 GMT-08:00

An exploration of the normal limits of physiologic responses and how these responses are lost when the kidney is injured rarely occurs in clinical practice. However, the differences between “resting” and “stressed” responses identify an adaptive reactiveness that is diminished before baseline function is impaired. This functional reserve is important in the evaluation of prognosis and progression of kidney disease. Here, we discuss stress tests that examine protein-induced hyperfiltration, proximal tubular secretion, urea-selective concentration defects, and acid retention. We discuss diseases in which these tests have been used to diagnose subclinical injury. The study and follow-up of abnormal functional reserve may add considerable understanding to the natural history of CKD.

Hyperkalemia with Mineralocorticoid Receptor Antagonist Use in People with CKD

Epstein, Murray — Wed, 01 Dec 2021 10:38:50 GMT-08:00

Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial

Charytan, David M. — Fri, 21 Jan 2022 01:53:52 GMT-08:00

Comparison of Aptamer-Based and Antibody-Based Assays for Protein Quantification in Chronic Kidney Disease

Lopez-Silva, Carolina — Wed, 23 Feb 2022 06:47:04 GMT-08:00

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States

Mandrik, Olena — Thu, 03 Feb 2022 02:12:26 GMT-08:00

Volume Progression and Imaging Classification of Polycystic Liver in Early Autosomal Dominant Polycystic Kidney Disease

Bae, Kyongtae T. — Fri, 25 Feb 2022 07:38:43 GMT-08:00

Inflammatory Cells in Nephrectomy Tissue from Patients without and with a History of Urinary Stone Disease

Dejban, Pegah — Tue, 25 Jan 2022 09:43:06 GMT-08:00

Effect of the Refitted Race-Free eGFR Formula on the CKD Prevalence and Mortality in the Danish Population

Vestergaard, Søren Viborg — Tue, 11 Jan 2022 09:40:48 GMT-08:00

Exploring the Role of Inflammation toward the Pathogenesis of Calcium Nephrolithiasis

Sakhaee, Khashayar — Tue, 25 Jan 2022 09:43:06 GMT-08:00

De Novo Malignancies after Kidney Transplantation

Al-Adra, David — Mon, 29 Mar 2021 10:58:19 GMT-07:00

Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.

Managing Patients with Failing Kidney Allograft

Davis, Scott — Wed, 10 Mar 2021 08:40:38 GMT-08:00

Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.

Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 Surge

Scherer, Jennifer S. — Thu, 24 Feb 2022 06:51:23 GMT-08:00

Growing Understanding of the Clinical and Serologic Effects of COVID-19 Vaccines in Patients Undergoing Long-Term Dialysis

Hundemer, Gregory L. — Thu, 10 Feb 2022 07:07:48 GMT-08:00

Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months

Hsu, Caroline M. — Thu, 10 Feb 2022 07:07:49 GMT-08:00

Vaccination and COVID-19 Dynamics in Dialysis Patients

El Karoui, Khalil — Thu, 10 Feb 2022 07:07:48 GMT-08:00

Renin-Angiotensin-Aldosterone System Inhibitors and the Risk of AKI in COVID-19 Compared with Influenza

Birkelo, Bethany C. — Wed, 02 Feb 2022 06:42:04 GMT-08:00

Catheter-Associated Bloodstream Infections among Patients on Hemodialysis

Johansen, Kirsten L. — Wed, 02 Feb 2022 06:42:04 GMT-08:00

Measures implemented to prevent transmission of severe acute respiratory syndrome coronavirus 2 in outpatient dialysis facilities may also help to prevent catheter-associated bloodstream infections in patients receiving hemodialysis. We used United States Renal Data System data to examine rates of antibiotic administration within dialysis facilities and rates of hospital admission for catheter-associated bloodstream infection from March 2018 through November 2020, and rates of hospitalization for sepsis, to address overall changes in hospitalization during the coronavirus disease 2019 (COVID-19) pandemic. Using logistic regression, we estimated year-over-year adjusted odds ratios of these events in 3-month intervals. During the first 6 months of the pandemic, rates of antibiotic administration were between 20% and 21% lower, and rates of hospitalization for catheter-associated bloodstream infection were between 17% and 24% lower than during corresponding periods in 2019, without significant changes in rates of hospitalization for sepsis. However, rates of catheter-associated events also decreased between 2018 and 2019, driven by reductions in facilities operated by a large dialysis provider. These data suggest that significant reductions in catheter-associated infections occurred during the pandemic, superimposed on nonpandemic-related reductions in some facilities before the pandemic. Even after the pandemic, it may be prudent to continue some COVID-19 mitigation measures to prevent catheter-associated bloodstream infections.

COVID-19 and Palliative Care

Hickey, Edward V. — Thu, 24 Feb 2022 07:07:11 GMT-08:00

Extracellular Vesicles as Novel Players in Kidney Disease

Blijdorp, Charles J. — Mon, 07 Feb 2022 07:20:55 GMT-08:00

This Month's Highlights

American Society of Nephrology — Mon, 28 Feb 2022 10:00:24 GMT-08:00

Risk Prediction Models for Atherosclerotic Cardiovascular Disease in Patients with Chronic Kidney Disease: The CRIC Study

Bundy, Joshua D. — Thu, 10 Feb 2022 07:47:36 GMT-08:00

Urine Uromodulin and Genetics of its Variation

Franceschini, Nora — Mon, 28 Feb 2022 10:00:24 GMT-08:00

Natural History of Bone Disease following Kidney Transplantation

Jørgensen, Hanne Skou — Wed, 19 Jan 2022 11:58:37 GMT-08:00

Autoimmune Podocytopathies: A Novel Sub-Group of Diseases from Childhood Idiopathic Nephrotic Syndrome

Ye, Qing — Fri, 21 Jan 2022 06:07:08 GMT-08:00

Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells

Liu, Jialing — Fri, 28 Jan 2022 10:45:04 GMT-08:00

Cardiovascular Risk Prediction Scores in CKD: What Are We Missing?

Soomro, Qandeel H. — Thu, 10 Feb 2022 07:23:01 GMT-08:00

Authors’ Reply

Guedes, Murilo — Wed, 19 Jan 2022 08:51:42 GMT-08:00

Plasma Exchange in ANCA-Associated Vasculitis: For Whom (If Any)?

Walsh, Michael — Mon, 24 Jan 2022 11:41:24 GMT-08:00

Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury

Mansour, Sherry G. — Tue, 11 Jan 2022 09:52:07 GMT-08:00

Tissue Culture Models of AKI: From Tubule Cells to Human Kidney Organoids

Bejoy, Julie — Fri, 14 Jan 2022 08:48:18 GMT-08:00

AKI affects approximately 13.3 million people around the world each year, causing CKD and/or mortality. The mammalian kidney cannot generate new nephrons after postnatal renal damage and regenerative therapies for AKI are not available. Human kidney tissue culture systems can complement animal models of AKI and/or address some of their limitations. Donor-derived somatic cells, such as renal tubule epithelial cells or cell lines (RPTEC/hTERT, ciPTEC, HK-2, Nki-2, and CIHP-1), have been used for decades to permit drug toxicity screening and studies into potential AKI mechanisms. However, tubule cell lines do not fully recapitulate tubular epithelial cell properties in situ when grown under classic tissue culture conditions. Improving tissue culture models of AKI would increase our understanding of the mechanisms, leading to new therapeutics. Human pluripotent stem cells (hPSCs) can be differentiated into kidney organoids and various renal cell types. Injury to human kidney organoids results in renal cell-type crosstalk and upregulation of kidney injury biomarkers that are difficult to induce in primary tubule cell cultures. However, current protocols produce kidney organoids that are not mature and contain off-target cell types. Promising bioengineering techniques, such as bioprinting and “kidney-on-a-chip” methods, as applied to kidney nephrotoxicity modeling advantages and limitations are discussed. This review explores the mechanisms and detection of AKI in tissue culture, with an emphasis on bioengineered approaches such as human kidney organoid models.

Mechanisms and Models of Kidney Tubular Necrosis and Nephron Loss

Maremonti, Francesca — Wed, 12 Jan 2022 09:56:46 GMT-08:00

Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this “switch” must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.

Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients

Rostoker, Guy — Wed, 19 Jan 2022 09:24:20 GMT-08:00

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges

Nezam, Dorian — Mon, 24 Jan 2022 12:05:46 GMT-08:00

Correction: Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKI

American Society of Nephrology — Mon, 28 Feb 2022 10:00:24 GMT-08:00

Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice

Maeoka, Yujiro — Fri, 21 Jan 2022 09:41:50 GMT-08:00

Authors’ Reply

Watts, Andrew J.B. — Fri, 21 Jan 2022 05:36:13 GMT-08:00

Vitamin C Deficiency Causes Cell Type–Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse Model

Yu, Zihui — Tue, 04 Jan 2022 09:36:13 GMT-08:00

Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathway

van Megen, Wouter H. — Wed, 12 Jan 2022 09:56:46 GMT-08:00

Recurrence of Anti-Semaphorin 3B–Mediated Membranous Nephropathy after Kidney Transplantation

Fila, Marc — Tue, 11 Jan 2022 09:52:07 GMT-08:00

Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin

Joseph, Christina B. — Mon, 28 Feb 2022 10:00:24 GMT-08:00

Modelling and Prevention of Acute Kidney Injury through Ischemia and Reperfusion in a Combined Human Renal Proximal Tubule/Blood Vessel-on-a-Chip

Vormann, Marianne K. — Thu, 04 Nov 2021 09:28:39 GMT-07:00

Practice What you Preach: The Kidney Diet Challenge

Perez, Luis M. — Thu, 24 Feb 2022 06:30:37 GMT-08:00

Short- and Long-Term Recovery after Moderate/Severe AKI in Patients with and without COVID-19

Farrukh.Koraishy@stonybrookmedicine.edu — Mon, 29 Nov 2021 01:32:55 GMT-08:00

Fever, Dysuria, and AKI in a Kidney Transplant Patient

Akcasu, Ege — Thu, 24 Feb 2022 06:30:37 GMT-08:00

Collateral Effects and Mortality of Kidney Transplant Recipients during the COVID-19 Pandemic

Schmidt-Lauber, Christian — Thu, 18 Nov 2021 09:22:57 GMT-08:00

COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry

Waldman, Meryl — Fri, 03 Dec 2021 01:28:10 GMT-08:00

Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

Wang, Ann A. — Thu, 18 Nov 2021 01:33:14 GMT-08:00

Left Atrial Appendage Closure: An Alternative to Anticoagulation for Stroke Prevention in Patients with Kidney Disease

srivallurupalli@gmail.com — Wed, 08 Dec 2021 01:27:25 GMT-08:00

Anticoagulation to reduce thromboembolic stroke risk due to nonvalvular atrial fibrillation in ESKD is associated with increased bleeding. There is an existing debate in ESKD centers around the pros and cons of anticoagulation. We propose percutaneous left atrial appendage occlusion as a third alternative to balance thrombosis and bleeding risks in this high-risk population.

Defining Baseline Creatinine for Identification of AKI in Population-Based Laboratory Databases: A Danish Nationwide Cohort Study

Graversen, Henriette V. — Mon, 15 Nov 2021 11:52:37 GMT-08:00

Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study

Eadon, Michael T. — Thu, 09 Dec 2021 06:12:34 GMT-08:00

Hypertension Pharmacogenomics in CKD: The Clinical Relevance and Public Health Implications

Geng, Ting-Ting — Thu, 24 Feb 2022 06:30:37 GMT-08:00

Functional Drug Screening using Kidney Cells On-A-Chip: Advances in Disease Modeling and Development of Biomarkers

Ajay, Amrendra K. — Thu, 24 Feb 2022 06:30:37 GMT-08:00

The Kidney Diet Challenge: An Experiential Educational Experience

Norouzi, Sayna — Tue, 30 Nov 2021 06:13:18 GMT-08:00

Vascular Suitability for an Endovascular Arteriovenous Fistula: Getting Beyond the Velvet Rope

Wasse, Haimanot — Thu, 24 Feb 2022 06:30:37 GMT-08:00

Feasibility of Creation of an Endovascular Arteriovenous Fistula in Patients Undergoing Preoperative Vascular Mapping

Al-Balas, Alian — Wed, 20 Oct 2021 11:46:20 GMT-07:00

Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic Therapy

Velez, Juan Carlos Q. — Fri, 03 Dec 2021 01:28:10 GMT-08:00

Hepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.

The Relationship of Kidney Tubule Biomarkers with Brain Imaging in CKD Patients in SPRINT

Lmmiller@health.ucsd.edu — Wed, 08 Dec 2021 09:27:44 GMT-08:00

Severe AKI in a Patient on Multiple Antimicrobial Agents for Leg Infection

Rehan, Anam — Thu, 24 Feb 2022 06:30:37 GMT-08:00

Artificial Intelligence for AKI!Now: Let’s Not Await Plato’s Utopian Republic

Soranno, Danielle E. — Thu, 18 Nov 2021 01:33:14 GMT-08:00

Vancomycin-Associated Cast Nephropathy: Reality or Fantasy?

Stokes, Michael B. — Fri, 03 Dec 2021 08:09:40 GMT-08:00

Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the Rat

Hamlin, Diane M. — Tue, 07 Dec 2021 11:30:16 GMT-08:00

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation, including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney, were performed. Before biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed, including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function, SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50- and 100- mg/kg dose levels in the four- and ten-dose treatment groups compared with controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with microalbumin being most responsive and osteopontin least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA compared with other excretory renal function markers in a rat gentamicin acute toxicity model. In this study, serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

Association of Urine Findings with Metabolic Syndrome Traits in a Population of Patients with Nephrolithiasis

Hood, Virginia L. — Tue, 30 Nov 2021 11:37:53 GMT-08:00

Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKD

Lin, Tzu-Ling — Tue, 21 Dec 2021 09:31:25 GMT-08:00

Stages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1–5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1–2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3–5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; P<0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3–5 CKD.

A Propensity Score–Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease

Seethapathy, Rituvanthikaa — Fri, 03 Dec 2021 01:28:10 GMT-08:00

Global Perspective on Kidney Transplantation: China

Zhang, Zijian — Mon, 15 Nov 2021 11:52:37 GMT-08:00

Global Perspective on Kidney Transplantation: Argentina

Maldonado, Rafael Alberto — Fri, 10 Sep 2021 01:26:01 GMT-07:00

Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: CON

Kshirsagar, Abhijit V. — Fri, 06 Aug 2021 01:32:05 GMT-07:00

Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: COMMENTARY

Liu, Frank — Fri, 06 Aug 2021 01:32:05 GMT-07:00

Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: PRO

Coyne, Daniel W. — Fri, 06 Aug 2021 01:32:05 GMT-07:00

What Patients Teach Us About Patient Engagement in Research

Dember, Laura M. — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure

Emmens, Johanna E. — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Effects of the 2021 CKD-EPI Creatinine eGFR Equation among a National US Veteran Cohort

Gregg, L. Parker — Fri, 19 Nov 2021 08:38:56 GMT-08:00

Kidney Disease Prevalence in Transgender Individuals

Eckenrode, Han E. — Mon, 06 Dec 2021 08:39:14 GMT-08:00

Improved Survival after Acute Kidney Injury

Kashani, Kianoush — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Induction Therapy in Immunologically Well-Matched Recipients

Potluri, Vishnu S. — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Blood Pressure Management in the Patient with Chronic Kidney Disease

Muntner, Paul — Wed, 05 Jan 2022 10:13:41 GMT-08:00

Controlled Study of Decision-Making Algorithms for Kidney Replacement Therapy Initiation in Acute Kidney Injury

Kelly, Yvelynne P. — Wed, 15 Dec 2021 10:07:40 GMT-08:00

Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients

Evans, Rhys D.R. — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Introducing Nephrocardiology

Hatamizadeh, Parta — Fri, 10 Dec 2021 07:07:23 GMT-08:00

Advancing Patient-Centered Research: Enabling the Patient Voice to Be Heard

Fowler, Kevin John — Mon, 07 Feb 2022 10:00:33 GMT-08:00

Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease

Waijer, Simke W. — Tue, 07 Dec 2021 07:23:50 GMT-08:00

Patient and Caregiver Experiences and Attitudes about Their Involvement in Research in Chronic Kidney Disease

Gutman, Talia — Mon, 07 Feb 2022 10:00:33 GMT-08:00

In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury

Sohaney, Ryann — Mon, 07 Feb 2022 10:00:33 GMT-08:00

The Myeloid-Kidney Interface in Health and Disease

Vlasschaert, Caitlyn — Fri, 10 Sep 2021 07:40:18 GMT-07:00

Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.

Use of Race in Kidney Research and Medicine

Mohottige, Dinushika — Wed, 17 Nov 2021 07:41:13 GMT-08:00

Black Americans and other racially and ethnically minoritized individuals are disproportionately burdened by higher morbidity and mortality from kidney disease when compared with their White peers. Yet, kidney researchers and clinicians have struggled to fully explain or rectify causes of these inequalities. Many studies have sought to identify hypothesized genetic and/or ancestral origins of biologic or behavioral deficits as singular explanations for racial and ethnic inequalities in kidney health. However, these approaches reinforce essentialist beliefs that racial groups are inherently biologically and behaviorally different. These approaches also often conflate the complex interactions of individual-level biologic differences with aggregated population-level disparities that are due to structural racism (i.e., sociopolitical policies and practices that created and perpetuate harmful health outcomes through inequities of opportunities and resources). We review foundational misconceptions about race, racism, genetics, and ancestry that shape research and clinical practice with a focus on kidney disease and related health outcomes. We also provide recommendations on how to embed key equity-enhancing concepts, terms, and principles into research, clinical practice, and medical publishing standards.

A Heartwarming Role of the Proximal Tubules

Granda, Michael L. — Mon, 07 Feb 2022 10:00:33 GMT-08:00

The Use of Serological Tests in the Care of Patients with Lupus Nephritis

Ayoub, Isabelle — Wed, 01 Dec 2021 10:38:50 GMT-08:00

Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples

Marechal, Elise — Fri, 03 Dec 2021 09:06:28 GMT-08:00

Health-Related Quality-of-Life Trajectories over Time in Older Men and Women with Advanced Chronic Kidney Disease

Chesnaye, Nicholas C. — Mon, 24 Jan 2022 08:05:28 GMT-08:00

Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD

Nowak, Kristen L. — Tue, 14 Dec 2021 08:04:44 GMT-08:00

Long-Term Infectious Complications of Kidney Transplantation

Agrawal, Akansha — Tue, 20 Apr 2021 11:01:50 GMT-07:00

Infections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care–associated infections, whereas late infections, beyond 6–12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and Clostridioides difficile colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.

Long-Term Care of the Pediatric Kidney Transplant Recipient

Fernandez, Hilda E. — Wed, 12 May 2021 07:36:09 GMT-07:00

Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD

Bansal, Nisha — Fri, 17 Dec 2021 11:42:38 GMT-08:00

Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation Study

Korfiatis, Panagiotis — Tue, 07 Dec 2021 07:24:09 GMT-08:00

Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury

Martin-Sanchez, Diego — Wed, 19 Jan 2022 09:39:06 GMT-08:00

The Trifecta Study: Comparing Plasma Levels of Donor-derived Cell-Free DNA with the Molecular Phenotype of Kidney Transplant Biopsies

Halloran, Philip F. — Thu, 20 Jan 2022 07:40:42 GMT-08:00

Cisplatin-Induced Kidney Injury: Delivering the Goods

Curry, Joshua N. — Mon, 31 Jan 2022 10:00:27 GMT-08:00

Arteritis Status and Renal Involvement in ANCA-Associated Vasculitis

Aendekerk, Joop P. — Mon, 31 Jan 2022 10:00:27 GMT-08:00

Authors’ Reply

Wetmore, James B. — Mon, 31 Jan 2022 10:00:27 GMT-08:00

This Month's Highlights

American Society of Nephrology — Mon, 31 Jan 2022 10:00:27 GMT-08:00

Confirmed Drop in Treatment of Patients with Incident End-Stage Kidney Disease During the Novel Coronavirus Disease 2019 Pandemic

Jacobs, Lucas — Mon, 31 Jan 2022 10:00:27 GMT-08:00

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Neuen, Brendon L. — Fri, 03 Dec 2021 08:58:49 GMT-08:00

Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout Mice

Hosoya, Takuji — Fri, 19 Nov 2021 08:22:41 GMT-08:00

Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and Mechanisms

Steiger, Stefanie — Tue, 14 Dec 2021 07:50:01 GMT-08:00

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.

Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical Trial

Beetham, Kassia S. — Fri, 10 Dec 2021 07:22:40 GMT-08:00

Authors’ Reply

Boudhabhay, Idris — Mon, 31 Jan 2022 10:00:27 GMT-08:00

Comparing Plasma Donor-Derived Cell-free DNA to Indication Kidney Biopsy Tissue Gene Expression: Toward Understanding the Molecular Equivalents of Non-Invasive Tests

Kurian, Sunil — Thu, 20 Jan 2022 07:24:45 GMT-08:00

Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation

Guo, Xiaojia — Fri, 17 Dec 2021 11:42:38 GMT-08:00

Spatially Resolved Transcriptomic Analysis of Acute Kidney Injury in a Female Murine Model

Dixon, Eryn E. — Wed, 01 Dec 2021 09:28:12 GMT-08:00

Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA

Viering, Daan — Mon, 04 Oct 2021 12:36:06 GMT-07:00

Using Machine Learning to Identify Metabolomic Signatures of Pediatric Chronic Kidney Disease Etiology

Lee, Arthur M. — Tue, 11 Jan 2022 09:52:05 GMT-08:00

Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome

Iijima, Kazumoto — Wed, 08 Dec 2021 01:55:07 GMT-08:00

Global Dialysis Perspective: France

Canaud, Bernard — Mon, 25 Oct 2021 07:29:09 GMT-07:00

Global Dialysis Perspective: Fiji

Talbot, Benjamin — Wed, 27 Oct 2021 05:48:31 GMT-07:00

Unusual Ultrasound Findings in a Difficult to Cannulate Arteriovenous Graft

Gossett, Christy L. — Thu, 27 Jan 2022 08:00:35 GMT-08:00

The Downside of Telephone Health Visits in a Kidney Transplant Patient during the COVID-19 Pandemic

Ross-Smith, Maree S. — Thu, 27 Jan 2022 08:00:35 GMT-08:00

Dissemination and Implementation Science: A Primer and Applications in Nephrology

Urbanski, Megan A. — Fri, 15 Oct 2021 12:51:19 GMT-07:00

Quantitative Lung Ultrasonography for the Nephrologist: Applications in Dialysis and Heart Failure

Reisinger, Nathaniel — Thu, 11 Nov 2021 09:42:47 GMT-08:00

Volume overload, and its attendant increase in acute care utilization and cardiovascular morbidity and mortality, represents a critical challenge for the practicing nephrologist. This is particularly true among patients with ESKD on HD, where predialysis volume overload and intradialytic and postdialytic hypovolemia account for almost a third of all cost for the Medicare dialysis benefit. Quantitative lung ultrasound is a tool for assessing the extent of extravascular lung water that outperforms physical exam and plain chest radiography. B-lines are vertical hyperechoic artifacts present in patients with increased extravascular lung water. B-lines have been shown to decrease dynamically during the hemodialysis treatment in proportion to ultrafiltration volume. Among patients with chronic heart failure, titration of diuretics on the basis of the extent of pulmonary congestion noted on lung ultrasonography has been shown to decrease recurrent acute care utilization. Early data from randomized controlled trials of lung ultrasound–guided ultrafiltration therapy among patients with ESKD on HD have shown promise for potential reduction in recurrent episodes of decompensated heart failure and cardiovascular events. Ultimately, lung ultrasound may predict those who are ultrafiltration tolerant and could be used to decrease acute care utilization and, thus, cost in this population.

TRPM2 Plays a Minor Role in AKI and Kidney Fibrosis

Kurata, Yu — Sat, 23 Oct 2021 06:07:33 GMT-07:00

Disparities in Discussions about Kidney Replacement Therapy in CKD Care

Barrett, Tyler M. — Sat, 23 Oct 2021 06:07:33 GMT-07:00

Obesity Related Glomerulopathy in Adolescent Women: The Effect of Body Surface Area

Bielopolski, Dana — Thu, 11 Nov 2021 01:45:22 GMT-08:00

Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19–Associated AKI

Cheung, Matthew D. — Fri, 05 Nov 2021 09:54:32 GMT-07:00

Albuminuria within the Normal Range Can Predict All-Cause Mortality and Cardiovascular Mortality

Kang, Minjung — Fri, 05 Nov 2021 02:03:36 GMT-07:00

Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKI

Li, Aihua — Wed, 03 Nov 2021 01:29:00 GMT-07:00

Bile Acids Are Important Contributors to AKI Associated with Liver Disease: CON

Allegretti, Andrew S. — Tue, 04 May 2021 02:13:17 GMT-07:00

De Novo Central Vein Stenosis in Hemodialysis Patients Following Initial Tunneled Central Vein Catheter Placement

Al-Balas, Alian — Thu, 21 Oct 2021 09:44:27 GMT-07:00

Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival

Moroni, Gabriella — Fri, 05 Nov 2021 09:54:32 GMT-07:00

Durable Protection after Anti–SARS-CoV-2 Monoclonal Antibody Therapy

Misch, Elizabeth A. — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD

Fukuda, Akihiro — Fri, 05 Nov 2021 09:54:32 GMT-07:00

Predicting Kidney Survival in Lupus Nephritis by Adding Clinical Data to Pathologic Features

Saxena, Ramesh — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Artificial Intelligence Assessment of Renal Scarring (AIRS Study)

Chantaduly, Chanon — Thu, 11 Nov 2021 01:45:21 GMT-08:00

Bile Acids Are Important Contributors to AKI Associated with Liver Disease: PRO

Fickert, Peter — Tue, 04 May 2021 02:13:17 GMT-07:00

A Second Chance at Transplant First: Preemptive Repeat Kidney Transplantation

Huml, Anne M. — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Bile Acids are Important Contributors of AKI Associated with Liver Disease: COMMENTARY

Lopez-Ruiz, Arnaldo — Tue, 04 May 2021 02:13:17 GMT-07:00

SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients

Wang, Aileen X. — Wed, 20 Oct 2021 01:24:47 GMT-07:00

Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort Study

Tennankore, Karthik K. — Fri, 22 Oct 2021 11:35:11 GMT-07:00

Kidney Disease Education Services: A Good Foundation, but More Is Needed!

Hafeez, Muhammad Saad — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Kidney Fibrosis Assessment by CT Using Machine Learning

Lemley, Kevin V. — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Disparities in Access to Preemptive Repeat Kidney Transplant: Still Missing the Mark?

Vinson, Amanda J. — Thu, 21 Oct 2021 05:56:55 GMT-07:00

A Critical Role for Shared Decision-Making about Referral and Evaluation for Kidney Transplant

Butler, Catherine R. — Thu, 27 Jan 2022 08:00:34 GMT-08:00

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury

McMahon, Kelly R. — Wed, 03 Nov 2021 01:29:00 GMT-07:00

Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis Patients

Ruchi, Rupam — Tue, 28 Sep 2021 01:12:16 GMT-07:00

Assessing Risk of Progression in ADPKD

Gordon, Craig E. — Thu, 09 Dec 2021 08:43:16 GMT-08:00

Platelet Abnormalities in CKD and Their Implications for Antiplatelet Therapy

Baaten, Constance C.F.M.J. — Mon, 08 Nov 2021 08:50:47 GMT-08:00

Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.

Temporal Trends of Dietary Risk Factors after a Diagnosis of Kidney Stones

Ferraro, Pietro Manuel — Fri, 19 Nov 2021 08:38:56 GMT-08:00

A Core Outcome Set for Trials in Glomerular Disease

Carter, Simon A. — Thu, 30 Dec 2021 09:39:23 GMT-08:00

Neutralization of SARS-CoV-2 Variants of Concern in Kidney Transplant Recipients after Standard COVID-19 Vaccination

Benning, Louise — Wed, 22 Dec 2021 11:26:04 GMT-08:00

Value-Based Care in Chronic Kidney Disease

Reaves, Allison C. — Thu, 30 Dec 2021 11:35:47 GMT-08:00

Cerebrovascular Response during Acute Exercise in Kidney Transplant Recipients

Ward, Jaimie L. — Wed, 06 Oct 2021 11:36:40 GMT-07:00

Monitoring Daily Ultrafiltration in Automated Peritoneal Dialysis

Eibensteiner, Fabian — Fri, 10 Dec 2021 07:07:23 GMT-08:00

Trial Outcomes in Glomerular Diseases

Troost, Jonathan P. — Thu, 30 Dec 2021 10:19:16 GMT-08:00

Waitlist Mortality for Second Kidney Transplants

Fallahzadeh, Mohammad Kazem — Wed, 29 Dec 2021 02:53:31 GMT-08:00

Accessibility of Nutrition Care for Kidney Disease Worldwide

Iyengar, Arpana — Mon, 03 Jan 2022 02:49:53 GMT-08:00

Optimizing Renin-Angiotensin System Inhibitor Use in CKD

Chang, Tara I. — Wed, 17 Nov 2021 07:41:13 GMT-08:00

The Kidney in Normal Aging

Denic, Aleksandar — Wed, 20 Oct 2021 07:26:37 GMT-07:00

Assessing Global Kidney Nutrition Care

Wang, Angela Yee-Moon — Mon, 03 Jan 2022 01:48:20 GMT-08:00

Guidelines for Genetic Testing and Management of Alport Syndrome

Savige, Judy — Mon, 20 Dec 2021 06:22:07 GMT-08:00

Genetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3–COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.

Terlipressin: Hopes Fulfilled or Dashed?

Pichler, Raimund H. — Wed, 17 Nov 2021 10:25:50 GMT-08:00

Waiting Time for Second Kidney Transplantation and Mortality

Kainz, Alexander — Wed, 29 Dec 2021 08:17:49 GMT-08:00

Protection against SARS-CoV-2 Variants with COVID-19 Vaccination in Kidney Transplant Recipients

Bertrand, Dominique — Wed, 22 Dec 2021 11:26:04 GMT-08:00

Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease

Schmidt, Insa M. — Wed, 10 Nov 2021 09:47:59 GMT-08:00

An Honorable and Ongoing Fight

Conway, Paul T. — Wed, 22 Dec 2021 11:26:05 GMT-08:00

Kidney Failure Risk Equation and Cost of Care in Patients with Chronic Kidney Disease

Prasad, Bhanu — Thu, 30 Dec 2021 10:48:48 GMT-08:00

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis

Wenderfer, Scott E. — Wed, 03 Nov 2021 09:34:38 GMT-07:00

Nocturnal Dipping and Left Ventricular Mass Index in the Chronic Kidney Disease in Children Cohort

Bakhoum, Christine Y. — Fri, 12 Nov 2021 09:18:39 GMT-08:00

Post-Transplant Pregnancy and Contraception

Klein, Christina L. — Wed, 17 Mar 2021 12:46:02 GMT-07:00

Placed in a historical context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.

Bone and Mineral Disease in Kidney Transplant Recipients

Khairallah, Pascale — Mon, 14 Jun 2021 11:46:48 GMT-07:00

After kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.

Estimating Nephron Number from Biopsies: Impact on Clinical Studies

Morozov, Darya — Wed, 10 Nov 2021 10:48:42 GMT-08:00

Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial

Agarwal, Rajiv — Wed, 03 Nov 2021 09:34:18 GMT-07:00

Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia

Goodman, William G. — Wed, 03 Nov 2021 09:34:18 GMT-07:00

Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKD

Lioufas, Nicole M. — Wed, 13 Oct 2021 08:38:50 GMT-07:00

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

Lee, Yu Ho — Mon, 01 Nov 2021 08:27:53 GMT-07:00

This Month's Highlights

American Society of Nephrology — Thu, 30 Dec 2021 10:00:29 GMT-08:00

Nudging Behavioral Economics into Nephrology Care Delivery Research

Wilk, Adam S. — Thu, 30 Dec 2021 10:00:29 GMT-08:00

GWAS in Mice Maps Susceptibility to HIV-Associated Nephropathy to the Ssbp2 Locus

Steers, Nicholas J. — Fri, 10 Dec 2021 07:22:40 GMT-08:00

Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans

Ruhl, A. Parker — Wed, 27 Oct 2021 10:52:53 GMT-07:00

Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States

Horimoto, Andrea R.V.R. — Wed, 20 Oct 2021 07:19:19 GMT-07:00

Real-World Effectiveness and Immunogenicity of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Patients on Hemodialysis

Sibbel, Scott — Wed, 17 Nov 2021 10:26:37 GMT-08:00

mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation

Kaminski, Hannah — Mon, 01 Nov 2021 08:27:53 GMT-07:00

Effect of Nudge-Based Intervention on Adherence to Physician Visit Recommendations and Early Health Outcomes among Individuals Identified with Chronic Kidney Disease in Screens

Fukuma, Shingo — Mon, 13 Dec 2021 03:46:39 GMT-08:00

We Must all Join the Effort to Dismantle Environmental Racism

Al-Aly, Ziyad — Wed, 17 Nov 2021 10:26:37 GMT-08:00

Three-Dimensional Visualization of the Podocyte Actin Network Using Integrated Membrane Extraction, Electron Microscopy, and Machine Learning

Qu, Chengqing — Wed, 10 Nov 2021 10:48:42 GMT-08:00

Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis

Ichii, Osamu — Fri, 22 Oct 2021 10:35:33 GMT-07:00

Disarming the Old Foe. Restoring T-Cell Immune Function with mTor-Inhibitors to Tackle Cytomegalovirus Infection

Bestard, Oriol — Thu, 30 Dec 2021 10:00:29 GMT-08:00

A Novel Pathological Mechanism of Tertiary Lymphoid Structure Formation in the Renal Pelvis

Yamamoto, Shinya — Mon, 13 Dec 2021 01:40:58 GMT-08:00

Genome-wide Admixture Mapping of eGFR and CKD Identify European and African Ancestry-of-Origin Loci in US Hispanics/Latinos

Nestor, Jordan G. — Tue, 14 Dec 2021 05:48:41 GMT-08:00

Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease

Butt, Linus — Wed, 01 Dec 2021 09:28:12 GMT-08:00

Correction: Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells

American Society of Nephrology — Thu, 30 Dec 2021 10:00:29 GMT-08:00

Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

Little, Melissa H. — Wed, 17 Nov 2021 10:26:37 GMT-08:00

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.

Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology

Watts, Andrew J.B. — Wed, 03 Nov 2021 09:34:18 GMT-07:00

COVID-19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis

Garcia, Pablo — Wed, 13 Oct 2021 08:38:50 GMT-07:00

Quantitative Super-Resolution Microscopy Reveals Promoting Mitochondrial Interconnectivity Protects against AKI

Taguchi, Kensei — Wed, 13 Oct 2021 11:48:09 GMT-07:00

The Sisyphean Task of Getting the Arteriovenous Fistula to Mature

Bartolomeo, Korey — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Pathogenic LAMA5 Variants and Kidney Disease

Savige, Judy — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Challenges, Facilitators, and Recommendations for Implementation of Home Dialysis in the Veterans Health Administration: Patient, Caregiver, and Clinician Perceptions

Jones, Lindsey A. — Wed, 22 Sep 2021 05:30:15 GMT-07:00

Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation

Akalin, Enver — Tue, 28 Sep 2021 06:18:54 GMT-07:00

Eosinophilia and Skin Rash in a Patient with Uncontrolled Hypertension and AKI

Aklilu, Abinet M. — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Scarce Health Care Resources and Equity during COVID-19: Lessons from the History of Kidney Failure Treatment

Butler, Catherine R. — Sat, 23 Oct 2021 06:07:33 GMT-07:00

Suitability for Kidney Transplantation in AL Amyloidosis: A Survey Study of Transplant and Amyloidosis Physicians

Lam, Robert — Thu, 14 Oct 2021 12:46:20 GMT-07:00

The In-Center Hemodialysis Unit, Yet Another Obstacle to Home Dialysis

Lynch, Matthew R. — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Impact of Previous Tunneled Vascular Catheters and their Location on Upper Limb Arteriovenous Fistula Function

Diep, Jason — Thu, 07 Oct 2021 01:29:17 GMT-07:00

Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis

Bardossy, Ana Cecilia — Wed, 22 Sep 2021 05:30:15 GMT-07:00

An Unusual Cause of AKI in a Kidney Transplant Patient with Merkel Cell Cancer

Wu, Henry H.L. — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Course Corrections for Clinical AI

DeGrave, Alex J. — Mon, 27 Sep 2021 01:35:00 GMT-07:00

Autosomal Dominant Polycystic Kidney Disease Prevalence among a Racially Diverse United States Population, 2002 through 2018

Aung, Thet T. — Wed, 22 Sep 2021 05:30:15 GMT-07:00

Global Perspective on Kidney Transplantation: Brazil

Cristelli, Marina Pontello — Thu, 07 Oct 2021 01:29:17 GMT-07:00

Optimizing the Electronic Health Record for Clinical Research: Has the Time Come?

Rheault, Michelle N. — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Polycystic Kidney Disease in the Real World

Chapman, Arlene B. — Thu, 30 Dec 2021 05:30:29 GMT-08:00

Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial)

Piryani, Ameet K. — Mon, 27 Sep 2021 01:35:00 GMT-07:00

The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities

Pattharanitima, Pattharawin — Thu, 14 Oct 2021 12:46:20 GMT-07:00

Acute Onset of Nausea, Vomiting and Left Flank Pain in a Hemodialysis Patient

Gill, Jasmeet — Thu, 30 Dec 2021 05:30:29 GMT-08:00

SGLT2 Inhibitors: Physiology and Pharmacology

Wright, Ernest M. — Fri, 17 Sep 2021 09:47:50 GMT-07:00

SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 g (1 mol) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream, where theyremain in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50%–60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.

Clear Evidence of LAMA5 Gene Biallelic Truncating Variants Causing Infantile Nephrotic Syndrome

Taniguchi, Yukimasa — Fri, 15 Oct 2021 12:51:19 GMT-07:00

Characteristics Associated with Variation in Corticosteroid Exposure in Children with Steroid-Sensitive Nephrotic Syndrome: Results from a Canadian Longitudinal Study

Rodriguez-Lopez, Sara — Thu, 23 Sep 2021 06:29:13 GMT-07:00

Complement Activation Fragments Are Increased in Critically Ill Pediatric Patients with Severe AKI

Stenson, Erin K. — Thu, 07 Oct 2021 11:02:39 GMT-07:00

Validating a Computable Phenotype for Nephrotic Syndrome in Children and Adults Using PCORnet Data

Oliverio, Andrea L. — Mon, 27 Sep 2021 01:35:00 GMT-07:00

Should We Let Dialysis Patients Eat Their Fruits and Veggies?

Kovesdy, Csaba P. — Wed, 01 Dec 2021 02:31:10 GMT-08:00

Telehealth and Kidney Disease Care

Lew, Susie Q. — Tue, 07 Dec 2021 11:35:23 GMT-08:00

Time to Abandon Kidney Biopsy to Diagnose Membranous Nephropathy?

Ronco, Pierre — Mon, 15 Nov 2021 05:39:42 GMT-08:00

When and How Is It Possible to Stop Therapy in Patients with Lupus Nephritis

Moroni, Gabriella — Wed, 23 Jun 2021 10:54:11 GMT-07:00

Glucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE and lupus nephritis. The refined use of these drugs over the years has allowed us to obtain stable disease remission and improvement of long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review, we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal, around one-quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission for even 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.

Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States

Krissberg, Jill R. — Wed, 20 Oct 2021 02:00:09 GMT-07:00

Kidney Replacement Therapy for Patients Requiring Cardiopulmonary Bypass Support during Cardiac Surgery

Stevens, Jacob S. — Wed, 27 Oct 2021 08:27:54 GMT-07:00

Correction: Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood

American Society of Nephrology — Tue, 07 Dec 2021 11:35:23 GMT-08:00

APOL1 Kidney Risk Variants and Acute Kidney Injury in Those with COVID-19

Gadegbeku, Crystal A. — Tue, 07 Dec 2021 11:35:23 GMT-08:00

Humoral Response to BNT162b2 mRNA SARS-CoV-2 Vaccine in Patients with Nondialysis Chronic Kidney Disease

Kervella, Delphine — Wed, 03 Nov 2021 09:34:38 GMT-07:00

Association of Polypharmacy with Kidney Disease Progression in Adults with CKD

Kimura, Hiroshi — Mon, 15 Nov 2021 04:21:19 GMT-08:00

Food Insecurity and Kidney Disease

Mokiao, Reya — Wed, 13 Oct 2021 08:24:05 GMT-07:00

The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function

Waijer, Simke W. — Wed, 01 Dec 2021 11:42:19 GMT-08:00

Classification of Uremic Toxins and Their Role in Kidney Failure

Rosner, Mitchell H. — Wed, 07 Jul 2021 11:09:02 GMT-07:00

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Patient Views on Telehealth for Kidney Disease Care

Glennon, Julie — Tue, 07 Dec 2021 11:35:23 GMT-08:00

Humoral Response to One and Two Doses of ChAdOx1-S Vaccine in Patients on Hemodialysis

Yadav, Ashok Kumar — Mon, 20 Sep 2021 10:40:31 GMT-07:00

APOL1 Risk Variants and Acute Kidney Injury in Black Americans with COVID-19

Larsen, Christopher P. — Tue, 07 Dec 2021 11:35:23 GMT-08:00

Atrasentan: The Difficult Task of Integrating Endothelin A Receptor Antagonists into Current Treatment Paradigm for Diabetic Kidney Disease

Ortiz, Alberto — Wed, 01 Dec 2021 01:40:40 GMT-08:00

What Is the Best Maintenance Therapy for ANCA Vasculitis?

Woerner, Katti — Tue, 09 Nov 2021 07:30:46 GMT-08:00

Collectin11 and Complement Activation in IgA Nephropathy

Wei, Min — Wed, 06 Oct 2021 11:13:55 GMT-07:00

Video-Based Telemedicine for Kidney Disease Care

Young, Ann — Tue, 07 Dec 2021 11:35:23 GMT-08:00

A Body Size–Adjusted Maximum Ultrafiltration Rate Warning Level Is Not Equitable for Larger Patients

Daugirdas, John T. — Thu, 11 Nov 2021 06:46:19 GMT-08:00

Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy

Bobart, Shane A. — Mon, 15 Nov 2021 05:12:51 GMT-08:00

Change in Physical Activity and Function in Patients with Baseline Advanced Nondialysis CKD

Rampersad, Christie — Mon, 25 Oct 2021 07:23:51 GMT-07:00

Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis

Bernier-Jean, Amelie — Wed, 01 Dec 2021 02:01:59 GMT-08:00

Post-Transplant Cardiovascular Disease

Birdwell, Kelly A. — Thu, 23 Sep 2021 06:53:28 GMT-07:00

Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.

Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney Transplantation

Ibrahim, Hassan N. — Tue, 23 Mar 2021 07:48:28 GMT-07:00

Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.

Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal Dysfunction

Liu, Hao — Wed, 22 Sep 2021 10:24:04 GMT-07:00

It Is Time for Patient-Reported Outcome Measures to Be Included in the Approval Process for Solid Organ Transplant Medications

Formica, Richard N. — Tue, 30 Nov 2021 06:14:42 GMT-08:00

Back to the Future: The Role of Metabolic Studies in Therapeutic Advances

Milliner, Dawn S. — Tue, 30 Nov 2021 06:14:42 GMT-08:00

This Month's Highlights

American Society of Nephrology — Tue, 30 Nov 2021 06:14:42 GMT-08:00

Making the Connection

Oxburgh, Leif — Wed, 17 Nov 2021 08:13:16 GMT-08:00

B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Schrezenmeier, Eva — Tue, 19 Oct 2021 05:27:18 GMT-07:00

Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel–Mediated Sodium Transport in Collecting Duct Principal Cells

Dizin, Eva — Wed, 06 Oct 2021 09:49:36 GMT-07:00

Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing

Zhang, Zhengmao — Fri, 29 Oct 2021 09:20:56 GMT-07:00

Generation of Distal Renal Segments Involves a Unique Population of Aqp2+ Progenitor Cells

Gao, Chao — Tue, 19 Oct 2021 05:27:18 GMT-07:00

Conversion from Calcineurin Inhibitor– to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b Trial

Budde, Klemens — Wed, 27 Oct 2021 10:52:52 GMT-07:00

COVID-19 Vaccination in Kidney Transplant Recipients: An Ounce Pre-Transplant is Worth a Pound Post-Transplant

Chandran, Sindhu — Tue, 30 Nov 2021 06:14:42 GMT-08:00

Removing Race from Kidney Disease Diagnosis

Quaggin, Susan E. — Tue, 09 Nov 2021 06:00:08 GMT-08:00

Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study

Van Praet, Jens — Wed, 29 Sep 2021 09:52:14 GMT-07:00

Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy

Xie, Di — Wed, 20 Oct 2021 07:19:19 GMT-07:00

Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular Injury

Schunk, Stefan J. — Wed, 29 Sep 2021 09:52:14 GMT-07:00

Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection

Cravedi, Paolo — Fri, 01 Oct 2021 02:00:11 GMT-07:00

IgA Nephropathy Needs a Diagnostic Marker of Immunologic Activity to Select the Right Patients for Immunotherapies

Hilhorst, Marc — Wed, 17 Nov 2021 09:34:17 GMT-08:00

CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients

Lamarthée, Baptiste — Tue, 30 Nov 2021 06:14:42 GMT-08:00

Global Health Education in Nephrology: The Time has Come

Ingenhoff, Rebecca — Wed, 13 Oct 2021 08:38:50 GMT-07:00

A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease

Delgado, Cynthia — Thu, 23 Sep 2021 09:30:08 GMT-07:00

Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial

Sparks, Jeffrey A. — Wed, 22 Sep 2021 10:24:04 GMT-07:00

CHOP-ASO Ameliorates Glomerular and Tubular Damage on Top of ACE Inhibition in Diabetic Kidney Disease

Shahzad, Khurrum — Fri, 03 Sep 2021 09:49:58 GMT-07:00

Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pHo

Yoon, Joonho — Wed, 22 Sep 2021 10:24:03 GMT-07:00

Polygenic Risk Scores for Kidney Function and Their Associations with Circulating Proteome, and Incident Kidney Diseases

Yu, Zhi — Tue, 21 Sep 2021 10:35:12 GMT-07:00

IL-17 Receptor C Signaling Controls CD4+ TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney Diseases

Schmidt, Tilman — Tue, 30 Nov 2021 06:14:42 GMT-08:00

Endogenous Oxalate Production in Primary Hyperoxaluria Type 1 Patients

Garrelfs, Sander F. — Fri, 22 Oct 2021 10:35:33 GMT-07:00

Patient Activation Measure in Dialysis-Dependent Patients in the United States

Cukor, Daniel — Wed, 01 Sep 2021 02:00:10 GMT-07:00

Use of a Smartphone Camera at the Bedside to Assess Adequacy of Kidney Biopsies

Singh, Gurmukteshwar — Mon, 13 Sep 2021 11:27:11 GMT-07:00

Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus Nephritis

Angeletti, Andrea — Fri, 01 Oct 2021 10:37:16 GMT-07:00

Reconsidering Donor Race in Predicting Allograft and Patient Survival Among Kidney Transplant Recipients

Chong, Kelly — Thu, 19 Aug 2021 11:39:27 GMT-07:00

An Unusual Cause of AKI in a Kidney Transplant Recipient

Malhotra, Divyanshu — Wed, 24 Nov 2021 02:00:34 GMT-08:00

A Computable Phenotype for Autosomal Dominant Polycystic Kidney Disease

Kalot, Mohamad A. — Thu, 16 Sep 2021 09:50:05 GMT-07:00

Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial

Chang, Tara I. — Thu, 16 Sep 2021 09:50:05 GMT-07:00

Hematuria and Flank Pain in a Patient with Sickle Cell Trait Who Is Taking NSAIDs

Homan, Travis D. — Wed, 24 Nov 2021 02:00:34 GMT-08:00

The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair

Xu, Leyuan — Wed, 22 Sep 2021 05:30:15 GMT-07:00

AKI remains highly prevalent, yet no optimal therapy is available to prevent it or promote recovery after initial insult. Experimental studies have demonstrated that both innate and adaptive immune responses play a central role during AKI. In response to injury, myeloid cells are first recruited and activated on the basis of specific signals from the damaged microenvironment. The subsequent recruitment and activation state of the immune cells depends on the stage of injury and recovery, reflecting a dynamic and diverse spectrum of immunophenotypes. In this review, we highlight our current understanding of the mechanisms by which myeloid cells contribute to injury, repair, and fibrosis after AKI.

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: COMMENTARY

Klomjit, Nattawat — Mon, 19 Apr 2021 09:28:55 GMT-07:00

Number of Donor Renal Arteries and Early Outcomes after Deceased Donor Kidney Transplantation

Husain, S. Ali — Wed, 08 Sep 2021 01:35:20 GMT-07:00

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: PRO

Oliva-Damaso, Nestor — Mon, 19 Apr 2021 09:28:55 GMT-07:00

Deletion of Mocos Induces Xanthinuria with Obstructive Nephropathy and Major Metabolic Disorders in Mice

Sedda, Delphine — Fri, 17 Sep 2021 11:21:16 GMT-07:00

Acute Onset of Dark Urine in a Patient with LVAD Pump Dysfunction

Alstott, James — Wed, 24 Nov 2021 02:00:34 GMT-08:00

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CON

van de Logt, Anne-Els — Mon, 19 Apr 2021 09:28:55 GMT-07:00

Arteriovenous Fistula Nonmaturation: What’s the Immune System Got to Do with It?

Farrington, Crystal A. — Tue, 14 Sep 2021 11:42:21 GMT-07:00

Global Perspective on Kidney Transplantation: Spain

Crespo, Marta — Thu, 02 Sep 2021 11:34:30 GMT-07:00

Untangling the Association between Anemia Treatment and Stroke Risk in CKD

Wish, Jay B. — Wed, 24 Nov 2021 02:00:34 GMT-08:00

Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study

Lambert, Douglas C. — Thu, 09 Sep 2021 03:47:12 GMT-07:00

Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female Rats

Barsha, Giannie — Fri, 10 Sep 2021 07:52:36 GMT-07:00

Impact of AKI in Patients with Out-of-Hospital Cardiac Arrest Managed with VA ECMO

Ravipati, Prasanth — Wed, 08 Sep 2021 01:35:20 GMT-07:00

Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of d-Serine

Iwata, Yukimasa — Thu, 09 Sep 2021 07:23:06 GMT-07:00

Declined Offers for Deceased Donor Kidneys Are Not an Independent Reflection of Organ Quality

King, Kristen L. — Tue, 24 Aug 2021 12:25:50 GMT-07:00

Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL Trial

Mark, Patrick B. — Thu, 16 Sep 2021 11:27:18 GMT-07:00

Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients

Daniels, Jaclyn R. — Thu, 09 Sep 2021 03:47:12 GMT-07:00

What to Do with Race: Social Factors and Evaluating Clinical Risk in Kidney Transplantation

McKinney, Warren T. — Tue, 05 Oct 2021 12:51:16 GMT-07:00

Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases

Caza, Tiffany N. — Thu, 16 Sep 2021 09:50:05 GMT-07:00

Myeloid Heterogeneity in Kidney Disease as Revealed through Single-Cell RNA Sequencing

Bell, Rachel M.B. — Thu, 02 Sep 2021 11:34:30 GMT-07:00

Kidney disease represents a global health burden of increasing prevalence and is an independent risk factor for cardiovascular disease. Myeloid cells are a major cellular compartment of the immune system; they are found in the healthy kidney and in increased numbers in the damaged and/or diseased kidney, where they act as key players in the progression of injury, inflammation, and fibrosis. They possess enormous plasticity and heterogeneity, adopting different phenotypic and functional characteristics in response to stimuli in the local milieu. Although this inherent complexity remains to be fully understood in the kidney, advances in single-cell genomics promise to change this. Specifically, single-cell RNA sequencing (scRNA-seq) has had a transformative effect on kidney research, enabling the profiling and analysis of the transcriptomes of single cells at unprecedented resolution and throughput, and subsequent generation of cell atlases. Moving forward, combining scRNA- and single-nuclear RNA-seq with greater-resolution spatial transcriptomics will allow spatial mapping of kidney disease of varying etiology to further reveal the patterning of immune cells and nonimmune renal cells. This review summarizes the roles of myeloid cells in kidney health and disease, the experimental workflow in currently available scRNA-seq technologies, and published findings using scRNA-seq in the context of myeloid cells and the kidney.

Global Perspective on Kidney Transplantation: United States

Wang, Jeffrey H. — Thu, 19 Aug 2021 11:39:27 GMT-07:00

Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes

Ville, Simon — Fri, 08 Oct 2021 12:18:10 GMT-07:00

Coffee Metabolites and Kidney Disease

Cornelis, Marilyn C. — Thu, 04 Nov 2021 01:57:04 GMT-07:00

ANCA Vasculitis Treatment in the Dialysis Patient

Hendren, Elizabeth — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Muscle Abnormalities with Kidney Failure

Bárány, Peter — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Could This Be Alport Syndrome?

Lennon, Rachel — Tue, 13 Apr 2021 08:05:32 GMT-07:00

Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients

Knobbe, Tim J. — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis

Kauffmann, Maëlis — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Family Members’ Understanding of the End-of-Life Wishes of People Undergoing Maintenance Dialysis

Saeed, Fahad — Fri, 10 Sep 2021 02:00:11 GMT-07:00

Kidney Disease among People Who Are Incarcerated

Murphy, Matthew — Wed, 16 Jun 2021 10:53:39 GMT-07:00

CKD affects 15% of US adults and is associated with higher morbidity and mortality. CKD disproportionately affects certain populations, including racial and ethnic minorities and individuals from disadvantaged socioeconomic backgrounds. These groups are also disproportionately affected by incarceration and barriers to accessing health services. Incarceration represents an opportunity to link marginalized individuals to CKD care. Despite a legal obligation to provide a community standard of care including the screening and treatment of individuals with CKD, there is little evidence to suggest systematic efforts are in place to address this prevalent, costly, and ultimately fatal condition. This review highlights unrealized opportunities to connect individuals with CKD to care within the criminal justice system and as they transition to the community, and it underscores the need for more evidence-based strategies to address the health effect of CKD on over-represented communities in the criminal justice system.

Understanding Fatigue with Kidney Disease

Forfang, Derek — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation

Souweine, Jean-Sébastien — Mon, 08 Nov 2021 11:40:20 GMT-08:00

Poly-IgA Complexes and Disease Severity in IgA Nephropathy

Zhang, Xue — Mon, 04 Oct 2021 11:25:32 GMT-07:00

Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease

He, William J. — Thu, 04 Nov 2021 01:41:55 GMT-07:00

The Future Nephrology Workforce: There Will Be One

Parker, Mark G. — Mon, 19 Jul 2021 10:54:28 GMT-07:00

Training Nephrology Fellows in Home Dialysis in the United States

Gupta, Nupur — Wed, 21 Jul 2021 07:02:00 GMT-07:00

COVID-19–Associated Mortality among Kidney Transplant Recipients and Candidates in the United States

Mohan, Sumit — Wed, 29 Sep 2021 01:48:33 GMT-07:00

Humoral Response to mRNA versus an Adenovirus Vector-Based SARS-CoV-2 Vaccine in Dialysis Patients

Mulhern, Jeffrey G. — Mon, 26 Jul 2021 10:16:49 GMT-07:00

Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19

Hassler, Luise — Mon, 14 Jun 2021 12:53:52 GMT-07:00

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19–associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19–associated kidney disease.

COVID-19 Vaccination Imperatives in People on Maintenance Dialysis

Blake, Peter G. — Mon, 19 Jul 2021 10:54:28 GMT-07:00

Kidney Effects of Empagliflozin in People with Type 1 Diabetes

Cherney, David Z.I. — Fri, 17 Sep 2021 10:39:07 GMT-07:00

C3 Glomerulopathy and Related Disorders in Children

Wong, Edwin K.S. — Wed, 22 Sep 2021 10:24:42 GMT-07:00

Recurrent Glomerular Disease after Kidney Transplantation

Uffing, Audrey — Fri, 22 Oct 2021 06:42:10 GMT-07:00

Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.

Chronic Allograft Injury

Langewisch, Eric — Mon, 05 Apr 2021 07:48:23 GMT-07:00

With the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.

Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR Trial

Heerspink, Hiddo J. L. — Wed, 22 Sep 2021 10:24:03 GMT-07:00

PodoSighter: A Cloud-Based Tool for Label-Free Podocyte Detection in Kidney Whole-Slide Images

Govind, Darshana — Fri, 03 Sep 2021 09:49:58 GMT-07:00

Donor-Specific Antibody Is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified as No Rejection

Madill-Thomsen, Katelynn S. — Mon, 12 Jul 2021 10:21:53 GMT-07:00

Podocyte Aging: Why and How Getting Old Matters

Shankland, Stuart J. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

The effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population’s increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.

Incidence of Arteritis and Peritubular Capillaritis in ANCA-associated Vasculitis

Hakroush, Samy — Fri, 15 Oct 2021 06:20:56 GMT-07:00

Tribute to Barbara T. Murphy

Quaggin, Susan E. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Understanding Risks and Our Responsibility to Living Donors

Gill, John S. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Predictive Enrichment in Kidney RCTs: Is Albuminuria the Answer?

Odutayo, Ayodele — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Beyond Transcription Factors: Remodeling Chromatin in the Metanephric Mesenchyme

El-Dahr, Samir S. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 29 Oct 2021 12:45:34 GMT-07:00

The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis

Moran, Sarah M. — Mon, 13 Sep 2021 11:27:11 GMT-07:00

Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors

Ibrahim, Hassan N. — Thu, 21 Oct 2021 07:54:09 GMT-07:00

Authors’ Reply

Harris, Raymond C. — Tue, 05 Oct 2021 05:51:20 GMT-07:00

Authors’ Reply

Bunnapradist, Suphamai — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Need for a Validation Study before Using the Two-Step Algorithm for dd-cfDNA to Screen for Acute Rejection

Gupta, Aditi — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD

Walker, Joshua A. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Heterogenous Role of IRF4 in Kidney Fibrosis

Liu, Zhenyu — Tue, 05 Oct 2021 06:18:34 GMT-07:00

Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis

Müller-Deile, Janina — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Analysis of Performance Trends from 2010–2019 on the American Board of Internal Medicine Nephrology Certifying Exam

Berns, Jeffrey S. — Wed, 27 Oct 2021 01:33:36 GMT-07:00

Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease

Mair, Robert D. — Wed, 18 Aug 2021 09:07:10 GMT-07:00

Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell Maintenance

Li, Jun — Fri, 29 Oct 2021 12:45:34 GMT-07:00

The Art and Science of Medicine … and Standardized Test Scores

Quaggin, Susan E. — Wed, 27 Oct 2021 01:33:37 GMT-07:00

Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse Models

Zhang, Xiaoqin — Fri, 29 Oct 2021 12:45:34 GMT-07:00

mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy

Schlingmann, Karl P. — Mon, 04 Oct 2021 12:36:06 GMT-07:00

Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis

Idrovo, Alexandra — Mon, 13 Sep 2021 11:27:11 GMT-07:00

Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease

Quinn, Ghazal Z. — Wed, 04 Aug 2021 12:11:01 GMT-07:00

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis

Lacson, Eduardo — Wed, 04 Aug 2021 12:11:00 GMT-07:00

Kidney Outcomes in Long COVID

Bowe, Benjamin — Wed, 01 Sep 2021 06:00:08 GMT-07:00

Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic

Wetmore, James B. — Fri, 17 Sep 2021 10:39:33 GMT-07:00

Longitudinal Outcomes of COVID-19–Associated Collapsing Glomerulopathy and Other Podocytopathies

Kudose, Satoru — Wed, 20 Oct 2021 07:19:19 GMT-07:00

Large Between-Patient Variability in eGFR Decline before Clinical Trial Enrollment and Impact on Atrasentan’s Efficacy: A Post Hoc Analysis from the SONAR Trial

Waijer, Simke W. — Fri, 20 Aug 2021 10:25:58 GMT-07:00

Testing of Worn Face Masks for Timely Diagnosis of SARS-CoV-2 in Hemodialysis Patients

Wang, Xiaoling — Mon, 19 Jul 2021 11:44:34 GMT-07:00

Impaired Humoral but Substantial Cellular Immune Response to Variants of Concern B1.1.7 and B.1.351 in Hemodialysis Patients after Vaccination with BNT162b2

Thieme, Constantin J. — Fri, 29 Oct 2021 12:45:34 GMT-07:00

Unexpected Kidney Imaging in a Patient with UTI

Gill, Jasmeet — Thu, 28 Oct 2021 08:50:34 GMT-07:00

Still Learning from Our Patients: Hypokalemia in Patients with Lupus Nephritis

Rodan, Aylin R. — Thu, 28 Oct 2021 08:50:34 GMT-07:00

POCUS for Nephrologists: Basic Principles and a General Approach

Koratala, Abhilash — Thu, 05 Aug 2021 09:25:28 GMT-07:00

Point-of-care ultrasonography (POCUS) has evolved as a valuable adjunct to physical examination in the recent past and various medical specialties have embraced it. However, POCUS training and scope of practice remain relatively undefined in nephrology. The utility of diagnostic POCUS beyond kidney and vascular access is under-recognized. Assessment of fluid status is a frequent dilemma faced by nephrologists in day-to-day practice where multiorgan POCUS can enhance the sensitivity of conventional physical examination. POCUS also reduces fragmentation of care, facilitates timely diagnosis, and expedites management. Although the need for further imaging studies is obviated in selected patients, POCUS is not meant to serve as an alternative to consultative imaging. In addition, the utility of POCUS depends on the skills and experience of the operator, which in turn depend on the quality of training. In this review, we discuss the rationale behind nephrologists performing POCUS, discuss patient examples to illustrate the basic principles of focused ultrasonography, and share our experience-based opinion about developing a POCUS training program at the institutional level.

A Randomized Intervention to Assess the Effectiveness of an Educational Video on Organ Donation Intent

Molmenti, Ernesto P. — Wed, 28 Jul 2021 09:58:52 GMT-07:00

d-Serine Mediates Cellular Proliferation for Kidney Remodeling

Hesaka, Atsushi — Mon, 16 Aug 2021 01:27:39 GMT-07:00

Moving Hearts and Minds: Video Intervention To Improve Organ Donor Registration Intent

Ong, Song — Thu, 28 Oct 2021 08:50:34 GMT-07:00

A Blueprint for an Integrated Point-of-Care Ultrasound Curriculum for Nephrology Trainees

Koratala, Abhilash — Fri, 13 Aug 2021 12:53:58 GMT-07:00

Point-of-care ultrasonography (POCUS) is a limited ultrasound study performed by the clinician at the bedside as a component or an adjunct to physical examination. POCUS has multiple applications in nephrology practice, including evaluation of obstructive uropathy, objective assessment of volume status, arteriovenous access assessment, and procedural guidance. However, unlike specialties such as emergency medicine, POCUS training is not yet integrated into most nephrology fellowship curricula, and the sonographic applications taught vary widely among fellowship programs. In this article, we have used our institutional experience to provide a roadmap or blueprint for nephrology programs looking to create a POCUS program. We provide an overview of the curriculum, including the basic organization, applications taught, online resources, milestone development, and quality assessment. We also discuss the nuances of POCUS workflow and perspectives on billing for these limited studies. In addition, we share the evaluation forms and sample documentation we use in our program. Future support, in the form of endorsed nephrology society guidelines, is needed before POCUS training is universally incorporated across nephrology fellowship programs.

Global Perspective on Kidney Transplantation: France

Divard, Gillian — Fri, 06 Aug 2021 11:35:17 GMT-07:00

Perceptions of Multidisciplinary Renal Team Members toward Home Dialysis Therapies

Poinen, Krishna — Mon, 09 Aug 2021 01:20:57 GMT-07:00

Global Perspective on Kidney Transplantation: Australia

Wyld, Melanie L.R. — Thu, 05 Aug 2021 09:25:28 GMT-07:00

Multi-Target Drugs for Kidney Diseases

Imig, John D. — Mon, 02 Aug 2021 01:50:51 GMT-07:00

Kidney diseases such as AKI, CKD, and GN can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past 10 years, in silico design of drugs has allowed for multi-target drugs to progress quickly from concept to reality. Several multi-target drugs have been made successfully to target AA pathways and transcription factors for the treatment of inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal TGF-β signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

Block, Geoffrey A. — Fri, 27 Aug 2021 11:33:29 GMT-07:00

Acute Kidney Injury in a Patient on High-dose Glucocorticoid Therapy

DiFranza, Lanny T. — Thu, 28 Oct 2021 08:50:34 GMT-07:00

Hemoglobinuria in the Early Poststem-Cell–Transplant Period: Risk Factors and Association with Outcomes

Kompotiatis, Panagiotis — Wed, 25 Aug 2021 09:57:54 GMT-07:00

Global Dialysis Perspective: Iceland

Emilsdottir, Arna R. — Fri, 06 Aug 2021 11:35:17 GMT-07:00

The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKI

Tolan, Nicole V. — Wed, 14 Jul 2021 12:17:39 GMT-07:00

Kidney Injury in a Patient with Hypocomplementemia and Diffuse Lymphadenopathy

Rehan, Anam — Thu, 28 Oct 2021 08:50:34 GMT-07:00

Idiopathic Hypokalemia in Lupus Nephritis: A Newly Recognized Entity

Adomako, Emmanuel A. — Fri, 06 Aug 2021 01:32:05 GMT-07:00

Monocytes and Macrophages in Kidney Transplantation and Insights from Single Cell RNA-Seq Studies

Malone, Andrew F. — Tue, 17 Aug 2021 01:18:43 GMT-07:00

Single-cell RNA sequencing (scRNA-seq) is a powerful technology that allows for the identification of minority cell types in complex tissues, such as immune cells in the kidney. Previously, gene expression from infrequent cell types was missed using bulk RNA-sequencing methods due to an averaging effect. Additionally, scRNA-seq facilitates assignment of cell origin in a sample, a shortcoming of previous bulk sequencing technologies. Thus, scRNA-seq is ideal to study the immune cell landscape and the alloimmune response in the human kidney transplant. However, there are few studies published to date. Macrophages are known to play an important role in health and disease in the kidney. Furthermore, it is known that macrophages play key roles in rejection of the kidney transplant. The definition, ontogeny, and function of these cells is complex and nomenclature has evolved as new technologies have become available. In this review, an overview is provided of monocyte and macrophage nomenclature, ontogeny, and function, with a specific focus on kidney transplantation, and including novel scRNA-seq findings. scRNA-seq offers an unbiased transcriptional approach to defining macrophages and provides insights into macrophage ontogeny and function not possible with contemporary methods.

Identifying Acute Kidney Injury in the Outpatient Setting: The First Step

Goldstein, Stuart L. — Thu, 28 Oct 2021 08:50:34 GMT-07:00

Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism

Terabayashi, Takeshi — Fri, 16 Jul 2021 01:27:01 GMT-07:00

Value-Based Care in Nephrology: The Kidney Care Choices Model and Other Reforms

Jain, Gaurav — Mon, 16 Aug 2021 10:48:11 GMT-07:00

The Advancing American Kidney Health (AAKH) initiative has reinvigorated the focus on improving the care of patients with advanced CKD. Multiple interventions have been planned, focusing on education campaigns for both clinicians and patients, delaying the progression of kidney disease and improving utilization of home dialysis modalities and kidney transplantation. Value-based care models for patients with advanced kidney disease are being rolled out, with the ESKD treatment choices model starting in January 2021, and the Kidney Care Choices model planned to start in January 2022. There is increasing emphasis on the role of the nephrologist as the “captain of the ship,” leading efforts in care coordination as physician leaders. The transplant reforms have focused on changes to organ procurement organizations aiming to increase availability of organs, and transplants performed, both deceased and living donor, and removing financial disincentives from live organ donation. The American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) are partnering with the Department of Health and Human Services to develop educational material for clinicians and patients. In this review, we discuss these reforms, potential challenges that have arisen, and potential solutions, with emphasis on the Kidney Care Choices model.

Soluble Klotho and Incident Hypertension

Drew, David A. — Thu, 23 Sep 2021 06:53:28 GMT-07:00

Race and Evaluation for a Kidney Transplant

Adams, Artemeshia — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Organizational Characteristics Associated with High Performance in Medicare’s Comprehensive End-Stage Renal Disease Care Initiative

Drewry, Kelsey M. — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease

Edwards, Nicola C. — Mon, 30 Aug 2021 10:34:54 GMT-07:00

Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft Status

Lubetzky, Michelle L. — Tue, 27 Apr 2021 08:22:12 GMT-07:00

Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.

Transforming the Care of Patients with Diabetic Kidney Disease

Brosius, Frank C. — Tue, 08 Jun 2021 06:52:50 GMT-07:00

Diabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease is one of the most devastating complications, increasing the risk of death more than ten-fold over the general population. Until very recently, the only drugs proven and recommended to slow the progression of diabetic kidney disease were angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, which act by inhibiting the renin-angiotensin system. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, renin-angiotensin system inhibitors have been grossly underutilized. Moreover, even when renin-angiotensin system inhibitors are used, patients still have a high residual risk of diabetic kidney disease progression. Finally, the kidney-protective effect of renin-angiotensin system inhibitors has been categorically demonstrated only in patients with macroalbuminuria included in the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trials, not in other individuals. The lack of new therapies to treat diabetic kidney disease over the past 2 decades has therefore represented a tremendous challenge for patients and health care providers alike. In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges, and possible solutions to advance kidney health, and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.

Being an ADVOCATE for People with ANCA Vasculitis

Anders, Hans-Joachim — Thu, 03 Jun 2021 10:41:09 GMT-07:00

Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients

Park, Sookhyeon — Thu, 07 Oct 2021 12:05:16 GMT-07:00

The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation

Harel, Ziv — Wed, 18 Aug 2021 09:06:52 GMT-07:00

Race-Based eGFR Assessment for Kidney Transplantation

Hoenig, Melanie P. — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Value-Based Kidney Care

Tummalapalli, Sri Lekha — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Two Can Be Better Than One

Khilnani, Calla — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Prevention of Acute Kidney Injury after Cardiac Surgery

Basu, Rajit K. — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Arterial Stiffness Is Independently Associated with Acute Kidney Injury in SPRINT

Pengshung, Michelle H. — Fri, 27 Aug 2021 09:06:27 GMT-07:00

Advancing American Kidney Health and the Role of Sodium-Glucose Cotransporter-2 Inhibitors

Li, Jiahua — Wed, 16 Jun 2021 10:53:39 GMT-07:00

Recovery after Critical Illness and Acute Kidney Injury

Vijayan, Anitha — Mon, 30 Aug 2021 08:28:42 GMT-07:00

AKI is a common complication in hospitalized and critically ill patients. Its incidence has steadily increased over the past decade. Whether transient or prolonged, AKI is an independent risk factor associated with poor short- and long-term outcomes, even if patients do not require KRT. Most patients with early AKI improve with conservative management; however, some will require dialysis for a few days, a few weeks, or even months. Approximately 10%–30% of AKI survivors may still need dialysis after hospital discharge. These patients have a higher associated risk of death, rehospitalization, recurrent AKI, and CKD, and a lower quality of life. Survivors of critical illness may also suffer from cognitive dysfunction, muscle weakness, prolonged ventilator dependence, malnutrition, infections, chronic pain, and poor wound healing. Collaboration and communication among nephrologists, primary care physicians, rehabilitation providers, physical therapists, nutritionists, nurses, pharmacists, and other members of the health care team are essential to create a holistic and patient-centric care plan for overall recovery. Integration of the patient and family members in health care decisions, and ongoing education throughout the process, are vital to improve patient well-being. From the nephrologist standpoint, assessing and promoting recovery of kidney function, and providing appropriate short- and long-term follow-up, are crucial to prevent rehospitalizations and to reduce complications. Return to baseline functional status is the ultimate goal for most patients, and dialysis independence is an important part of that goal. In this review, we seek to highlight the varying aspects and stages of recovery from AKI complicating critical illness, and propose viable strategies to promote recovery of kidney function and dialysis independence. We also emphasize the need for ongoing research and multidisciplinary collaboration to improve outcomes in this vulnerable population.

Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis

Ganesan, Lakshmi L. — Wed, 07 Jul 2021 11:09:02 GMT-07:00

Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery

Van den Eynde, Jef — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis

Bielesz, Bernhard — Wed, 01 Sep 2021 08:24:50 GMT-07:00

Transplant Clinician Opinions on Use of Race in the Estimation of Glomerular Filtration Rate

Doshi, Mona D. — Thu, 07 Oct 2021 12:05:16 GMT-07:00

Barriers and Solutions to Kidney Transplantation for the Undocumented Latinx Community with Kidney Failure

Rizzolo, Katherine — Thu, 23 Sep 2021 06:53:28 GMT-07:00

Black Race Coefficient in GFR Estimation and Prevalence of CKD-Related Complications

Walther, Carl P. — Mon, 14 Jun 2021 11:46:48 GMT-07:00

GLP-1 Receptor Agonists in Diabetic Kidney Disease

Michos, Erin D. — Tue, 13 Apr 2021 08:05:32 GMT-07:00

Considerations in the Study of Body Mass Index Variability

Gregg, L. Parker — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Urine APOL1 Isoforms Reflect Plasma-Derived Liver-Synthesized Proteins

Althage, Magnus — Wed, 23 Jun 2021 11:32:46 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Toward Antiracist Reimbursement Policy in End-Stage Kidney Disease: From Equality to Equity

Taylor, Kathryn — Mon, 12 Jul 2021 10:21:52 GMT-07:00

Long-Term Outcomes of Children Undergoing Dialysis-treated AKI: Some Opinions and Prospects

Wei, Shiyuan — Thu, 16 Sep 2021 01:36:25 GMT-07:00

Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial Cells

Liu, Zhiheng — Wed, 23 Jun 2021 02:05:28 GMT-07:00

Racial Inequalities in Drinking Water Lead Exposure: A Wake-Up Call to Protect Patients with End Stage Kidney Disease

Nigra, Anne E. — Mon, 20 Sep 2021 11:11:45 GMT-07:00

Introducing a Special Series: Addressing Racial and Ethnic Disparities in Kidney Disease

Briggs, Josephine P. — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Erythropoietin Reduces Auto- and Alloantibodies by Inhibiting T Follicular Helper Cell Differentiation

Guglielmo, Chiara — Wed, 14 Jul 2021 09:30:45 GMT-07:00

O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular Function

Dotz, Viktoria — Mon, 14 Jun 2021 11:36:36 GMT-07:00

Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A Primer

Tin, Adrienne — Wed, 16 Jun 2021 10:31:17 GMT-07:00

Many Mendelian randomization (MR) studies have been published recently, with inferences on the causal relationships between risk factors and diseases that have potential implications for clinical research. In nephrology, MR methods have been applied to investigate potential causal relationships of traditional risk factors, lifestyle factors, and biomarkers from omics technologies with kidney function or CKD. This primer summarizes the basic concepts of MR studies, highlighting methods used in recent applications, and emphasizes key elements in conducting and reporting of MR studies that are important for interpreting the results.

A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor

Ricaurte Archila, Luisa — Fri, 18 Jun 2021 11:02:43 GMT-07:00

Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure during Pregnancy: Role in Gestational Hypertension

jwei@usf.edu — Mon, 14 Jun 2021 11:36:35 GMT-07:00

Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice

ckurts@web.de — Fri, 18 Jun 2021 11:02:42 GMT-07:00

The Prognostic Significance of Body Mass Index and Metabolic Parameter Variabilities in Predialysis CKD: A Nationwide Observational Cohort Study

Park, Sehoon — Thu, 12 Aug 2021 09:53:45 GMT-07:00

Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice

hutchenm@ohsu.edu — Mon, 02 Aug 2021 09:41:21 GMT-07:00

Using both the Fraction and Quantity of Donor-Derived Cell-Free DNA to Detect Kidney Allograft Rejection

Bunnapradist, Suphamai — Wed, 23 Jun 2021 11:32:46 GMT-07:00

Renal Nerve Ablation in Nephritis and Beyond

roland.veelken@uk-erlangen.de — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKD

Danziger, John — Thu, 15 Jul 2021 01:18:28 GMT-07:00

MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesis

zhaobinghai01@vip.163.com — Fri, 03 Sep 2021 09:49:58 GMT-07:00

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children

Greenberg, Jason H. — Mon, 20 Sep 2021 10:39:42 GMT-07:00

Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial

Ravani, Pietro — Mon, 20 Sep 2021 10:39:41 GMT-07:00

Kim-1 Targeted Extracellular Vesicles: A New Therapeutic Platform for RNAi to Treat AKI

Tang, Tao-Tao — Mon, 14 Jun 2021 11:36:35 GMT-07:00

Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of Glucose

r.t.krediet@amsterdamumc.nl — Wed, 28 Jul 2021 09:47:04 GMT-07:00

Ultrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency—preferably called ultrafiltration failure—an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD+ ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, and the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality, long-term PD.

Authors’ Reply

Robinson, Cal H. — Thu, 16 Sep 2021 01:36:25 GMT-07:00

High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome

Caceres, Paulo S. — Fri, 04 Jun 2021 11:03:04 GMT-07:00

Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis

Anand, Shuchi — Fri, 11 Jun 2021 06:31:07 GMT-07:00

Pediatric Acute Kidney Injury Survivors Need Risk Stratification and Individualized Follow-Up

Zhao, Yuliang — Thu, 16 Sep 2021 01:36:25 GMT-07:00

Patient Health Outcomes following Dialysis Facility Closures in the United States

Niu, Jingbo — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis

Lu, Yueh-An — Mon, 21 Jun 2021 09:55:14 GMT-07:00

Correction: Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy

American Society of Nephrology — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes

Mychaleckyj, Josyf C. — Wed, 14 Jul 2021 09:30:46 GMT-07:00

Coding Variants in Susceptibility to Diabetic Kidney Disease

Liu, Lili — Fri, 01 Oct 2021 10:51:44 GMT-07:00

Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review

Mohottige, Dinushika — Fri, 09 Jul 2021 09:29:49 GMT-07:00

Due to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients’ quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.

Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: PRO

Devabhaktuni, Subodh R. — Fri, 09 Apr 2021 09:22:47 GMT-07:00

Renal Sensing of Bacterial Metabolites in the Gut-kidney Axis

Foresto-Neto, Orestes — Fri, 02 Jul 2021 11:27:00 GMT-07:00

Seminal works have now revealed the gut microbiota is connected with several diseases, including renal disorders. The balance between optimal and dysregulated host-microbiota interactions has completely changed our understanding of immunity and inflammation. Kidney injury is associated with accumulation of uremic toxins in the intestine, augmented intestinal permeability, and systemic inflammation. Intestinal bacteria can signal through innate receptors and induce immune cell activation in the lamina propria and release of inflammatory mediators into the bloodstream . But the gut microbiota can also modulate immune functions through soluble products as short-chain fatty acids (SCFAs). The three most common SCFAs are propionate, butyrate, and acetate, which can signal through specific G-protein coupled receptors (GPCRs), such as GPR43, GPR41, and GPR109a, expressed on the surface of epithelial, myeloid, endothelial, and immune cells, among others. The triggered signaling can change cell metabolism, immune cell activation, and cell death. In this study, we reviewed the gut-kidney axis, how kidney cells can sense SCFAs, and its implication in kidney diseases.

Collagen Remodeling Biomarkers in Lupus Nephritis

Caster, Dawn J. — Thu, 30 Sep 2021 05:30:25 GMT-07:00

Peroxisomal L-bifunctional Protein Deficiency Causes Male-specific Kidney Hypertrophy and Proximal Tubular Injury in Mice

Ranea-Robles, Pablo — Wed, 30 Jun 2021 01:27:41 GMT-07:00

Frailty, Age, and Postdialysis Recovery Time in a Population New to Hemodialysis

Fitzpatrick, Jessica — Tue, 13 Jul 2021 07:36:55 GMT-07:00

Tribute to Barbara Murphy

Coca, Steven G. — Fri, 06 Aug 2021 05:55:47 GMT-07:00

Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease

Arroyo, Juan Pablo — Thu, 08 Jul 2021 10:20:23 GMT-07:00

From Dropsy to Chart Biopsy: Opportunities and Pitfalls of Electronic Health Records

Cervantes, C. Elena — Thu, 30 Sep 2021 05:30:25 GMT-07:00

The Evaluation of Kidney Function in Living Kidney Donor Candidates

Garg, Neetika — Thu, 01 Jul 2021 09:38:52 GMT-07:00

Living kidney donors incur a small increased risk of ESKD, of which predonation GFR is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment, including eGFR, creatinine clearance, and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. eGFR obtained using the 2009 CKD Epidemiology Collaboration equation that, although the best of estimating estimations, tends to underestimate levels and has limited accuracy, especially near-normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of the evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics, depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of <60 ml/min per 1.73m2 for exclusion and ≥90 ml/min per 1.73m2 for acceptance, and determination of candidacy with intermediate GFR on the basis of long-term ESKD risk. However, several concerns exist for this strategy, including inappropriate acceptance of younger candidates due to underestimation of risk, and exclusion of older candidates whose kidney function is in fact appropriate for age. The role of cystatin C and other newer biomarkers, and data on the effect of predonation GFR on not just ESKD risk, but also advanced CKD risk and cardiovascular outcomes are needed.

Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in Denmark

Vestergaard, Søren Viborg — Thu, 03 Jun 2021 11:46:41 GMT-07:00

Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: COMMENTARY

Mavrakanas, Thomas A. — Fri, 09 Apr 2021 09:22:47 GMT-07:00

Unilateral Pleural Effusion in a Hemodialysis Patient

Spithoven, Edwin M. — Thu, 30 Sep 2021 05:30:25 GMT-07:00

Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia

Alrahmani, Layan — Wed, 30 Jun 2021 11:45:12 GMT-07:00

Collagen Type III and VI Remodeling Biomarkers Are Associated with Kidney Fibrosis in Lupus Nephritis

Genovese, Federica — Fri, 18 Jun 2021 11:50:07 GMT-07:00

Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day

Tandukar, Srijan — Thu, 08 Jul 2021 10:20:23 GMT-07:00

Post-Discharge Mortality and Rehospitalization among Participants in a Comprehensive Acute Kidney Injury Rehabilitation Program

Singh, Gurmukteshwar — Tue, 13 Jul 2021 11:42:24 GMT-07:00

Novel Uses of Ultrasound to Assess Kidney Mechanical Properties

Urban, Matthew W. — Thu, 01 Jul 2021 09:38:52 GMT-07:00

Ultrasound is a key imaging tool for evaluating the kidney. Over the last two decades, methods to measure the mechanical properties of soft tissues have been developed and used in clinical practice, although use in the kidney has not been as widespread as for other applications. The mechanical properties of the kidney are determined by the structure and composition of the renal parenchyma and perfusion characteristics. Because pathologic processes change these factors, the mechanical properties change and can be used for diagnostic purposes and for monitoring treatment or disease progression. Ultrasound-based elastography methods for evaluating the mechanical properties of the kidney use focused ultrasound beams to perturb the kidney and then high frame-rate ultrasound methods are used to measure the resulting motion. The motion is analyzed to estimate the mechanical properties. This review will describe the principles of these methods and discuss several seminal studies related to characterizing the kidney. Additionally, an overview of the clinical use of elastography methods in native and kidney allografts will be provided. Perspectives on future developments and uses of elastography technology along with other complementary ultrasound imaging modalities will be provided.

Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: CON

Lidgard, Benjamin — Fri, 09 Apr 2021 09:22:47 GMT-07:00

An Unexpected Kidney Biopsy Finding in a Patient with Newly Diagnosed SLE

Crane, Clarkson R. — Thu, 30 Sep 2021 05:30:25 GMT-07:00

An Unusual Cause of Peritoneal Dialysis Catheter Dysfunction

Sundararajan, Anusha — Thu, 30 Sep 2021 05:30:25 GMT-07:00

SARS-CoV-2 Vaccination: The Time Is Now

Wiegel, Joshua J. — Thu, 30 Sep 2021 05:30:25 GMT-07:00

Impaired Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients and in Kidney Transplant Recipients

Kolb, Thilo — Tue, 13 Jul 2021 06:19:55 GMT-07:00

Assessment of Acid-Base Status

Kraut, Jeffrey A. — Fri, 04 Jun 2021 11:54:31 GMT-07:00

Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation

Abramson, Matthew H. — Wed, 16 Jun 2021 10:53:39 GMT-07:00

Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance

Kaufman, Dixon B. — Wed, 07 Jul 2021 11:09:02 GMT-07:00

Evaluation of PROMIS Preference Scoring System (PROPr) in Patients Undergoing Hemodialysis or Kidney Transplant

Zhang, Jing — Fri, 16 Jul 2021 10:13:47 GMT-07:00

Reappraisal of Hemodiafiltration for Managing Uremic Complications

Grooteman, Muriel — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Fatigue in CKD

Gregg, L. Parker — Thu, 15 Apr 2021 06:45:48 GMT-07:00

Fatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD.

Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation

Thoreau, Benjamin — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor–Associated Adverse Events

Adam, Benjamin A. — Fri, 09 Jul 2021 06:46:32 GMT-07:00

Changing Demographics of NIDDK-Funded Physician-Scientists Doing Kidney Research

Abood, Delaney C. — Wed, 14 Jul 2021 09:12:42 GMT-07:00

Evolving Demographics of Nephrology Research Workforce in the United States

Quaggin, Susan E. — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney Disease

Ishida, Julie H. — Fri, 23 Apr 2021 09:43:33 GMT-07:00

Cardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%–60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.

Net Endogenous Acid Excretion and Kidney Allograft Outcomes

Yeung, Stanley M.H. — Wed, 16 Jun 2021 10:53:39 GMT-07:00

Gene Expression Profiling in Kidney Transplant Recipients on Immune Checkpoint Inhibitors

Jethwani, Priyanka — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Ertugliflozin and Slope of Chronic eGFR

Cherney, David Z.I. — Fri, 18 Jun 2021 10:59:27 GMT-07:00

The RALES Legacy and Finerenone Use on CKD Patients

Moura-Neto, José A. — Fri, 06 Aug 2021 09:21:35 GMT-07:00

Effect of Hemodiafiltration on the Progression of Neuropathy with Kidney Failure

Kang, Amy — Wed, 07 Jul 2021 11:09:02 GMT-07:00

Renal Denervation for the Treatment of Hypertension

Sarathy, Harini — Thu, 03 Jun 2021 10:41:09 GMT-07:00

An Apple a Day Keeps Dialysis Away

Stenson, Erin K. — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Are All SGLT2 Inhibitors Created Equal?

Gregg, L. Parker — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and CKD (AMBER)

Agarwal, Rajiv — Wed, 23 Jun 2021 10:54:11 GMT-07:00

COVID-19 among Adults Receiving Home versus In-Center Dialysis

Perl, Jeffrey — Fri, 04 Jun 2021 11:54:31 GMT-07:00

Patient Management When Returning to Dialysis after a Failed Kidney Transplant

Moist, Louise M. — Thu, 15 Apr 2021 06:45:49 GMT-07:00

Developing Patient-Reported Outcome Measures that Can Improve Kidney Care

Hartwell, Lori — Wed, 08 Sep 2021 05:37:36 GMT-07:00

Beyond the Biopsy: Monitoring Immune Status in Kidney Recipients

Bloom, Roy D. — Fri, 06 Aug 2021 09:21:35 GMT-07:00

Improved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.

Authors’ Reply

De Vriese, An S. — Wed, 18 Aug 2021 05:20:49 GMT-07:00

Self-Reported Medication Use and Urinary Drug Metabolites in the German Chronic Kidney Disease (GCKD) Study

Kotsis, Fruzsina — Thu, 17 Jun 2021 07:41:25 GMT-07:00

Novel Phenotypes for Acute Kidney Transplant Rejection Using Semi-Supervised Clustering

Matas, Arthur J. — Mon, 16 Aug 2021 06:09:49 GMT-07:00

The Bloody Mystery of Glomerular Tuft Development

Marciano, Denise K. — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and Cystogenesis

Hu, Chunyan — Thu, 27 May 2021 10:50:43 GMT-07:00

Authors’ Reply

Vaulet, Thibaut — Mon, 16 Aug 2021 06:09:49 GMT-07:00

Proteins Associated with Risk of Kidney Function Decline in the General Population

Grams, Morgan E. — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Recent Approaches to Targeting Canonical NFκB Signaling in the Early Inflammatory Response to Renal IRI

Reid, Shelby — Wed, 09 Jun 2021 10:56:04 GMT-07:00

Ischemia reperfusion injury (IRI) is the most common cause of in-hospital AKI and is associated with increased morbidity and mortality. IRI is associated with an early phase of inflammation primarily regulated by the canonical NFκB signaling pathway. Despite recent advances in our understanding of the pathogenesis of IRI, few therapeutic strategies have emerged. The purpose of this manuscript is to review interventions targeting NFκB after IRI.

This Month's Highlights

American Society of Nephrology — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Addressing Transplant Candidacy When Evaluating Safety of Direct Oral Anticoagulant Agents in Patients on Hemodialysis

Heher, Eliot — Wed, 18 Aug 2021 05:20:49 GMT-07:00

Comparative Health Care Spending for Dialysis: An Example of Public Cost Containment?

Tummalapalli, Sri Lekha — Mon, 16 Aug 2021 11:11:35 GMT-07:00

Prevalence Estimates of Predicted Pathogenic COL4A3–COL4A5 Variants in a Population Sequencing Database and Their Implications for Alport Syndrome

Gibson, Joel — Fri, 18 Jun 2021 11:02:43 GMT-07:00

Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome

Boudhabhay, Idris — Mon, 21 Jun 2021 09:55:14 GMT-07:00

High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients

Pfau, Anja — Mon, 19 Jul 2021 11:44:34 GMT-07:00

Barriers to Reducing Hemodialysis Time and Frequency in Patients with Residual Kidney Function

Meyer, Timothy W. — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Molecular Mechanisms of Renal Magnesium Reabsorption

Ellison, David H. — Thu, 27 May 2021 10:50:43 GMT-07:00

Magnesium is an essential cofactor in many cellular processes, and aberrations in magnesium homeostasis can have life-threatening consequences. The kidney plays a central role in maintaining serum magnesium within a narrow range (0.70–1.10 mmol/L). Along the proximal tubule and thick ascending limb, magnesium reabsorption occurs via paracellular pathways. Members of the claudin family form the magnesium pores in these segments, and also regulate magnesium reabsorption by adjusting the transepithelial voltage that drives it. Along the distal convoluted tubule transcellular reabsorption via heteromeric TRPM6/7 channels predominates, although paracellular reabsorption may also occur. In this segment, the NaCl cotransporter plays a critical role in determining transcellular magnesium reabsorption. Although the general machinery involved in renal magnesium reabsorption has been identified by studying genetic forms of magnesium imbalance, the mechanisms regulating it are poorly understood. This review discusses pathways of renal magnesium reabsorption by different segments of the nephron, emphasizing newer findings that provide insight into regulatory process, and outlining critical unanswered questions.

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney

Wu, Qi — Tue, 06 Jul 2021 10:49:17 GMT-07:00

Big Data and Glomerular Disease: Uncovering Common Outcomes of Rare Disease

Glenn, Dorey A. — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1–Deficient Polycystic Kidney Disease in Animal Model

He, Jinzhao — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development

Li, Jinyu — Mon, 02 Aug 2021 01:46:16 GMT-07:00

Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free Mice

Hatje, Favian A. — Tue, 01 Jun 2021 10:24:06 GMT-07:00

Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in Diabetes

Satake, Eiichiro — Thu, 17 Jun 2021 07:41:24 GMT-07:00

Predictors of Kidney Disease Progression in Diabetes and Precision Medicine: Something Old, Something New, and Something Borrowed

Vasquez-Rios, George — Tue, 31 Aug 2021 11:00:30 GMT-07:00

Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor Tissue

Dornieden, Theresa — Tue, 01 Jun 2021 12:21:07 GMT-07:00

Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study

Go, Alan S. — Fri, 18 Jun 2021 11:02:42 GMT-07:00

Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis Patients

Bertrand, Dominique — Thu, 10 Jun 2021 11:55:37 GMT-07:00

Humoral Response after SARS-CoV-2 mRNA Vaccination in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients

Danthu, Clément — Wed, 16 Jun 2021 10:31:16 GMT-07:00

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

Chertow, Glenn M. — Fri, 16 Jul 2021 10:14:04 GMT-07:00

Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions

Omer, Dorit — Thu, 10 Jun 2021 10:55:33 GMT-07:00

Dialysis and Total Health Care Costs in the United States and Worldwide: The Financial Impact of a Single-Payer Dominant System in the US

Pockros, Benjamin M. — Fri, 06 Aug 2021 09:22:04 GMT-07:00

Hemodialysis Patients Make Long-Lived Antibodies against SARS-CoV-2 that May Be Associated with Reduced Reinfection

Banham, Gemma D. — Mon, 02 Aug 2021 01:46:17 GMT-07:00

Racial Adjustment Adversely Affects Glomerular Filtration Estimates in Black Americans Living with HIV

Atta, Mohamed G. — Thu, 17 Jun 2021 07:41:25 GMT-07:00

Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?

Anpalahan, Aksharaa — Wed, 16 Jun 2021 09:35:00 GMT-07:00

Intimal Hyperplasia and Arteriovenous Fistula Failure: Looking Beyond Size Differences

Vazquez-Padron, Roberto I. — Thu, 03 Jun 2021 11:46:41 GMT-07:00

The development of venous intimal hyperplasia (IH) has been historically associated with failure of arteriovenous fistulas (AVFs) used for hemodialysis. This long-standing assumption, made on the basis of histologic observations, has been recently challenged by clinical studies indicating that the size of the intima by itself is not enough to explain stenosis or AVF maturation failure. Irrespective of this lack of association, IH is present in most native veins and fistulas, is prominent in many patients, and suggests a role in the vein that may not be reflected by its dimensions. Therefore, the contribution of IH to AVF dysfunction remains controversial. Using only clinical data and avoiding extrapolations from animal models, we critically discuss the biologic significance of IH in vein remodeling, vascular access function, and the response of the venous wall to repeated trauma in patients receiving hemodialysis. We address questions and pose new ones such as the following: What are the factors that contribute to IH in preaccess veins and AVFs? Do cellular phenotypes and composition of the intima influence AVF function? Are there protective roles of the venous intima? This review explores these possibilities, with hopes of rekindling a critical discussion about venous IH that goes beyond thickness and AVF outcomes.

Association of Blood Pressure Genetic Risk Score with Cardiovascular Disease and CKD Progression: Findings from the CRIC Study

Nierenberg, Jovia L. — Fri, 09 Apr 2021 06:02:57 GMT-07:00

New Frontiers in Vascular Access Practice: From Standardized to Patient-tailored Care and Shared Decision Making

Murea, Mariana — Tue, 15 Jun 2021 01:17:18 GMT-07:00

Vascular access planning is critical in the management of patients with advanced kidney disease who elect for hemodialysis for RRT. Policies put in place more than two decades ago attempted to standardize vascular access care around the model of optimal, namely arteriovenous fistula, and least preferred, namely central venous catheter, type of access. This homogenized approach to vascular access care emerged ineffective in the increasingly heterogeneous and complex dialysis population. The most recent vascular access guidelines acknowledge the limitations of standardized care and encourage tailoring vascular access care on the basis of patient and disease characteristics. In this article, we discuss available literature in support of patient-tailored access care on the basis of differences in vascular access outcomes by biologic and social factors—age, sex, and race. Further, we draw attention to the overlooked dimension of patient-reported preferences and shared decision making in the practice of vascular access planning. We discuss milestones to overcome as requisite steps to implement effective shared decision making in vascular access care. Finally, we take into consideration local practice cofactors as major players in vascular access fate. We conclude that a personalized approach to hemodialysis vascular access will require dynamic care specifically relevant to the individual on the basis of biologic factors, fluctuating clinical needs, values, and preferences.

Prevalence of Frailty in Patients Referred to the Kidney Transplant Waitlist

Worthen, George — Fri, 28 May 2021 06:11:29 GMT-07:00

The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular Mechanisms

Suzuki, Yusuke — Fri, 28 May 2021 07:45:33 GMT-07:00

IgA nephropathy (IgAn), defined by the pre dominant de position of IgA in the glomerular mesangium, is the most common form of GN throughout the world. However, its incidence, sex distribution, clinical presentation, and progression and pathogenic initiating factors are largely variable and do not fit such a simple definition. To assess the heterogeneity of this disease, we recently conducted a clinical survey on the presentation and clinical management of patients with IgAn in Europe and Japan. This clinical survey highlights similarities and differences in patients from different cont inents. The survey revealed obvious differences between nations in the frequency of gastrointestinal complications, including inflammatory bowel diseases (IBD) and celiac disease, which were more frequent in European patients. Such findings are compatible with susceptibility loci related to intestinal immunity and IBD in recent genome wide association studies (GWAS) on IgAn. However, most of the molecules in these mucosal-related loci fulfill the immunologic function not only of gut-associated lymphoid tissue (GALT), but also nasopharyngeal/bronchial-associated lymphoid tissues (NALT/BALT). Indeed, a similar frequency of macrohematuria coinciding with upper respiratory infection, a hallmark manifestation of this disease, was found in the survey, emphasizing the pathogenic roles of these molecules in the NALT/BALT of patients with IgAn. Recent experimental and clinical studies including GWAS on multiple common infections and IBD indicate immune crosstalk between GALT and NALT/BALT, and some related mediators, such as TNF superfamily ligands (APRIL/BAFF). This review explains the epidemiologic heterogeneity of this disease with the clinical survey, and discusses race and sex-dependent molecular mechanisms.

Novel Clinical Therapies and Technologies in Dialysis Vascular Access

Takahashi, Edwin A. — Thu, 10 Jun 2021 01:48:29 GMT-07:00

The hemodialysis population continues to grow. Although procedures for dialysis have existed for >60 years, significant challenges with vascular access to support hemodialysis persist. Failure of arteriovenous fistulas (AVFs) to mature, loss of AVF and graft patency, thrombosis, and infection hinder long-term access, and add extra health care costs and patient morbidity. There have been numerous innovations over the last decade aimed at addressing the issues. In this study, we review the literature and summarize the recent evolution of drug delivery, graft development, minimally invasive AVF creation, and stem-cell therapy for hemodialysis access.

New Vancomycin Dosing Guidelines for Hemodialysis Patients: Rationale, Caveats, and Limitations

Lewis, Susan J. — Fri, 21 May 2021 01:33:40 GMT-07:00

Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease

Strohbehn, Ian A. — Fri, 21 May 2021 11:34:27 GMT-07:00

Through the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.

Unusual Kidney Findings in a Patient with Abdominal Pain and Kidney Dysfunction

Ferreira, Filipa — Thu, 26 Aug 2021 05:30:24 GMT-07:00

Use of Ultrasound to Assess Hemodynamics in Acutely Ill Patients

Safadi, Sami — Wed, 02 Jun 2021 12:53:39 GMT-07:00

Early diagnosis of AKI and preventive measures can likely decrease the severity of the injury and improve patient outcomes. Current hemodynamic monitoring variables, including BP, heart and respiratory rates, temperature, and oxygenation status, have been used to identify patients at high risk for AKI. Despite the widespread use of such variables, their ability to accurately and timely detect patients who are high risk has been questioned. Therefore, there is a critical need to develop and validate tools that can measure new and more kidney-specific hemodynamic and laboratory variables, potentially assisting with AKI risk stratification, implementing appropriate and timely preventive measures, and hopefully improved outcomes. The new ultrasonography techniques provide novel insights into kidney hemodynamics and potential management and/or therapeutic targets. Contrast-enhanced ultrasonography; Doppler flow patterns of hepatic veins, portal vein, and intrakidney veins; and ultrasound elastography are among approaches that may provide such information, particularly related to vascular changes in AKI, venous volume excess or congestion, and fluid tolerance. This review summarizes the current state of these techniques and their relevance to kidney hemodynamic management.

Transforming Growth Factor Beta Receptor 3 (TGFBR3)–Associated Membranous Nephropathy

Caza, Tiffany N. — Fri, 11 Jun 2021 11:47:29 GMT-07:00

Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease

Martin, William P. — Fri, 21 May 2021 08:25:58 GMT-07:00

Comprehensive Assessment of Fluid Status by Point-of-Care Ultrasonography

Argaiz, Eduardo R. — Fri, 28 May 2021 06:11:29 GMT-07:00

The management of complex fluid and electrolyte disorders is central to the practice of nephrologists. The sensitivity of physical examination alone to determine fluid status is limited, precluding accurate clinical decision making. Point-of-care ultrasonography (POCUS) is emerging as a valuable, noninvasive, bedside diagnostic tool for objective evaluation of physiologic and hemodynamic parameters related to fluid status, tolerance, and responsiveness. Rapid bedside sonographic evaluation can obtain qualitative data on cardiac function and quantitative data on pulmonary congestion. Advanced POCUS, including goal-directed Doppler echocardiography, provides additional quantitative information, including flow velocities and pressures across the cardiac structures. Recently, abnormal Doppler flow patterns in abdominal organs secondary to increased right atrial pressure have been linked to congestive organ damage, adding another component to the hemodynamic assessment. Integrating POCUS findings with clinical and laboratory data can further elucidate a patient’s hemodynamic status. This drives decisions regarding crystalloid administration or, conversely, diuresis or ultrafiltration and allows tailored therapy for individual patients. In this article, we provide an overview of the focused assessment of cardiovascular function and pulmonary and venous congestion using POCUS and review relevant literature.

Nodular Lesions on the Hands of an ESKD Patient on Hemodialysis

Fung, Winston Wing Shing — Thu, 26 Aug 2021 05:30:24 GMT-07:00

Genetic Risk Scores and Blood Pressure — The Heart is What Matters

Boumitri, Mirna — Thu, 26 Aug 2021 05:30:24 GMT-07:00

A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled Trial

Bakris, George L. — Wed, 30 Jun 2021 11:45:12 GMT-07:00

Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study

Malik, Rubab F. — Thu, 03 Jun 2021 06:17:21 GMT-07:00

New Onset Diabetes Mellitus after Transplant: The Challenge Continues

Aziz, Fahad — Thu, 26 Aug 2021 05:30:24 GMT-07:00

Association of AKI-D with Urinary Findings and Baseline eGFR in Hospitalized COVID-19 Patients

Patel, Dipal M. — Thu, 20 May 2021 11:51:54 GMT-07:00

The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls

Shah, Neal B. — Wed, 09 Jun 2021 01:36:50 GMT-07:00

Introduction to Kidney Transplantation: Long-Term Management Challenges

Sawinski, Deirdre — Wed, 10 Mar 2021 09:39:07 GMT-08:00

Metabolite Biomarkers of CKD Progression in Children

Denburg, Michelle R. — Fri, 06 Aug 2021 11:00:21 GMT-07:00

The Promise of Metabolomics in Decelerating CKD Progression in Children

Schultheiss, Ulla T. — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy

Palmer, Biff F. — Tue, 09 Feb 2021 06:53:45 GMT-08:00

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na+-glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na+ or K+ salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.

Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patients

b.caplin@ucl.ac.uk — Tue, 01 Jun 2021 10:26:55 GMT-07:00

Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 Therapy

Schmidt, Julius J. — Fri, 23 Jul 2021 02:15:11 GMT-07:00

Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19

Chan, Lili — Mon, 24 May 2021 02:37:49 GMT-07:00

Evidence-Based Practices to Reduce COVID-19 Transmission in Dialysis Facilities

Kliger, Alan S. — Wed, 04 Aug 2021 06:10:08 GMT-07:00

Predictive Approaches for Acute Dialysis Requirement and Death in COVID-19

Vaid, Akhil — Mon, 24 May 2021 02:37:49 GMT-07:00

A Case of Focal Segmental Glomerulosclerosis

Hogan, Jonathan J. — Tue, 09 Mar 2021 06:42:55 GMT-08:00

Keeping Dialysis Patients Safe

Wager, Roberta L. — Wed, 04 Aug 2021 06:10:08 GMT-07:00

Long-Term Immunosuppression Management

Wojciechowski, David — Wed, 14 Apr 2021 06:10:56 GMT-07:00

The long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5–8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor–based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.

Virtual Interviews for Nephrology Fellowship Candidates

Farouk, Samira S. — Tue, 15 Jun 2021 11:37:17 GMT-07:00

Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation

Heerspink, Hiddo J. L. — Tue, 20 Apr 2021 11:01:49 GMT-07:00

Prioritizing Peritoneal Catheter Placement during the COVID-19 Pandemic

Oliver, Matthew J. — Fri, 12 Mar 2021 06:08:00 GMT-08:00

HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy

Le, Wei-Bo — Thu, 03 Jun 2021 10:41:09 GMT-07:00

Cardiovascular Safety of Roxadustat in CKD Anemia

Winkelmayer, Wolfgang C. — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Latency, Anti-Bacterial Resistance Pattern, and Bacterial Infection–Related Glomerulonephritis

John, Elenjickal Elias — Mon, 07 Jun 2021 11:50:50 GMT-07:00

Temporal Trends of Acute Kidney Injury and Associated Risk Exposures in Extremely Preterm Infants

huangped@mail.ncku.edu.tw — Wed, 04 Aug 2021 07:07:05 GMT-07:00

The Continuum of Acid Stress

Wesson, Donald E. — Fri, 19 Mar 2021 07:37:54 GMT-07:00

Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This “acid stress” continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.

The Effects of Oral Energy-Dense Supplements on Nutritional Status in Nondiabetic Maintenance Hemodialysis Patients

Yang, Yaya — Mon, 21 Jun 2021 09:54:33 GMT-07:00

Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes

Kim, Sun H. — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Correction: Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies: A French Nationwide Cohort Study

American Society of Nephrology — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non–Dialysis-Dependent CKD

Provenzano, Robert — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Better Nutrition Care for Patients on Hemodialysis

Ikizler, T. Alp — Wed, 04 Aug 2021 08:03:44 GMT-07:00

New Insights into Epidemiology and Outcome of Bacterial Infection–Related Glomerulonephritis

Medjeral-Thomas, Nicholas R. — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults

Uffing, Audrey — Fri, 06 Aug 2021 11:00:21 GMT-07:00

Transplant Biopsy Assessment in 21st Century

Malone, Andrew F. — Mon, 19 Jul 2021 01:48:31 GMT-07:00

Biobanks Linked to Electronic Health Records Accelerate Genomic Discovery

Crawford, Dana C. — Fri, 09 Jul 2021 06:39:02 GMT-07:00

Data-Driven Kidney Transplant Phenotyping as a Histology-Independent Framework for Biomarker Discovery

Buscher, Konrad — Wed, 02 Jun 2021 11:42:25 GMT-07:00

Prevention of Post-Transplantation Diabetes: Small Steps, Big Opportunities

Sharif, Adnan — Fri, 30 Jul 2021 11:00:32 GMT-07:00

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial

Schwaiger, Elisabeth — Fri, 30 Jul 2021 11:00:32 GMT-07:00

Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing Kidney

Makayes, Yaniv — Thu, 06 May 2021 05:18:48 GMT-07:00

Long-Term Kidney Outcomes Following Dialysis-Treated Childhood Acute Kidney Injury: A Population-Based Cohort Study

Robinson, Cal H. — Wed, 26 May 2021 12:00:54 GMT-07:00

Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York City

Tummalapalli, Sri Lekha — Thu, 03 Jun 2021 10:55:07 GMT-07:00

Procurement Biopsies in Kidney Transplantation: More Information May Not Lead to Better Decisions

Lentine, Krista L. — Thu, 27 May 2021 10:50:43 GMT-07:00

Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic Dialysis

Cohen, Dena E. — Fri, 02 Jul 2021 08:30:07 GMT-07:00

A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans

Dai, Lei — Fri, 28 May 2021 10:31:36 GMT-07:00

Presence of SARS-CoV-2 Antibodies in Spent Peritoneal Dialysate

Wang, Xiaoling — Tue, 06 Jul 2021 11:35:56 GMT-07:00

Race-Free Equations for eGFR: Comparing Effects on CKD Classification

Diao, James A. — Thu, 29 Jul 2021 01:47:08 GMT-07:00

Considerations in Comparing Proximal Tubule Cell Culture Models

Weisz, Ora A. — Mon, 12 Jul 2021 04:19:15 GMT-07:00

Correction: Long-Term Exposure to Ambient PM2.5 and Increased Risk of Chronic Kidney Disease Prevalence in China

American Society of Nephrology — Thu, 17 Jun 2021 07:41:24 GMT-07:00

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer

Stremke, Elizabeth R. — Thu, 08 Jul 2021 08:10:52 GMT-07:00

Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney Disease

Kritmetapak, Kittrawee — Fri, 30 Jul 2021 11:00:32 GMT-07:00

Missing Self–Induced Microvascular Rejection of Kidney Allografts: A Population-Based Study

Callemeyn, Jasper — Thu, 22 Jul 2021 06:31:45 GMT-07:00

Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration Barrier

Zhang, Haijiao — Fri, 30 Jul 2021 11:00:32 GMT-07:00

TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Cordido, Adrian — Mon, 21 Jun 2021 09:55:14 GMT-07:00

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia

Guedes, Murilo — Thu, 08 Jul 2021 08:10:52 GMT-07:00

Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease

dborza@mmc.edu — Fri, 23 Apr 2021 09:46:52 GMT-07:00

REST and Stress Resistance in the Aging Kidney

Magassa, Sato — Wed, 02 Jun 2021 11:22:10 GMT-07:00

Circulating Soluble Fms-like Tyrosine Kinase in Renal Diseases Other than Preeclampsia

giodimarco@gmail.com — Mon, 21 Jun 2021 09:55:14 GMT-07:00

Soluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.

Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model

Takemon, Yuka — Thu, 27 May 2021 10:50:43 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 30 Jul 2021 11:00:32 GMT-07:00

Medical Records-Based Genetic Studies of the Complement System

kk473@columbia.edu — Mon, 03 May 2021 06:08:23 GMT-07:00

Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy

Kim, Seo Rin — Wed, 16 Jun 2021 10:31:16 GMT-07:00

Current Methodological Challenges of Single-Cell and Single-Nucleus RNA-Sequencing in Glomerular Diseases

ben.sprangers@uzleuven.be — Thu, 17 Jun 2021 07:41:25 GMT-07:00

Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.

Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic

Moses, Andrew A. — Fri, 14 May 2021 11:46:11 GMT-07:00

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and—therefore—safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.

Living Organ Donor Hesitancy about COVID-19 Vaccines: A New Kind of “Source Control Issue”

Jorgenson, Margaret R. — Thu, 29 Jul 2021 05:30:28 GMT-07:00

Expression of ACE2 in the Intact and Acutely Injured Kidney

Nath, Karl A. — Tue, 18 May 2021 01:29:37 GMT-07:00

Risks and Benefits of Kidney Transplantation during the COVID-19 Pandemic: Transplant or Not Transplant?

Ajaimy, Maria — Thu, 13 May 2021 05:57:09 GMT-07:00

COVID-19 has significantly affected the transplant community, by leading to decreased transplant activity and increased waiting list time. As expected, COVID-19 causes substantial mortality in both ESKD and kidney transplant populations. This is due to underlying CKD and a high prevalence of comorbid conditions, such as diabetes mellitus, hypertension, and cardiovascular disease in this group. Transplant programs have faced the difficult decision of weighing the risks and benefits of transplantation during the pandemic. On one hand, there is a risk of COVID-19 exposure leading to infection while patients are on maximum immunosuppression. Alternatively, there are risks of delaying transplantation, which will increase waitlist times and may lead to waitlist-associated morbidity and mortality. Cautious and thoughtful selection of both the recipient’s and donor’s post-transplant management has been required during the pandemic, to mitigate the risk of morbidity and mortality associated with COVID-19. In this review article, we aimed to discuss previous publications related to clinical outcomes of COVID-19 disease in kidney transplant recipients, patients with ESKD on dialysis, or on the transplant waiting list, and the precautions transplant centers should take in decision making for recipient and donor selection and immunosuppressive management during the pandemic. Nevertheless, transplantation in this milieu does seem to be the correct decision, with careful patient and donor selection and safeguard protocols for infection prevention. Each center should conduct risk assessment on the basis of the patient’s age and medical comorbidities, waitlist time, degree of sensitization, cold ischemia time, status of vaccination, and severity of pandemic in their region.

Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness

Stevens, Jacob S. — Mon, 17 May 2021 01:38:21 GMT-07:00

Living Organ Donor Perspectives and Sources of Hesitancy about COVID-19 Vaccines

Harhay, Meera N. — Thu, 22 Apr 2021 01:34:55 GMT-07:00

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19

Khatri, Minesh — Thu, 06 May 2021 01:38:52 GMT-07:00

Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: COMMENTARY

Campbell, Kirk N. — Fri, 05 Feb 2021 01:36:13 GMT-08:00

Corticosteroids Should Be Used To Treat Slowly Progressive IgA Nephropathy: PRO

Cunningham, Amanda M. — Fri, 05 Feb 2021 03:31:07 GMT-08:00

Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: CON

Barratt, Jonathan — Fri, 05 Feb 2021 02:06:35 GMT-08:00

Confounding in Observational Studies Evaluating the Safety and Effectiveness of Medical Treatments

Assimon, Magdalene M. — Fri, 14 May 2021 09:25:02 GMT-07:00

Global Perspective on Kidney Transplantation: Thailand

Larpparisuth, Nuttasith — Fri, 14 May 2021 09:25:02 GMT-07:00

Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For?

Patel, Niralee — Thu, 22 Apr 2021 01:34:55 GMT-07:00

Global Perspective on Kidney Transplantation: Turkey

Andacoglu, Oya — Wed, 12 May 2021 11:39:45 GMT-07:00

A Perspective on the Metabolic Potential for Microbial Contributions to Urolithiasis

Agudelo, Jose — Thu, 22 Apr 2021 08:00:35 GMT-07:00

Strategies for Continuous Renal Replacement Therapy De-escalation

Gautam, Samir C. — Thu, 15 Apr 2021 11:38:16 GMT-07:00

Improving Clearance for Renal Replacement Therapy

Lee, Seolhyun — Wed, 12 May 2021 11:39:45 GMT-07:00

The adequacy of hemodialysis is now assessed by measuring the removal of a single solute, urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and, therefore, cannot be increased much further. However, other solutes, which are less effectively cleared than urea, may contribute more to the residual uremic illness suffered by patients on hemodialysis. Here, we review a variety of methods that could be used to increase the clearance of such nonurea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients’ health.

G protein- and β-arrestin Signaling Profiles of Endothelin Derivatives at the Type A Endothelin Receptor

Xiong, Xinyu — Mon, 17 May 2021 01:38:21 GMT-07:00

An Unusual Cause of Kidney Allograft Dysfunction

Rosenstiel, Paul E. — Thu, 29 Jul 2021 05:30:28 GMT-07:00

Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease

Akihisa, Taro — Tue, 18 May 2021 01:29:37 GMT-07:00

Single Cell Technologies: Beyond Microfluidics

Li, Haikuo — Fri, 14 May 2021 09:25:02 GMT-07:00

Single-cell RNA-sequencing (scRNA-seq) has been widely adopted in recent years due to standardized protocols and automation, reliability, and standardized bioinformatic pipelines. The most widely adopted platform is the 10× Genomics solution. Although powerful, this system is limited by its high cost, moderate throughput, and the inability to customize due to fixed kit components. This study will cover new approaches that do not rely on microfluidics and thus have low entry costs, are highly customizable, and are within the reach of any laboratory possessing molecular biology expertise.

Stakeholder-Guided Development of Dialysis Vascular Access Education Materials

Dorough, Adeline — Mon, 03 May 2021 07:24:05 GMT-07:00

An Atypical Kidney-Related Presentation of Multiple Myeloma

Muniz, Monique Pereira Rêgo — Thu, 29 Jul 2021 05:30:28 GMT-07:00

Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study

Salehi, Tania — Tue, 18 May 2021 01:29:37 GMT-07:00

Kidney Disease Burden and Kidney Transplantation: A True Story

Rodriguez, David — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Over Four Decades of Life with Dialysis: A Tale of Self-Empowerment

Strauss, Franklin G. — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Mixed Methods Research To Advance Nephrology

Wong, Susan P. Y. — Wed, 17 Mar 2021 01:22:31 GMT-07:00

eGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare Reimagined

Meraz-Muñoz, Alejandro Y. — Fri, 26 Mar 2021 07:32:10 GMT-07:00

Global Dialysis Perspective: Mauritius

Ip Min Wan, Davy — Fri, 26 Mar 2021 12:18:40 GMT-07:00

Global Dialysis Perspective: Kuwait

AlSahow, Ali — Wed, 07 Apr 2021 01:28:30 GMT-07:00

Payment, Coverage, and Health Economics of SGLT2 Inhibitors

Pham, Ngoc-Yen T. — Thu, 18 Mar 2021 09:25:01 GMT-07:00

The Challenges of Acute Interstitial Nephritis: Time to Standardize

Moledina, Dennis G. — Thu, 01 Apr 2021 01:28:36 GMT-07:00

Examining the Role of Novel CKD Therapies for the ADPKD Patient

Patel, Dipal M. — Wed, 24 Mar 2021 09:49:59 GMT-07:00

Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients

George, Santosh — Wed, 14 Apr 2021 11:50:46 GMT-07:00

Ly6chi Infiltrating Macrophages Promote Cyst Progression in Injured Conditional Ift88 Mice

Aloria, Ernald Jules G. — Wed, 28 Apr 2021 12:29:36 GMT-07:00

Late Relapses of Membranous Nephropathy: A Case Series

Peleg, Yonatan — Wed, 28 Apr 2021 07:54:54 GMT-07:00

Glucocorticoid Therapy in ANCA Vasculitis: Using the Glucocorticoid Toxicity Index as an Outcome Measure

Floyd, Lauren — Tue, 20 Apr 2021 12:33:13 GMT-07:00

Evaluation of Suspected Outflow Stenosis in an Aneurysmal AVF

Sharma, Mukesh K. — Tue, 13 Jul 2021 06:20:42 GMT-07:00

Evolution of Vascular Access Use among Incident Patients during the First Year on Hemodialysis: A National Cohort Study

Hussein, Wael F. — Thu, 22 Apr 2021 09:59:21 GMT-07:00

Implementation of Surprise Question Assessments using the Electronic Health Record in Older Adults with Advanced CKD

Ernecoff, Natalie C. — Thu, 01 Apr 2021 09:33:58 GMT-07:00

Patient-Reported Experiences with Dialysis Care and Provider Visit Frequency

kevin.erickson@bcm.edu — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Dialysis-Associated Neurovascular Injury (DANI) in Acute Brain Injury

Ghoshal, Shivani — Thu, 11 Feb 2021 11:46:09 GMT-08:00

The Patient Voice in Health Care Decision Making

Sadusky, Tami — Tue, 09 Mar 2021 06:42:55 GMT-08:00

Racial Health Inequities and Clinical Algorithms

Neal, Richard E. — Fri, 05 Mar 2021 02:00:07 GMT-08:00

Slowing Progression in CKD

Larmour, Kathryn — Wed, 10 Mar 2021 08:09:01 GMT-08:00

Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood

Calatroni, Marta — Wed, 26 May 2021 10:45:44 GMT-07:00

Genetic Basis of Type IV Collagen Disorders of the Kidney

Quinlan, Catherine — Tue, 13 Apr 2021 08:05:32 GMT-07:00

The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.

Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1

Frishberg, Yaacov — Thu, 13 May 2021 06:13:18 GMT-07:00

Shining More Light on RAS Inhibition during the COVID-19 Pandemic

Rianto, Fitra — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Renin-Angiotensin System Blockers and the Risk of COVID-19–Related Mortality in Patients with Kidney Failure

Soler, Maria Jose — Fri, 04 Jun 2021 11:54:31 GMT-07:00

Balancing the Needs of Acute and Maintenance Dialysis Patients during the COVID-19 Pandemic

Carson, Rachel C. — Mon, 08 Feb 2021 09:47:52 GMT-08:00

The COVID-19 pandemic continues to strain health care systems and drive shortages in medical supplies and equipment around the world. Resource allocation in times of scarcity requires transparent, ethical frameworks to optimize decision making and reduce health care worker and patient distress. The complexity of allocating dialysis resources for both patients receiving acute and maintenance dialysis has not previously been addressed. Using a rapid, collaborative, and iterative process, BC Renal, a provincial network in Canada, engaged patients, doctors, ethicists, administrators, and nurses to develop a framework for addressing system capacity, communication challenges, and allocation decisions. The guiding ethical principles that underpin this framework are (1) maximizing benefits, (2) treating people fairly, (3) prioritizing the worst-off individuals, and (4) procedural justice. Algorithms to support resource allocation and triage of patients were tested using simulations, and the final framework was reviewed and endorsed by members of the provincial nephrology community. The unique aspects of this allocation framework are the consideration of two diverse patient groups who require dialysis (acute and maintenance), and the application of two allocation criteria (urgency and prognosis) to each group in a sequential matrix. We acknowledge the context of the Canadian health care system, and a universal payer in which this framework was developed. The intention is to promote fair decision making and to maintain an equitable reallocation of limited resources for a complex problem during a pandemic.

Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b2

Speer, Claudius — Mon, 24 May 2021 02:37:49 GMT-07:00

Prevalence of SARS-CoV-2-IgG Antibodies in Children with CKD or Immunosuppression

Morello, William — Mon, 07 Jun 2021 02:18:37 GMT-07:00

mRNA COVID-19 Vaccine for People with Kidney Failure: Hope but Prudence Warranted

Miskulin, Dana C. — Thu, 27 May 2021 09:25:51 GMT-07:00

Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis

Grupper, Ayelet — Tue, 06 Apr 2021 07:54:43 GMT-07:00

Nephrology—Taking the Lead

Agarwal, Anupam — Mon, 01 Mar 2021 06:01:34 GMT-08:00

Correction: Inherited Tubulopathies of the Kidney: Insights from Genetics

American Society of Nephrology — Thu, 27 May 2021 09:25:51 GMT-07:00

Kidney Disease Symptoms before and after Kidney Transplantation

mara@jhu.edu — Fri, 18 Jun 2021 10:59:27 GMT-07:00

Nephrologist Follow-Up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION): A Randomized Controlled Trial

Silver, Samuel A. — Fri, 21 May 2021 04:58:47 GMT-07:00

Planning Patient Care after Acute Kidney Injury: Not as Easy as It May Seem

Selby, Nicholas M. — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk of Abnormal Serum Potassium Level

Hwang, Y. Joseph — Mon, 12 Jul 2021 07:54:45 GMT-07:00

Management of Heart Failure Patient with CKD

Banerjee, Debasish — Mon, 25 Jan 2021 07:53:45 GMT-08:00

CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m2. Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.

Prediction of Incident Atrial Fibrillation in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Study

Zelnick, Leila R. — Mon, 12 Jul 2021 07:54:45 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Mon, 12 Jul 2021 06:29:52 GMT-07:00

The Sniffing Kidney: Roles for Renal Olfactory Receptors in Health and Disease

Shepard, Blythe D. — Mon, 19 Apr 2021 02:13:27 GMT-07:00

Olfactory receptors (ORs) represent the largest gene family in the human genome. Despite their name, functions exist for these receptors outside of the nose. Among the tissues known to take advantage of OR signaling is the kidney. From mouse to man, the list of renal ORs continues to expand, and they have now been linked to a variety of processes involved in the maintenance of renal homeostasis, including the modulation of blood pressure, response to acidemia, and the development of diabetes. In this review, we highlight the recent progress made on the growing appreciation for renal ORs in physiology and pathophysiology.

Global Dialysis Perspective: Brunei Darussalam

Lim, Chiao Yuen — Mon, 19 Apr 2021 02:13:27 GMT-07:00

Adding Life to Their Years: The Current State of Pediatric Palliative Care in CKD

House, Taylor R. — Wed, 07 Apr 2021 01:28:30 GMT-07:00

Despite continued advances in medical treatment, pediatric CKD remains an unremitting, burdensome condition characterized by decreased quality of life and earlier death. These burdens underscore the need for integration of pediatric palliative care (PPC) into nephrology practice. PPC is an evolving field that strives to (1) relieve physical, psychologic, social, practical, and existential suffering; (2) improve quality of life; (3) facilitate decision making; and (4) assist with care coordination in children with life-threatening or life-shortening conditions. Integration of palliative care into routine care has already begun for adults with kidney disease and children with other chronic diseases; however, similar integration has not occurred in pediatric nephrology. This review serves to provide a comprehensive definition of PPC, highlight the unmet need in pediatric nephrology and current integration efforts, discuss the state of palliative care in adult nephrology and analogous chronic pediatric disease states, and introduce future opportunities for study.

SARS-CoV-2 Infection Risk Factors among Maintenance Hemodialysis Patients and Health Care Personnel In Outpatient Hemodialysis Centers

Gandra, Sumanth — Wed, 21 Apr 2021 06:02:44 GMT-07:00

Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among Veterans

Cui, Xiangqin — Wed, 28 Apr 2021 12:29:36 GMT-07:00

Vaccine and the Need To Be Heard: Considerations for COVID-19 Immunization in ESKD

Srivatana, Vesh — Thu, 08 Apr 2021 01:50:57 GMT-07:00

Development and Validation of a Transfusion Risk Score for Patients Receiving Maintenance Hemodialysis

Gilbertson, David T. — Fri, 09 Apr 2021 08:03:38 GMT-07:00

Performance and Hemocompatibility of a Novel Polysulfone Dialyzer: A Randomized Controlled Trial

Ehlerding, Götz — Wed, 07 Apr 2021 01:28:30 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 02 Jul 2021 12:51:34 GMT-07:00

Identification of an Altered Matrix Signature in Kidney Aging and Disease

Randles, Michael J. — Fri, 28 May 2021 11:41:26 GMT-07:00

High Incidence of Circuit Clotting in Critically Ill COVID-19 Patients Treated with Renal Replacement Therapy

Grenon, Eloïse — Fri, 28 May 2021 10:31:36 GMT-07:00

Epidemiology and Outcomes of COVID-19 in Home Dialysis Patients Compared with In-Center Dialysis Patients

Hsu, Caroline M. — Wed, 09 Jun 2021 01:22:33 GMT-07:00

Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost Opportunities

Schold, Jesse D. — Thu, 17 Jun 2021 02:32:26 GMT-07:00

Diagnosis, Education, and Care of Patients with APOL1-Associated Nephropathy: A Delphi Consensus and Systematic Review

Freedman, Barry I. — Wed, 14 Apr 2021 08:05:58 GMT-07:00

Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure

Borges-Júnior, Flávio A. — Mon, 12 Apr 2021 08:29:15 GMT-07:00

New Kidney and Pancreas Allocation Policy: Moving to a Circle as the First Unit of Allocation

Israni, Ajay — Thu, 17 Jun 2021 01:44:29 GMT-07:00

SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey

Garcia, Pablo — Thu, 29 Apr 2021 04:53:52 GMT-07:00

Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy

Al-Rabadi, Laith Farah — Wed, 05 May 2021 11:31:21 GMT-07:00

Utility of Phosphate Binder Equivalent Dose Concept

Kulkarni, Manjunath — Wed, 30 Jun 2021 07:50:25 GMT-07:00

The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 Trial

Heida, Judith E. — Thu, 22 Apr 2021 09:57:01 GMT-07:00

Role of Platelets in Chronic Kidney Disease

Jain, Nishank — Thu, 17 Jun 2021 01:44:29 GMT-07:00

Platelet-dependent mechanisms for excessive clotting and bleeding in CKD remain undefined. Moreover, platelets’ contribution to inflammation, and specifically to CKD, are equally elusive. To date, descriptions of changes in the functional properties of circulating platelets during CKD have provided confusing interpretations. Experimental approaches that can advance our understanding of platelet dysfunction in CKD are needed, and studies that provide mechanistic insights into the dynamic relationships between thrombosis, bleeding, and inflammation associated with CKD will be essential to improve clinical management and outcomes for this vulnerable population. This article summarizes existing literature characterizing platelets in CKD and identifies areas that need further investigation.

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS

Lane, Brandon M. — Fri, 16 Apr 2021 06:48:33 GMT-07:00

Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized Trial

Tangri, Navdeep — Thu, 15 Apr 2021 06:16:02 GMT-07:00

Cardiac and Noncardiac Determinants of Exercise Capacity in CKD

Chinnappa, Shanmugakumar — Fri, 18 Jun 2021 11:02:43 GMT-07:00

Authors’ Reply

Pergola, Pablo E. — Wed, 30 Jun 2021 07:50:25 GMT-07:00

Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study

pamela.matias@helmholtz-muenchen.de — Wed, 16 Jun 2021 10:31:16 GMT-07:00

Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury

Hasegawa, Sho — Mon, 19 Apr 2021 08:55:47 GMT-07:00

Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD

Nangaku, Masaomi — Wed, 21 Apr 2021 06:27:51 GMT-07:00

Primacy in Kidney Allocation: Does It Alleviate the Barriers to Transplantation?

Gill, John S. — Thu, 17 Jun 2021 02:05:27 GMT-07:00

Autonomous Calcium Signaling in Human and Zebrafish Podocytes Controls Kidney Filtration Barrier Morphogenesis

Djenoune, Lydia — Wed, 28 Apr 2021 06:02:25 GMT-07:00

3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development

Lipp, Sarah N. — Mon, 19 Apr 2021 08:55:48 GMT-07:00

Platelet Function in CKD: A Systematic Review and Meta-Analysis

Baaten, Constance C.F.M.J. — Mon, 03 May 2021 06:08:23 GMT-07:00

Too Little or Too Much? Extracellular Matrix Remodeling in Kidney Health and Disease

Clotet-Freixas, Sergi — Wed, 16 Jun 2021 10:31:16 GMT-07:00

Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis

Sears, Sophia M. — Fri, 28 May 2021 10:31:36 GMT-07:00

The effectiveness of cisplatin, a mainstay in the treatment of many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI in 30% of patients. Patients who do not develop AKI by clinical standards during treatment are still at risk for long-term decline in kidney function and the development of CKD. The connection between AKI and CKD has become increasingly studied, with renal fibrosis a hallmark of CKD development. To prevent both the short- and long-term effects of cisplatin, researchers must use models that reflect both types of pathology. Although a lot is known about cisplatin-induced AKI, very little is known about the mechanisms by which repeated low levels of cisplatin lead to fibrosis development. In this review, strategies used in various rodent models to prevent kidney injury, its progression to fibrosis, or both, are examined to gain mechanistic insights and identify potential therapeutic targets for cisplatin-induced kidney pathologies. Reviewing the results from these models highlights the diverse and highly complex role of cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation in acute and chronic kidney injuries. The use of several models of kidney injury is needed for development of agents that will prevent all aspects of cisplatin-induced kidney injury.

Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model

Misra, Sanjay — Fri, 23 Apr 2021 09:46:51 GMT-07:00

The Impact of Medication Cost on Dialysis Patients

Gedney, Nieltje — Tue, 20 Apr 2021 07:28:38 GMT-07:00

The Financial Burden of CKD: The Medication Edition

Gee, Patrick O. — Tue, 20 Apr 2021 07:28:38 GMT-07:00

Ulceration and Necrosis of Fingers and Toes in an ESKD Patient

Piggott, Raymond Simon — Thu, 24 Jun 2021 07:56:22 GMT-07:00

Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD

Wan, Eric Yuk Fai — Wed, 28 Apr 2021 06:05:35 GMT-07:00

Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age Neonates

Hingorani, Sangeeta — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Vaccines and Disease Relapses in Children with Nephrotic Syndrome

Angeletti, Andrea — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United States

McPherson, Laura J. — Wed, 26 May 2021 02:21:46 GMT-07:00

Post-Transplant CMV Glomerulitis

Aziz, Fahad — Wed, 10 Feb 2021 08:08:30 GMT-08:00

Inherited Kidney Complement Diseases

Lemaire, Mathieu — Wed, 03 Feb 2021 11:29:56 GMT-08:00

In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopathies (complement factor H, complement component 3, complement factor H–related proteins) or only aHUS (complement factor B, complement factor I, and membrane cofactor protein). Key questions and challenges are highlighted, along with potential avenues for future directions.

Depressive Symptoms and Rapid Kidney Function Decline

Wu, Mary H. — Sat, 29 May 2021 11:28:20 GMT-07:00

eGFR Testing around the World: Justice, Access, and Accuracy

Jha, Vivekanand — Thu, 07 Jan 2021 09:39:06 GMT-08:00

The Influence of Medical School Debt on Career Choices in Nephrology

Ginsberg, Charles — Mon, 07 Dec 2020 08:29:59 GMT-08:00

BLISS in the Treatment of Lupus Nephritis

Thurman, Joshua M. — Wed, 03 Feb 2021 11:29:56 GMT-08:00

Contextualizing the FHN Nocturnal Trial a Decade Later: How Nocturnal Home Hemodialysis Is Performed Matters to Outcomes

Pauly, Robert P. — Thu, 12 Nov 2020 10:50:00 GMT-08:00

Smoking Cessation and Coronary Artery Calcification in CKD

Lee, Mi Jung — Tue, 20 Apr 2021 11:01:50 GMT-07:00

Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure

Soomro, Qandeel H. — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function

Zhang, Zhuxian — Sat, 29 May 2021 11:11:56 GMT-07:00

Why Is the GFR So High?: Implications for the Treatment of Kidney Failure

Meyer, Timothy W. — Thu, 10 Dec 2020 07:26:23 GMT-08:00

The high GFR in vertebrates obligates large energy expenditure. Homer Smith’s teleologic argument that this high GFR was needed to excrete water as vertebrates evolved in dilute seas is outdated. The GFR is proportional to the metabolic rate among vertebrate species and higher in warm-blooded mammals and birds than in cold-blooded fish, amphibians, and reptiles. The kidney clearance of some solutes is raised above the GFR by tubular secretion, and we presume secretion evolved to eliminate particularly toxic compounds. In this regard, high GFRs may provide a fluid stream into which toxic solutes can be readily secreted. Alternatively, the high GFR may be required to clear solutes that are too large or too varied to be secreted, especially bioactive small proteins and peptides. These considerations have potentially important implications for the understanding and treatment of kidney failure.

Sincere Integration of Patients’ Perspectives into Kidney Care: Affirming and Adopting Patient Activation

Nair, Devika — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis

Chen, Kuan-Ting — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Reliability and Validity of the Patient Activation Measure in Kidney Disease: Results of Rasch Analysis

Lightfoot, Courtney J. — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Overweight and Obesity and Progression of ADPKD

Nowak, Kristen L. — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Dialyzing Acute Kidney Injury Patients after Hospital Discharge

McCoy, Ian — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Acute Kidney Injury Requiring Dialysis and Incident Dialysis Patient Outcomes in US Outpatient Dialysis Facilities

Dahlerus, Claudia — Thu, 27 May 2021 09:25:51 GMT-07:00

To Add Weight to Overweight

van Gastel, Maatje D.A. — Fri, 11 Jun 2021 12:06:56 GMT-07:00

Limited Significance of Antifactor H Antibodies in Patients with Membranous Nephropathy

Sethi, Amit — Thu, 15 Apr 2021 06:45:49 GMT-07:00

NephroTalk Multimodal Conservative Care Curriculum for Nephrology Fellows

Cohen, Robert A. — Fri, 12 Feb 2021 06:48:38 GMT-08:00

Conservative care, a comprehensive treatment path for advanced kidney disease most suitable for individuals unlikely to benefit from dialysis, is underutilized in the United States. One reason is an absence of robust education about this approach and how to discuss it with potential candidates. To address this need, we developed a multimodal conservative care curriculum for nephrology fellows. This curriculum consists of four online modules that address essential concepts and communication skills related to conservative care. It is followed by an in-person, interactive, “flipped classroom” session facilitated by designated nephrology educators at participating Accreditation Council for Graduate Medical Education nephrology training programs. Curriculum effect was assessed using surveys completed by participating fellows immediately before and following the curriculum and for participating nephrology educators following flipped classroom teaching; 148 nephrology trainees from 19 programs participated, with 108 completing both pre- and postcurriculum surveys. Mean self-reported preparedness (measured on a five-point Likert scale) increased significantly for all ten concepts taught in the curriculum. The mean correct score on eight knowledge questions increased from 69% to 82% following the curriculum (P<0.001). Fellows rated the curriculum highly and reported that they plan to practice skills learned. For the 19 nephrology program educators, the mean perceived preparedness to teach all curriculum domains increased after, compared with before, facilitating the flipped classroom, reaching significance for seven of the ten concepts measured. Data suggest that fellows' participation in a multimodal curriculum increased knowledge and preparation for fundamental conservative care concepts and communication skills. Fellows rated the curriculum highly. Educator participation appears to have increased preparedness for teaching the curriculum concepts, making it likely that future education in conservative care will become more widespread. Herein, we describe the curriculum content, which we have made publicly available in order to encourage broader implementation, and its effect on participating fellows and the nephrology educators who facilitated it.

Dialysis and Transplant Access: Kidney Capitalism at a Crossroads?

Raghavan, Divya — Wed, 26 May 2021 02:53:21 GMT-07:00

Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force

Delgado, Cynthia — Fri, 09 Apr 2021 01:00:12 GMT-07:00

For almost two decades, equations that use serum creatinine, age, sex, and race to eGFR have included “race” as Black or non-Black. Given considerable evidence of disparities in health and healthcare delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase one, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made.

Advance Care Planning in Older Adults with CKD: Patient, Care Partner, and Clinician Perspectives

Ladin, Keren — Wed, 07 Apr 2021 10:27:29 GMT-07:00

Race and the Estimation of GFR: Getting it Right

Feldman, Harold I. — Fri, 09 Apr 2021 01:00:12 GMT-07:00

Medicaid Expansion and Incidence of Kidney Failure among Nonelderly Adults

Thorsness, Rebecca — Thu, 01 Apr 2021 09:56:38 GMT-07:00

Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness

Schlingmann, Karl P. — Fri, 02 Apr 2021 09:16:23 GMT-07:00

Initial Effects of COVID-19 on Patients with ESKD

Weinhandl, Eric D. — Thu, 08 Apr 2021 07:35:09 GMT-07:00

Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus

Petrillo, Federica — Tue, 16 Mar 2021 07:22:13 GMT-07:00

Could NAD+ Precursor Supplements Induce a Legacy of Protection against Diabetic Nephropathy?

Hyndman, Kelly A. — Wed, 14 Apr 2021 08:35:30 GMT-07:00

Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy

Yasuda, Itaru — Thu, 01 Apr 2021 09:56:37 GMT-07:00

How to Get Started with Single Cell RNA Sequencing Data Analysis

Balzer, Michael S. — Mon, 15 Mar 2021 11:23:41 GMT-07:00

Over the last 5 years, single cell methods have enabled the monitoring of gene and protein expression, genetic, and epigenetic changes in thousands of individual cells in a single experiment. With the improved measurement and the decreasing cost of the reactions and sequencing, the size of these datasets is increasing rapidly. The critical bottleneck remains the analysis of the wealth of information generated by single cell experiments. In this review, we give a simplified overview of the analysis pipelines, as they are typically used in the field today. We aim to enable researchers starting out in single cell analysis to gain an overview of challenges and the most commonly used analytical tools. In addition, we hope to empower others to gain an understanding of how typical readouts from single cell datasets are presented in the published literature.

An Introduction to Qualitative Inquiry

Butler, Catherine R. — Wed, 26 May 2021 02:56:33 GMT-07:00

Black Race Coefficient in GFR Estimation and Diabetes Medications in CKD: National Estimates

Walther, Carl P. — Thu, 08 Apr 2021 08:00:09 GMT-07:00

Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes

Yang, Jingping — Fri, 26 Mar 2021 06:14:51 GMT-07:00

Advance Care Planning in Kidney Disease: A Tale of Two Conversations

Schell, Jane O. — Wed, 26 May 2021 02:56:33 GMT-07:00

Low Health Literacy is Associated with the Onset of CKD during the Life Course

Gurgel do Amaral, Matheus S. — Thu, 25 Mar 2021 09:05:32 GMT-07:00

On the Increased Event Rate of Urinary Tract Infection and Pneumonia in CKD Patients Treated with Roxadustat for Anemia

Eleftheriadis, Theodoros — Tue, 13 Apr 2021 08:18:31 GMT-07:00

Tubuloglomerular Feedback Synchronization in Nephrovascular Networks

Zehra, Tayyaba — Thu, 08 Apr 2021 08:00:10 GMT-07:00

To perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by the generic myogenic response and the kidney-specific tubuloglomerular feedback (TGF) mechanism. The central theme of this paper is that, to achieve autoregulation, nephrons do not work as single units to manage their individual blood flows, but rather communicate electrically over long distances to other nephrons via the vascular tree. Accordingly, we define the nephrovascular unit (NVU) to be a structure consisting of the nephron, glomerulus, afferent arteriole, and efferent arteriole. We discuss features that require and enable distributed autoregulation mediated by TGF across the kidney. These features include the highly variable topology of the renal vasculature which creates variability in circulation and the potential for mismatch between tubular oxygen demand and delivery; the self-sustained oscillations in each NVU arising from the autoregulatory mechanisms; and the presence of extensive gap junctions formed by connexins and their properties that enable long-distance transmission of TGF signals. The existence of TGF synchronization across the renal microvascular network enables an understanding of how NVUs optimize oxygenation-perfusion matching while preventing transmission of high systemic pressure to the glomeruli, which could lead to progressive glomerular and vascular injury.

Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study

Park, Sehoon — Tue, 30 Mar 2021 07:30:31 GMT-07:00

Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial

De Vriese, An S. — Mon, 22 Mar 2021 08:16:39 GMT-07:00

Addendum: Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and Reflect

American Society of Nephrology — Fri, 28 May 2021 11:00:33 GMT-07:00

How Many Disparate Measurements of Kidney Function Unfairly Allow Selected Candidates to Accumulate Time on the Deceased Donor Kidney Transplant Waiting List?

Steiner, Robert W. — Fri, 21 May 2021 01:58:52 GMT-07:00

The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate Podocytes

Mysh, Michael — Thu, 01 Apr 2021 09:56:37 GMT-07:00

Authors’ Reply

Fishbane, Steven — Tue, 13 Apr 2021 08:05:47 GMT-07:00

Exploring the Complexity of Death-Censored Kidney Allograft Failure

Mayrdorfer, Manuel — Wed, 21 Apr 2021 06:27:50 GMT-07:00

ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte Damage

Sachs, Marlies — Tue, 30 Mar 2021 07:30:32 GMT-07:00

A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)

Pergola, Pablo E. — Thu, 25 Mar 2021 09:05:33 GMT-07:00

Hypercholesterolemia in Progressive Renal Failure Is Associated with Changes in Hepatic Heparan Sulfate - PCSK9 Interaction

Shrestha, Pragyi — Tue, 23 Mar 2021 07:44:29 GMT-07:00

National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race

Duggal, Vishal — Thu, 06 May 2021 05:18:48 GMT-07:00

Renal Recovery and Mortality Risk among Patients with Hepatorenal Syndrome Receiving Chronic Maintenance Dialysis

McAllister, Sophie — Wed, 03 Mar 2021 07:43:39 GMT-08:00

Utility of Kinetic GFR for Predicting Severe Persistent AKI in Critically Ill Children and Young Adults

Menon, Shina — Wed, 17 Mar 2021 01:22:31 GMT-07:00

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? CON

Glassock, Richard J. — Thu, 14 Jan 2021 06:25:51 GMT-08:00

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? PRO

Derebail, Vimal K. — Thu, 14 Jan 2021 06:25:51 GMT-08:00

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? COMMENTARY

Falk, Ronald J. — Thu, 14 Jan 2021 06:25:51 GMT-08:00

Introduction to Supervised Machine Learning

Biswas, Aditya — Wed, 03 Mar 2021 09:28:26 GMT-08:00

The Potential Role of the Gut Microbiota in Kidney Transplantation

Huang, Jennifer — Fri, 05 Mar 2021 07:38:15 GMT-08:00

Kidney–Gut Crosstalk in AKI

Jo, Sang Kyung — Mon, 22 Feb 2021 11:24:26 GMT-08:00

A Hyaluronan Synthesis Inhibitor Delays the Progression of Diabetic Kidney Disease in A Mouse Experimental Model

Selman, Guillermo — Tue, 02 Mar 2021 10:28:08 GMT-08:00

Free Deoxycholic Acid Exacerbates Vascular Calcification in CKD through ER Stress-Mediated ATF4 Activation

Miyazaki-Anzai, Shinobu — Fri, 26 Mar 2021 07:32:10 GMT-07:00

Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction

Ren, Jiafa — Thu, 18 Mar 2021 06:22:47 GMT-07:00

Whole-Exome Sequencing Application for Genetic Diagnosis of Kidney Diseases: A Study from Southwest of Iran

Zamani, Mina — Wed, 10 Mar 2021 01:23:10 GMT-08:00

The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis

Saleem, Mohammad — Fri, 26 Mar 2021 01:24:02 GMT-07:00

Are the Protective Effects of SGLT2 Inhibitors a “Class-Effect” or Are There Differences between Agents?

Schmidt, Darren W. — Fri, 05 Feb 2021 09:45:50 GMT-08:00

Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy

Marumoto, Hirokazu — Wed, 10 Mar 2021 11:30:25 GMT-08:00

Worsening Kidney Function, Proteinuria, and Hematuria in a Patient with CLL

Chopra, Pavan — Thu, 27 May 2021 01:00:23 GMT-07:00

Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants

Hallows, Kenneth R. — Thu, 11 Mar 2021 09:36:45 GMT-08:00

Renal Hemodynamics, Function, and Oxygenation in Critically Ill Patients and after Major Surgery

Ricksten, Sven-Erik — Wed, 03 Mar 2021 09:28:26 GMT-08:00

This review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal dysfunction, such as those with postoperative AKI, those in early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass, or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function, and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that, for all of these groups of patients, the common denominator is that renal oxygenation is impaired due to a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.

Role of Virus-Specific T Cell Therapy for Cytomegalovirus and BK Infections in Kidney Transplant Recipients

Parajuli, Sandesh — Fri, 26 Mar 2021 12:18:40 GMT-07:00

Cytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well described. However, despite improvement in screening and prophylaxis strategies, CMV and BKV continue to negatively affect both short- and long-term graft survival. Adequate cell-mediated immunity is essential for the control and prevention of opportunistic viral infections, such as CMV and BKV. Therefore, immune reconstitution, in particular T cell recovery, is a key factor in antiviral control after kidney transplantation. Cell-based immunotherapy offers an attractive alternative approach to traditional interventions. Adoptive T cell transfer, via infusions of allogeneic virus-specific T lymphocytes is capable of restoring virus-specific T cell immunity, and are safe and effective in the treatment of viral infections after hematopoietic stem cell transplantation. In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation. On the basis of the available data, virus-specific T cell therapy may be a promising addition to the antiviral treatment armamentarium after kidney transplantation. Future studies are needed to more clearly define the efficacy and risks of virus-specific T cell therapy in the kidney transplant population.

AKI in a Patient with Fever, Rash, and Joint Pain

Aron, Abraham W. — Thu, 27 May 2021 01:00:23 GMT-07:00

Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKD

Brar, Ranveer S. — Fri, 26 Mar 2021 06:05:27 GMT-07:00

Identification of Patients with CKD in Medical Databases

Vestergaard, Søren Viborg — Thu, 11 Mar 2021 08:20:27 GMT-08:00

Racial Differences in AKI Incidence Following Percutaneous Coronary Intervention

Lunyera, Joseph — Fri, 18 Dec 2020 11:57:36 GMT-08:00

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time

Ku, Elaine — Tue, 23 Feb 2021 11:36:42 GMT-08:00

Promoting Equity in Eligibility for Registration on the Kidney Transplantation Waiting List: Looking beyond eGFRcr

Levey, Andrew S. — Tue, 23 Feb 2021 11:21:27 GMT-08:00

Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank

Zhao, Jie V. — Mon, 14 Dec 2020 09:25:12 GMT-08:00

Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome

Mann, Nina — Tue, 16 Feb 2021 08:29:16 GMT-08:00

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)

Rivero, Jesús — Mon, 29 Mar 2021 10:58:19 GMT-07:00

Trust the Patient: An Unusual Case of Metabolic Alkalosis

Hoenig, Melanie Paige — Tue, 16 Mar 2021 07:19:36 GMT-07:00

Mass Disasters and Burnout in Nephrology Personnel

Sever, Mehmet Sukru — Thu, 07 Jan 2021 09:39:06 GMT-08:00

Mass disasters result in extensive health problems and make health care delivery problematic, as has been the case during the COVID-19 pandemic. Although COVID-19 was initially considered a pulmonary problem, it soon became clear that various other organs were involved. Thus, many care providers, including kidney health personnel, were overwhelmed or developed burnout. This review aims to describe the spectrum of burnout in mass disasters and suggests solutions specifically for nephrology personnel by extending previous experience to the COVID-19 pandemic. Burnout (a psychologic response to work-related stress) is already a frequent part of routine nephrology practice and, not surprisingly, is even more common during mass disasters due to increased workload and specific conditions, in addition to individual factors. Avoiding burnout is essential to prevent psychologic and somatic health problems in personnel as well as malpractice, understaffing, and inadequate health care delivery, all of which increase the health care burden of disasters. Burnout may be prevented by predisaster organizational measures, which include developing an overarching plan and optimizing health care infrastructure, and ad hoc disaster-specific measures that encompass both organizational and individual measures. Organizational measures include increasing safety, decreasing workload and fear of malpractice, optimizing medical staffing and material supplies, motivating personnel, providing mental health support, and enabling flexibility in working circumstances. Individual measures include training on coping with stress and problematic conditions, minimizing the stigma of emotional distress, and maintaining physical health. If these measures fall short, asking for external help is mandatory to avoid an inefficient disaster health care response. Minimizing burnout by applying these measures will improve health care provision, thus saving as many lives as possible.

Outcomes of COVID-19 in CKD Patients

Pakhchanian, Haig — Mon, 08 Feb 2021 09:47:53 GMT-08:00

Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic Studies

Lanktree, Matthew B. — Mon, 20 Jul 2020 02:00:20 GMT-07:00

Autosomal dominant polycystic kidney disease is the most common monogenic cause of ESKD. Genetic studies from patients and animal models have informed disease pathobiology and strongly support a “threshold model” in which cyst formation is triggered by reduced functional polycystin dosage below a critical threshold within individual tubular epithelial cells due to (1) germline and somatic PKD1 and/or PKD2 mutations, (2) mutations of genes (e.g., SEC63, SEC61B, GANAB, PRKCSH, DNAJB11, ALG8, and ALG9) in the endoplasmic reticulum protein biosynthetic pathway, or (3) somatic mosaicism. Genetic testing has the potential to provide diagnostic and prognostic information in cystic kidney disease. However, mutation screening of PKD1 is challenging due to its large size and complexity, making it both costly and labor intensive. Moreover, conventional Sanger sequencing–based genetic testing is currently limited in elucidating the causes of atypical polycystic kidney disease, such as within-family disease discordance, atypical kidney imaging patterns, and discordant disease severity between total kidney volume and rate of eGFR decline. In addition, environmental factors, genetic modifiers, and somatic mosaicism also contribute to disease variability, further limiting prognostication by mutation class in individual patients. Recent innovations in next-generation sequencing are poised to transform and extend molecular diagnostics at reasonable costs. By comprehensive screening of multiple cystic disease and modifier genes, targeted gene panel, whole-exome, or whole-genome sequencing is expected to improve both diagnostic and prognostic accuracy to advance personalized medicine in autosomal dominant polycystic kidney disease.

A Dialysis Patient’s View on Dialysis Employment Loss

Ditschman, Erich — Thu, 15 Apr 2021 07:54:43 GMT-07:00

A Patient Perspective on Genetic Testing for ADPKD

Odland, Dwight — Thu, 30 Jul 2020 07:14:46 GMT-07:00

Social Determinants of Kidney Health

Norris, Keith C. — Wed, 13 Jan 2021 07:09:12 GMT-08:00

The Seen and the Unseen: Race and Social Inequities Affecting Kidney Care

Boulware, L. Ebony — Wed, 13 Jan 2021 07:09:12 GMT-08:00

Social Determinants of Health in People with Kidney Disease

Weinstein, Alan M. — Wed, 13 Jan 2021 07:09:13 GMT-08:00

Reducing the Burden of CKD among Latinx

Pereira, Rocio I. — Wed, 13 Jan 2021 07:09:13 GMT-08:00

Personal Experiences of Patients in the Interaction of Culture and Kidney Disease

Cukor, Daniel — Wed, 13 Jan 2021 07:09:13 GMT-08:00

The Pathogenesis of Race and Ethnic Disparities

Powe, Neil R. — Wed, 13 Jan 2021 07:09:12 GMT-08:00

Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome

Kalantar-Zadeh, Kamyar — Tue, 27 Apr 2021 09:07:41 GMT-07:00

Uromodulin, Salt, and 24-Hour Blood Pressure in the General Population

Ponte, Belen — Thu, 21 Jan 2021 08:10:09 GMT-08:00

Twenty-First Century Solutions to Increase Medication Optimization and Safety in Kidney Transplant Patients

St. Peter, Wendy L. — Fri, 30 Apr 2021 11:43:51 GMT-07:00

Prasugrel and Ticagrelor in Patients with Drug-Eluting Stents and Kidney Failure

Mavrakanas, Thomas A. — Fri, 02 Apr 2021 09:27:23 GMT-07:00

Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis

Bushinsky, David A. — Wed, 07 Apr 2021 09:00:59 GMT-07:00

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients

Hall, Isaac E. — Wed, 10 Mar 2021 08:09:01 GMT-08:00

Novel Therapeutic Options for Cardiovascular Disease with CKD

Zoccali, Carmine — Tue, 27 Apr 2021 09:17:42 GMT-07:00

Pharmacist-Led Mobile Health Intervention and Transplant Medication Safety

Gonzales, Haley M. — Fri, 30 Apr 2021 11:25:54 GMT-07:00

Moving beyond Sedentarism in CKD

Kim, Tae Youn — Thu, 22 Apr 2021 11:09:17 GMT-07:00

Targeting Sedentary Behavior in CKD

Lyden, Kate — Thu, 22 Apr 2021 10:51:28 GMT-07:00

Growing Understanding of the Antigenic Basis for Membranous Nephropathy

Brglez, Vesna — Tue, 13 Apr 2021 09:02:45 GMT-07:00

Cognitive Dysfunction and Gait Abnormalities in CKD

Koren, Melanie J. — Tue, 06 Apr 2021 07:54:42 GMT-07:00

Estimated Loss of Lifetime Employment Duration for Patients Undergoing Maintenance Dialysis in Taiwan

Chang, Yu-Tzu — Thu, 15 Apr 2021 07:41:26 GMT-07:00

Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement Therapy

Hryciw, Nicole — Wed, 28 Oct 2020 06:51:19 GMT-07:00

Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.

Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese Patients

Wang, Guoqin — Tue, 13 Apr 2021 08:27:15 GMT-07:00

Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated Vasculitis

Gan, Poh-Yi — Wed, 31 Mar 2021 11:43:04 GMT-07:00

Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States

Whelan, Adrian M. — Fri, 12 Mar 2021 11:18:20 GMT-08:00

Kidney Transplant Rejection Clusters and Graft Outcomes: Revisiting Banff in the Era of “Big Data”

Vasquez-Rios, George — Tue, 06 Apr 2021 07:32:39 GMT-07:00

Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering

Vaulet, Thibaut — Tue, 09 Mar 2021 07:02:39 GMT-08:00

COVID-19 and Dialysis Patients: Unsolved Problems in Early 2021

Kliger, Alan S. — Fri, 26 Feb 2021 10:17:36 GMT-08:00

SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?

Heldman, Madeleine R. — Wed, 24 Mar 2021 07:54:56 GMT-07:00

COVID-19 and AKI: Where Do We Stand?

Palevsky, Paul M. — Fri, 26 Feb 2021 10:17:36 GMT-08:00

Impact of the COVID-19 Pandemic on Nephrology Fellow Training and Well-Being in the United States: A National Survey

Pivert, Kurtis A. — Wed, 03 Mar 2021 08:44:12 GMT-08:00

Kinetics of Anti–SARS-CoV-2 IgG Antibodies in Hemodialysis Patients Six Months after Infection

Sakhi, Hamza — Fri, 26 Feb 2021 10:17:37 GMT-08:00

IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic Syndrome

Cugno, Massimo — Fri, 12 Mar 2021 11:18:20 GMT-08:00

Deletion of Myeloid Interferon Regulatory Factor 4 (Irf4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and Activation

Sasaki, Kensuke — Mon, 22 Feb 2021 07:24:26 GMT-08:00

Receptor-Mediated Endocytosis and Differentiation in Proximal Tubule Cell Systems

Berquez, Marine — Mon, 12 Apr 2021 08:29:14 GMT-07:00

Urinary Vesicles: Are They Ready for Real-World Use?

Hunter, Robert W. — Mon, 29 Mar 2021 10:41:45 GMT-07:00

Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits

Zand, Ladan — Mon, 08 Mar 2021 12:11:24 GMT-08:00

BP in Young Adults with CKD and Associations with Cardiovascular Events and Decline in Kidney Function

Kula, Alexander J. — Wed, 10 Mar 2021 05:57:48 GMT-08:00

Authors’ Reply

Reese, Peter. P. — Wed, 28 Apr 2021 06:20:44 GMT-07:00

Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD

Ramspek, Chava L. — Mon, 08 Mar 2021 12:11:24 GMT-08:00

Obituary for Robert Schrier

Berl, Tomas — Mon, 29 Mar 2021 09:51:41 GMT-07:00

The Urine Anion Gap: Common Misconceptions

Uribarri, Jaime — Fri, 05 Mar 2021 05:55:20 GMT-08:00

Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH4) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH4. This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e., UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH4 excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH4, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.

Procurement Biopsy Data Quality Limits Comparability of United States and French Deceased Donor Kidney Biopsies

Husain, S. Ali — Wed, 28 Apr 2021 06:37:50 GMT-07:00

Renal Inflammation Induces Salt Sensitivity in Male db/db Mice through Dysregulation of ENaC

Veiras, Luciana C. — Wed, 17 Mar 2021 08:36:21 GMT-07:00

Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension

Haruhara, Kotaro — Wed, 24 Feb 2021 06:58:01 GMT-08:00

Crumbs2 Is an Essential Slit Diaphragm Protein of the Renal Filtration Barrier

Möller-Kerutt, Annika — Tue, 09 Mar 2021 07:02:39 GMT-08:00

The Rhesus Macaque Serves As a Model for Human Lateral Branch Nephrogenesis

Schuh, Meredith P. — Wed, 31 Mar 2021 11:43:03 GMT-07:00

Comparing Approaches to Normalize, Quantify, and Characterize Urinary Extracellular Vesicles

Blijdorp, Charles J. — Mon, 29 Mar 2021 10:58:37 GMT-07:00

Monkeying about with Nephron Formation

Smyth, Ian M. — Wed, 07 Apr 2021 11:05:56 GMT-07:00

Protocadherin 7–Associated Membranous Nephropathy

Sethi, Sanjeev — Thu, 08 Apr 2021 08:07:41 GMT-07:00

This Month's Highlights

American Society of Nephrology — Sat, 01 May 2021 06:48:23 GMT-07:00

Protective Role of the M-Sec–Tunneling Nanotube System in Podocytes

Barutta, Federica — Mon, 15 Mar 2021 11:23:42 GMT-07:00

Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including Glucose-Lowering Drugs and Diuretics

Lam, David — Mon, 01 Feb 2021 12:07:36 GMT-08:00

Lower Urinary Tract Symptoms Should Be Queried When Initiating Sodium Glucose Co-Transporter 2 Inhibitors

Krepostman, Nicolas — Wed, 03 Feb 2021 09:27:12 GMT-08:00

Dialysis Care around the World: A Global Perspectives Series

Lee, Timmy — Fri, 26 Feb 2021 12:04:31 GMT-08:00

Opportunities To Improve Diabetes Care in the Hemodialysis Unit: A Cohort Study in Ontario, Canada

Clemens, Kristin K. — Fri, 19 Feb 2021 10:37:14 GMT-08:00

Podocyte Lipotoxicity in CKD

Kim, Jin-Ju — Fri, 26 Feb 2021 09:59:35 GMT-08:00

CKD represents the ninth most common cause of death in the United States but, despite this large health burden, treatment options for affected patients remain limited. To remedy this, several relevant pathways have been identified that may lead to novel therapeutic options. Among them, altered renal lipid metabolism, first described in 1982, has been recognized as a common pathway in clinical and experimental CKD of both metabolic and nonmetabolic origin. This observation has led many researchers to investigate the cause of this renal parenchyma lipid accumulation and its downstream effect on renal structure and function. Among key cellular components of the kidney parenchyma, podocytes are terminally differentiated cells that cannot be easily replaced when lost. Clinical and experimental evidence supports a role of reduced podocyte number in the progression of CKD. Given the importance of the podocytes in the maintenance of the glomerular filtration barrier and the accumulation of TG and cholesterol-rich lipid droplets in the podocyte and glomerulus in kidney diseases that cause CKD, understanding the upstream cause and downstream consequences of lipid accumulation in podocytes may lead to novel therapeutic opportunities. In this review, we hope to consolidate our understanding of the causes and consequences of dysregulated renal lipid metabolism in CKD development and progression, with a major focus on podocytes.

Qualitative Research in Nephrology: An Introduction to Methods and Critical Appraisal

Amir, Noa — Mon, 22 Feb 2021 09:50:11 GMT-08:00

COVID-19–associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the Nephron

Bouquegneau, Antoine — Fri, 12 Feb 2021 09:23:36 GMT-08:00

Equity Is Key to Build Back Better after COVID-19: Prioritize Noncommunicable Diseases and Kidney Health

Luyckx, Valerie Ann — Mon, 01 Feb 2021 12:07:36 GMT-08:00

AKI in COVID-19–Associated Multisystem Inflammatory Syndrome in Children (MIS-C)

Lipton, Marissa — Wed, 03 Feb 2021 09:27:12 GMT-08:00

AKI in Hospitalized Patients with COVID-19 and Seasonal Influenza: A Comparative Analysis

Bhasin, Bhavna — Fri, 26 Feb 2021 12:04:31 GMT-08:00

Electrolyte Changes in Contemporary Hemodialysis: A Secondary Analysis of the Monitoring in Dialysis Study

Correa, Simon — Fri, 19 Feb 2021 06:11:19 GMT-08:00

Citric Acid–Containing Dialysate and Survival Rate in the Dialysis Outcomes and Practice Patterns Study

Ureña-Torres, Pablo — Thu, 04 Feb 2021 01:57:27 GMT-08:00

Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) Vasculitis

Jain, Koyal — Fri, 05 Feb 2021 09:45:50 GMT-08:00

ANCA vasculitis is a small-vessel vasculitis (SVV) resulting in inflammation of small- and medium-sized blood vessels. Since the initial description of SVV, there have been tremendous advances in our understanding of its pathogenesis. Over the last decade, we have made significant progress in understanding the pathogenesis and improving the treatment and prognosis of patients with ANCA vasculitis. Patient and renal survival has improved, and treatment is moving toward individualizing care, minimizing severe adverse events, and preventing relapse. This review focuses on treatment updates in ANCA vasculitis, duration of therapy, and management of relapses. We also describe the existing treatment protocols used at our institution.

Acute Dyspnea in a Young Woman Following Percutaneous Nephrostomy Tube Placement

Khin, Ei — Thu, 29 Apr 2021 08:25:24 GMT-07:00

Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts

Wolf-Doty, Theresa K. — Wed, 03 Feb 2021 11:36:20 GMT-08:00

Implementation of an Electronic Catheter Checklist in Outpatient Hemodialysis Facilities: Results of a Pilot Quality Improvement Project

Mokrzycki, Michele H. — Tue, 09 Feb 2021 11:16:43 GMT-08:00

Functional Status in CKD: What Measures to Use?

Schrauben, Sarah J. — Thu, 29 Apr 2021 08:25:24 GMT-07:00

Clinical Spectrum and Renal Outcome of Cryoglobulinemia in Hong Kong

Fung, Winston Wing-Shing — Mon, 22 Feb 2021 07:26:47 GMT-08:00

Associations of Performance-Based Functional Assessments and Adverse Outcomes in CKD

Belkin, Mitchell D. — Tue, 19 Jan 2021 12:41:10 GMT-08:00

Targeting Patient and Health System Barriers To Improve Rates of Hemodialysis Initiation with an Arteriovenous Access

Flythe, Jennifer E. — Fri, 26 Feb 2021 12:04:31 GMT-08:00

AKI, Anemia, and Thrombocytopenia in a Patient with Leg and Flank Pain

Lara Prado, Jesús Iván — Thu, 29 Apr 2021 08:25:24 GMT-07:00

Center-Effect of Incident Hemodialysis Vascular Access Use: Analysis of a Bi-national Registry

Ng, Samantha — Tue, 09 Feb 2021 11:16:43 GMT-08:00

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux

Verbitsky, Miguel — Wed, 17 Feb 2021 08:19:08 GMT-08:00

mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 Mutants

Zhu, Ping — Thu, 11 Feb 2021 11:40:06 GMT-08:00

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study

Green, Daniel M. — Tue, 02 Mar 2021 06:36:17 GMT-08:00

Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in Japan

Udagawa, Tomohiro — Tue, 19 Jan 2021 09:27:56 GMT-08:00

Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis

Shirai, Yoko — Tue, 01 Dec 2020 10:20:45 GMT-08:00

Childhood Cancer and the Risk of ESKD

Calderon-Margalit, Ronit — Thu, 12 Nov 2020 10:51:18 GMT-08:00

Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial

Ahlenstiel-Grunow, Thurid — Tue, 15 Dec 2020 09:50:57 GMT-08:00

Measuring Patient Experience with Home Dialysis in the United States

Brady, Brian M. — Tue, 30 Mar 2021 07:25:40 GMT-07:00

Inherited Tubulopathies of the Kidney

Downie, Mallory L. — Wed, 01 Apr 2020 07:10:22 GMT-07:00

The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.

Patient Experiences with Home Dialysis

Myers, James — Tue, 30 Mar 2021 07:25:40 GMT-07:00

Integrating Patient Perspectives into Medical Device Regulatory Decision Making to Advance Innovation in Kidney Disease

Tarver, Michelle E. — Wed, 03 Mar 2021 06:28:25 GMT-08:00

Incorporating Patient Preferences via Bayesian Decision Analysis

Chaudhuri, Shomesh E. — Wed, 03 Mar 2021 06:28:26 GMT-08:00

Using Patient Preference Information to Inform Regulatory Decision Making

Flythe, Jennifer E. — Wed, 03 Mar 2021 06:28:25 GMT-08:00

Legitimization and Incorporation of Patient Preferences

Conway, Paul T. — Wed, 03 Mar 2021 06:28:26 GMT-08:00

Overview of Various Components of the Science of Patient Input

Sheldon, Murray — Wed, 03 Mar 2021 06:28:25 GMT-08:00

Expression of CD147 and Cyclophilin A in Kidneys of Patients with COVID-19

Su, Hua — Wed, 02 Dec 2020 01:21:23 GMT-08:00

Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients

Karras, Alexandre — Tue, 23 Feb 2021 06:21:35 GMT-08:00

A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis Facility

Labriola, Laura — Wed, 18 Nov 2020 05:17:05 GMT-08:00

SGLT2 Inhibitors in Diabetic Kidney Disease

Zoungas, Sophia — Wed, 03 Feb 2021 11:29:56 GMT-08:00

Effect of Aerobic Exercise on Dialysis-Related Symptoms in Individuals Undergoing Maintenance Hemodialysis

Hargrove, Nicholas — Thu, 25 Mar 2021 09:10:35 GMT-07:00

Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients

Ong, Stephanie W. — Thu, 18 Mar 2021 08:22:28 GMT-07:00

Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine Project

Tuttle, Katherine R. — Mon, 30 Nov 2020 05:37:33 GMT-08:00

The Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP. Patients with CKD and AKI and clinicians from the study sites are members of the Community Engagement Committee, with representation on other KPMP committees. They participate in KPMP deliberations to address scientific, clinical, logistic, analytic, ethical, and community engagement issues. The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians. Patients led development of essential study components, including the informed consent process, no-fault harm insurance coverage, the ethics statement, return of results plan, a “Patient Primer” for scientists and the public, and Community Advisory Boards. As members across other KPMP committees, the Community Engagement Committee assures that the science is developed and conducted in a manner relevant to study participants and the clinical community. Patients have guided the KPMP to produce research aligned with their priorities. The Community Engagement Committee partnership has set new benchmarks for patient leadership in precision medicine research.

Risk Factors for CKD Progression

Hannan, Mary — Wed, 11 Nov 2020 10:21:53 GMT-08:00

The Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories: (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.

Digital Solutions to Improve Medication Safety in CKD

Wagner, Lee-Ann — Thu, 18 Mar 2021 08:38:17 GMT-07:00

Nephronophthisis in Young Adults Phenocopying Thrombotic Microangiopathy and Severe Nephrosclerosis

Doreille, Alice — Wed, 02 Dec 2020 10:45:39 GMT-08:00

Therapeutic Options to Improve Cardiovascular Outcomes with Long-Term Hemodialysis

Clark-Cutaia, Maya N. — Mon, 29 Mar 2021 01:16:32 GMT-07:00

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism

Shoji, Tetsuo — Mon, 08 Mar 2021 08:01:13 GMT-08:00

Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis

Ruggenenti, Piero — Mon, 29 Mar 2021 01:08:09 GMT-07:00

The Promise and Challenge of Aerobic Exercise in People Undergoing Long-Term Hemodialysis

Johansen, Kirsten L. — Thu, 25 Mar 2021 09:25:11 GMT-07:00

A New View of Iron Management in Heart Failure

Uppal, Nupur N. — Mon, 29 Mar 2021 11:41:21 GMT-07:00

Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKD

Cho, Monique E. — Mon, 29 Mar 2021 11:20:57 GMT-07:00

Development and Content Validity of a Patient-Reported Experience Measure for Home Dialysis

Rivara, Matthew B. — Tue, 30 Mar 2021 07:25:41 GMT-07:00

Comparative Analysis of SARS-CoV-2 Reproduction Rates in the Dialysis and General Populations

Cherif, Alhaji — Mon, 08 Mar 2021 12:11:25 GMT-08:00

Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019

Teoh, Jeremy Yuen-Chun — Fri, 22 Jan 2021 07:39:08 GMT-08:00

A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids

Wysocki, Jan — Mon, 01 Feb 2021 07:16:13 GMT-08:00

This Month's Highlights

American Society of Nephrology — Wed, 31 Mar 2021 11:00:43 GMT-07:00

Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis

Ginley, Brandon — Tue, 23 Feb 2021 10:57:49 GMT-08:00

Automated Quantification of Chronic Changes in the Kidney Biopsy: Another Step in the Right Direction

Hodgin, Jeffrey B. — Mon, 08 Mar 2021 01:34:02 GMT-08:00

Failure to Advance Access to Kidney Transplantation over Two Decades in the United States

Schold, Jesse D. — Thu, 11 Feb 2021 11:40:05 GMT-08:00

Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and Reflect

Gill, John S. — Tue, 02 Mar 2021 06:36:18 GMT-08:00

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

El Fekih, Rania — Wed, 03 Mar 2021 08:44:12 GMT-08:00

The Preventable Productivity Burden of Kidney Disease in Australia

Savira, Feby — Tue, 09 Mar 2021 08:53:11 GMT-08:00

Cardiovascular Risk Based on ASCVD and KDIGO Categories in Chinese Adults: A Nationwide, Population-Based, Prospective Cohort Study

Xu, Yu — Thu, 04 Mar 2021 08:51:40 GMT-08:00

Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to Dialysis

Sumida, Keiichi — Fri, 05 Feb 2021 10:53:21 GMT-08:00

NBCn1 Increases NH4+ Reabsorption Across Thick Ascending Limbs, the Capacity for Urinary NH4+ Excretion, and Early Recovery from Metabolic Acidosis

Olsen, Jeppe S. M. — Thu, 07 Jan 2021 09:45:44 GMT-08:00

QALYs, DALYs and Now PALYs: Strengthening the Argument for Prevention of CKD

Canney, Mark — Tue, 09 Mar 2021 08:40:31 GMT-08:00

Authors’ Reply

Akizawa, Tadao — Mon, 01 Mar 2021 08:44:24 GMT-08:00

Me Or Your Own Eyes: RNA-Seq and the Kidney

Ellison, David H. — Thu, 04 Mar 2021 09:17:20 GMT-08:00

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

Scolari, Francesco — Mon, 01 Mar 2021 08:11:46 GMT-08:00

Management of Obesity in Adults with CKD

Friedman, Allon N. — Thu, 18 Feb 2021 06:49:58 GMT-08:00

Obesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.

1α,25-Dihydroxyvitamin D3 Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas

Singh, Avishek K. — Wed, 24 Feb 2021 06:58:00 GMT-08:00

Roxadustat for Renal Anemia in ESRD from PKD Patients: Is It Safe Enough?

Liu, Fei — Mon, 01 Mar 2021 08:58:32 GMT-08:00

A Comprehensive Map of mRNAs and Their Isoforms across All 14 Renal Tubule Segments of Mouse

Chen, Lihe — Thu, 04 Mar 2021 09:32:56 GMT-08:00

Targeted Single-Cell RNA-seq Identifies Minority Cell Types of Kidney Distal Nephron

Chen, Lihe — Thu, 04 Mar 2021 09:32:57 GMT-08:00

A Call to Action for Addressing Disparities and Increasing Diversity in Academic Nephrology

Lyas, Claretha — Wed, 27 Jan 2021 01:35:26 GMT-08:00

A Comparison Study of Coronavirus Disease 2019 Outcomes in Hospitalized Kidney Transplant Recipients

Mansour, Sherry G. — Tue, 12 Jan 2021 08:06:07 GMT-08:00

Machine Learning for Prediction of Patients on Hemodialysis with an Undetected SARS-CoV-2 Infection

Monaghan, Caitlin K. — Wed, 13 Jan 2021 01:56:25 GMT-08:00

Progress toward the Clinical Application of Mesenchymal Stromal Cells and Other Disease-Modulating Regenerative Therapies: Examples from the Field of Nephrology

Hickson, LaTonya J. — Wed, 27 Jan 2021 01:35:26 GMT-08:00

Drawing from basic knowledge of stem-cell biology, embryonic development, wound healing, and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical-translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient’s cells, without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease-modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associated AKI (SA-AKI), diabetic kidney disease (DKD), and kidney transplantation (KTx). As we describe, the DMRT that has most consistently progressed to human clinical trials for these indications is mesenchymal stem/stromal cells (MSCs), which potently modulate ischemic, inflammatory, profibrotic, and immune-mediated tissue injury through diverse paracrine mechanisms. In KTx, several early-phase clinical trials have also tested the potential for ex vivo–expanded regulatory immune cell therapies to promote donor-specific tolerance and prevent or resolve allograft injury. Other promising DMRT, including adult stem/progenitor cells, stem cell–derived extracellular vesicles, and implantable hydrogels/biomaterials remain at varying preclinical stages of translation for these renal conditions. To date (2021), no DMRT has gained market approval for use in patients with RVD, SA-AKI, DKD, or KTx, and clinical trials demonstrating definitive, cost-effective patient benefits are needed. Nonetheless, exciting progress in understanding the disease-specific mechanisms of action of MSCs and other DMRT, coupled with increasing knowledge of the pathophysiologic basis for renal-tissue injury and the experience gained from pioneering early-phase clinical trials provide optimism that influential, regenerative treatments for diverse kidney diseases will emerge in the years ahead.

Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR)

Yokota, Rodrigo — Thu, 07 Jan 2021 11:41:55 GMT-08:00

Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiologic functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by de novo and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene-encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathologic conditions, including kidney diseases. Excessive accumulation of glycosphingolipids and promotion of the ceramide salvage and sphingosine-1-phosphate (S1P) pathways are found in the damaged kidney. Acceleration of the sphingosine kinase/S1P/S1P receptor (SphK/S1P/S1PR) axis plays a central role in deteriorating kidney functions. The SphK/S1P/S1PR signaling impairment is also found during pregnancy complications, such as preeclampsia and intrauterine growth restriction (IUGR). This mini-review discusses the current state of knowledge regarding the role of sphingolipid metabolism on kidney diseases, and the possible involvement of preeclampsia and IUGR conditions.

Gut Microbiota-Immune System Interactions during Acute Kidney Injury

Noel, Sanjeev — Thu, 14 Jan 2021 01:27:37 GMT-08:00

Impact of Casein- versus Grain-Based Diets on Rat Renal Sodium Transporters’ Abundance and Regulation

McDonough, Alicia A. — Wed, 06 Jan 2021 01:46:58 GMT-08:00

Patients with Hepatorenal Syndrome Should Be Dialyzed? COMMENTARY

Regner, Kevin R. — Wed, 16 Dec 2020 11:33:50 GMT-08:00

Patients with Hepatorenal Syndrome Should Be Dialyzed? PRO

Velez, Juan Carlos Q. — Wed, 16 Dec 2020 11:33:50 GMT-08:00

Patients with Hepatorenal Syndrome Should Be Dialyzed? CON

Wadei, Hani M. — Wed, 16 Dec 2020 11:33:50 GMT-08:00

Persistent Isolated Hematuria in a Japanese Woman

Sato, Masayo — Thu, 25 Mar 2021 05:00:29 GMT-07:00

Purple Urine in a Patient with Refractory Hypotension

Sriperumbuduri, Sriram — Thu, 25 Mar 2021 05:00:29 GMT-07:00

Acute Kidney Injury in a Patient following Percutaneous Kidney Biopsy

Parmar, Malvinder S. — Thu, 25 Mar 2021 05:00:29 GMT-07:00

Does Whom Patients Sit Next to during Hemodialysis Affect Whether They Request a Living Donation?

Gillespie, Avrum — Fri, 15 Jan 2021 05:59:29 GMT-08:00

Social Networks in the Dialysis Unit: Can They Influence Patient Behavior?

Singh, Tripti — Thu, 25 Mar 2021 05:00:28 GMT-07:00

The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic Review

Chopra, Pavan — Thu, 07 Jan 2021 09:59:20 GMT-08:00

Adults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment–related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. SSRIs were the most studied type of drug and the evidence was largely insufficient. We found moderate SOE that long-term, high-dose vitamin D3 is ineffective for reducing depression severity. Cognitive behavioral therapy is more effective than (undefined) psychotherapy and placebo for depression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed. Systematic Review registry name and registration number: PROSPERO, CRD42020140227

Longitudinal Changes in the Use of PD Assistance for Patients Maintained on Peritoneal Dialysis

Fonseca-Correa, Jorge I. — Tue, 12 Jan 2021 12:46:30 GMT-08:00

Living Related Donor Kidney Transplantation in Atypical HUS: When Should It Be Considered?

Kurup, Meghna — Thu, 21 Jan 2021 09:30:12 GMT-08:00

Biomarkers in ANCA-Associated Vasculitis: Potential Pitfalls and Future Prospects

Morris, Adam D. — Tue, 19 Jan 2021 12:41:10 GMT-08:00

Over the past 3 decades, significant advancements in the understanding of the pathophysiology of ANCA-associated vasculitis has led to the development of a multitude of potential candidate biomarkers. Accompanied by the advent of increasingly effective therapeutic strategies, the need for a dependable biomarker to help determine the extent of disease activity and risk of relapse is ever present. Implementation of such a biomarker would enable tailored therapy, optimizing disease control while helping to mitigate unnecessary exposure to therapy and potential treatment-related damage. Although far from perfect, ANCA serology and B-cell population are the two main staple biomarker tools widely used in practice to help supplement clinical assessment. Over recent years, the application and progress of more novel biomarker tools have arisen in both organ-limited and multisystem disease, including genomics, urinary proteins, degradation products of the alternative complement system, cytokines, metabolomics, and biospectroscopy. Validation studies and clinical translation of these tools are required, with serial assessment of disease activity and determination of therapy according to biomarker status correlated with patient outcomes.

The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study

Raj, Dominic S. — Fri, 15 Jan 2021 01:28:43 GMT-08:00

Estimating Kidney Failure Risk Using Electronic Medical Records

Naranjo, Felipe S. — Wed, 06 Jan 2021 01:46:58 GMT-08:00

Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial

Agarwal, Rajiv — Fri, 15 Jan 2021 01:28:43 GMT-08:00

Mindfulness-based Virtual Reality Intervention in Hemodialysis Patients: A Pilot Study on End-user Perceptions and Safety

Hernandez, Rosalba — Fri, 08 Jan 2021 10:59:02 GMT-08:00

Steroid Regimen for Children with Nephrotic Syndrome Relapse

Williams, Anna Elizabeth — Thu, 21 Jan 2021 08:10:09 GMT-08:00

Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse

Kainth, Deepika — Thu, 21 Jan 2021 08:10:10 GMT-08:00

Variability in Culture-Negative Peritonitis Rates in Pediatric Peritoneal Dialysis Programs in the United States

Davis, T. Keefe — Mon, 18 Jan 2021 08:39:38 GMT-08:00

Opportunities for Improvement in Quality of Care of PD-Related Peritonitis in Children

Vidal, Enrico — Mon, 18 Jan 2021 08:39:38 GMT-08:00

Clinical Utility of Genetic Testing in the Precision Diagnosis and Management of Pediatric Patients with Kidney and Urinary Tract Diseases

Bekheirnia, Nasim — Fri, 30 Oct 2020 06:15:32 GMT-07:00

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Forster, Benjamin M. — Tue, 01 Dec 2020 10:20:45 GMT-08:00

Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney Failure

Bae, Sunjae — Thu, 25 Feb 2021 08:17:45 GMT-08:00

Time to Procurement and Post-Kidney Transplant Outcomes

Haakinson, Danielle J. — Fri, 26 Feb 2021 11:10:54 GMT-08:00

Correction: Infection-Related Acute Care Events among Patients with Glomerular Disease

American Society of Nephrology — Mon, 01 Mar 2021 06:01:35 GMT-08:00

Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria

Jardine, Meg — Mon, 22 Feb 2021 07:19:34 GMT-08:00

Life with Sickle Cell Disease and Kidney Failure

Couch, Sasha — Thu, 25 Feb 2021 08:31:19 GMT-08:00

Challenges with Providing Hospice Care for Patients Undergoing Long-Term Dialysis

Schell, Jane O. — Fri, 09 Oct 2020 08:50:46 GMT-07:00

Uric Acid and CKD Progression Matures with Lessons for CKD Risk Factor Discovery

Oluwo, Oluwaseun — Wed, 14 Oct 2020 08:51:07 GMT-07:00

Children with CKD Are Not Little Adults with CKD

Kula, Alexander J. — Thu, 15 Oct 2020 06:51:39 GMT-07:00

Resistant Hypertension in CKD

Thomas, George — Mon, 08 Feb 2021 09:47:52 GMT-08:00

Outcomes of Patients on Maintenance Dialysis Hospitalized with COVID-19

Chan, Lili — Fri, 30 Oct 2020 10:50:33 GMT-07:00

Preliminary Assessment of Acute Kidney Injury in Critically Ill Children Associated with SARS-CoV-2 Infection

Bjornstad, Erica C. — Tue, 03 Nov 2020 06:52:42 GMT-08:00

Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression

Mastrangelo, Antonio — Mon, 14 Dec 2020 08:31:23 GMT-08:00

GWAS-Based Discoveries in IgA Nephropathy, Membranous Nephropathy, and Steroid-Sensitive Nephrotic Syndrome

Sanchez-Rodriguez, Elena — Fri, 17 Jul 2020 07:54:21 GMT-07:00

Over the past decade, genome-wide association studies (GWAS) have emerged as a powerful tool to understand the genetic basis of complex traits in humans. The GWAS approach has been successfully applied to primary glomerular disorders, providing numerous novel insights into the genetic architecture of IgA nephropathy, membranous nephropathy, and steroid-sensitive nephrotic syndrome. IgA nephropathy appears to have a highly complex polygenic architecture, with nearly 20 genome-wide significant loci of small-to-moderate effects discovered to date. In contrast, the genetic susceptibility to membranous nephropathy and steroid-sensitive nephrotic syndrome appears to be driven by a small number of large-effect loci. The MHC locus on chromosome 6p21 is strongly associated with genetic susceptibility to all major types of immune-mediated glomerulopathies. However, a distinct set of classical HLA alleles is associated with each individual disease type, pinpointing to specific immune mechanisms underlying each of these conditions. Additional insights from the discovery of non-HLA risk loci reinforced the role of innate and adaptive immunity in the pathogenesis of these disorders, and highlighted important susceptibility overlaps between glomerular and other autoimmune and inflammatory conditions. Despite these initial successes, much larger GWAS and sequencing studies are still needed for each individual glomerular disease type. Increased power will be critical to comprehensively test for genetic effects across the full spectrum of allelic frequencies, to detect gene-gene and gene-environment interactions, and to potentially improve the performance of polygenic risk predictors. Moreover, the existing studies are limited mostly to European and East Asian populations, stressing the urgency to expand genetic discovery efforts to more diverse populations worldwide.

Acute Kidney Injury among Black Patients with Sickle Cell Trait and Sickle Cell Disease

Olaniran, Kabir O. — Mon, 01 Mar 2021 06:01:35 GMT-08:00

Pathophysiology and Treatment of Enteric Hyperoxaluria

Witting, Celeste — Tue, 08 Sep 2020 08:21:41 GMT-07:00

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative–sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and Medicare

Cashion, Winn — Thu, 18 Feb 2021 09:43:53 GMT-08:00

Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Treatment

Bolaños, Jonathan A. — Fri, 19 Feb 2021 10:57:44 GMT-08:00

Ambulatory Treatments for RAAS Inhibitor–Related Hyperkalemia and the 1-Year Risk of Recurrence

Hundemer, Gregory L. — Fri, 19 Feb 2021 10:46:54 GMT-08:00

The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation

Eerola, Verner — Fri, 26 Feb 2021 11:02:18 GMT-08:00

Deep Learning Model for Real-Time Prediction of Intradialytic Hypotension

Lee, Hojun — Thu, 11 Feb 2021 12:11:00 GMT-08:00

Patients with Protein-Truncating PKD1 Mutations and Mild ADPKD

Lanktree, Matthew B. — Thu, 18 Feb 2021 09:17:36 GMT-08:00

Nocturnal Systolic Hypertension and Adverse Prognosis in Patients with CKD

Wang, Qin — Wed, 10 Feb 2021 08:08:30 GMT-08:00

Acute Kidney Injury, Microvascular Rarefaction, and Estimated Glomerular Filtration Rate in Kidney Transplant Recipients

Doreille, Alice — Mon, 01 Mar 2021 06:01:34 GMT-08:00

Post-Kidney Transplant Care and Health Outcomes of US Veterans

Krishnan, Namrata — Thu, 18 Feb 2021 09:51:56 GMT-08:00

Preprint Servers in Kidney Disease Research

Vlasschaert, Caitlyn — Fri, 17 Jul 2020 07:54:21 GMT-07:00

Preprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on “late-breaking” information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.

Leveraging Deep Learning to Improve Safety of Outpatient Hemodialysis

Correa, Simon — Thu, 11 Feb 2021 12:21:07 GMT-08:00

Ensuring the Equitable Advancement of American Kidney Health—the Need to Account for Socioeconomic Disparities in the ESRD Treatment Choices Model

Reddy, Yuvaram N.V. — Wed, 30 Dec 2020 07:39:40 GMT-08:00

Separate and Unequal: Race-Based Algorithms and Implications for Nephrology

Schmidt, Insa M. — Thu, 28 Jan 2021 09:35:55 GMT-08:00

Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study

Zheng, Zihe — Mon, 18 Jan 2021 09:18:39 GMT-08:00

Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy

Wang, Yan-Na — Tue, 16 Feb 2021 08:29:16 GMT-08:00

Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

Chiba, Takuto — Fri, 29 Jan 2021 09:37:00 GMT-08:00

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

Isaka, Yoshitaka — Fri, 05 Feb 2021 11:37:45 GMT-08:00

Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium

Wan, Xuesi — Thu, 04 Feb 2021 08:54:27 GMT-08:00

In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

Ravindran, Aishwarya — Thu, 21 Jan 2021 10:45:06 GMT-08:00

Effect of Kidney Function on Relationships between Lifestyle Behaviors and Mortality or Cardiovascular Outcomes: A Pooled Cohort Analysis

Schrauben, Sarah J. — Fri, 05 Feb 2021 10:53:20 GMT-08:00

SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process Maintenance

Rogg, Manuel — Fri, 29 Jan 2021 09:37:01 GMT-08:00

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney

Abedini, Amin — Tue, 02 Feb 2021 11:20:56 GMT-08:00

Impairment of Proteasome Function in Podocytes Leads to CKD

Makino, Shin-ichi — Thu, 28 Jan 2021 09:35:55 GMT-08:00

A Randomized Clinical Trial of Anti–IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection

Doberer, Konstantin — Fri, 18 Dec 2020 11:57:35 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 26 Feb 2021 11:00:25 GMT-08:00

In Search of the Optimal Target for Phosphate Control: Episode 1

Wald, Ron — Fri, 05 Feb 2021 11:24:40 GMT-08:00

Glomerular Exostosin Deposits in Membranous Lupus Nephritis—a Dialogue

Hilhorst, Marc — Mon, 25 Jan 2021 07:55:48 GMT-08:00

Reflections of a Naïve Trainee to Barnes Jewish Hospital/Washington University in 1970—My First 25 Years

Morrison, Aubrey R. — Thu, 28 Jan 2021 09:35:54 GMT-08:00

Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study

Fishbane, Steven — Wed, 10 Feb 2021 08:13:45 GMT-08:00

Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the Disease

Rodriguez-Iturbe, Bernardo — Tue, 02 Feb 2021 11:20:56 GMT-08:00

Acute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.

Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study

Kim, Esther D. — Thu, 28 Jan 2021 09:35:55 GMT-08:00

From Infancy to Fancy: A Glimpse into the Evolutionary Journey of Podocytes in Culture

Agarwal, Shivangi — Tue, 22 Dec 2020 09:45:36 GMT-08:00

Podocytes are critical components of the filtration barrier and responsible for maintaining healthy kidney function. An assault on podocytes is generally associated with progression of chronic glomerular diseases. Therefore, podocyte pathophysiology is a favorite research subject for nephrologists. Despite this, podocyte research has lagged because of the unavailability of techniques for culturing such specialized cells ex vivo in quantities that are adequate for mechanistic studies. In recent years, this problem was circumvented by the efforts of researchers, who successfully developed several in vitro podocyte cell culture model systems that paved the way for incredible discoveries in the field of nephrology. This review sets us on a journey that provides a comprehensive insight into the groundbreaking breakthroughs and novel technologic advances made in the field of podocyte cell culture so far, beginning from its inception, evolution, and progression. In this study, we also describe in detail the pros and cons of different models that are being used to culture podocytes. Our extensive and exhaustive deliberation on the status of podocyte cell culture will facilitate researchers to choose wisely an appropriate model for their own research to avoid potential pitfalls in the future.

In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis

Saw, Jessica J. — Wed, 23 Dec 2020 02:00:03 GMT-08:00

Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to CKD

Schaub, Jennifer A. — Tue, 22 Dec 2020 09:45:36 GMT-08:00

The proximal tubule relies on oxidative mitochondrial metabolism to meet its energy needs and has limited capacity for glycolysis, which makes it uniquely susceptible to damage during AKI, especially after ischemia and anoxia. Under these conditions, mitochondrial ATP production is initially decreased by several mechanisms, including fatty acid–induced uncoupling and inhibition of respiration related to changes in the shape and volume of mitochondria. Glycolysis is initially insufficient as a source of ATP to protect the cells and mitochondrial function, but supplementation of tricarboxylic acid cycle intermediates augments anaerobic ATP production, and improves recovery of mitochondrial oxidative metabolism. Incomplete recovery is characterized by defects of respiratory enzymes and lipid metabolism. During the transition to CKD, tubular cells atrophy but maintain high expression of glycolytic enzymes, and there is decreased fatty acid oxidation. These metabolic changes may be amenable to a number of therapeutic interventions.

Meeting the Demand for Renal Replacement Therapy during the COVID-19 Pandemic: A Manufacturer’s Perspective

Anger, Michael S. — Tue, 29 Dec 2020 01:46:37 GMT-08:00

COVID-19 Antibodies and Outcomes among Outpatient Maintenance Hemodialysis Patients

Khatri, Minesh — Wed, 09 Dec 2020 02:28:11 GMT-08:00

Global Dialysis Perspective: Spain

Roca-Tey, Ramon — Wed, 30 Dec 2020 11:27:19 GMT-08:00

Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis

Tuttle, Katherine R. — Tue, 08 Dec 2020 01:29:19 GMT-08:00

A Transplant Patient with Blue Lips, Tongue, and Fingertips

Sriperumbuduri, Sriram — Thu, 25 Feb 2021 06:00:33 GMT-08:00

Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic Profiling

Chen, Wei — Fri, 04 Dec 2020 09:48:06 GMT-08:00

Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKD

Rosenberg, Stephanie — Wed, 30 Dec 2020 06:19:49 GMT-08:00

How To Prescribe And Troubleshoot Continuous Renal Replacement Therapy: A Case-Based Review

Neyra, Javier A. — Mon, 14 Dec 2020 09:25:45 GMT-08:00

Continuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient’s needs and the logistics available at the corresponding institution.

Unexpected Complication in an ESKD Patient during AVG Thrombectomy

Gill, Jasmeet — Thu, 25 Feb 2021 06:00:33 GMT-08:00

AKI in a Patient with Pyuria and an Alkaline Urine

Anthonissen, Blaise — Thu, 25 Feb 2021 06:00:33 GMT-08:00

Multidisciplinary Team versus a “Phosphate-Counting” App for Serum Phosphate Control: A Randomized Controlled Trial

Farfan-Ruiz, Ana Cecilia — Tue, 15 Dec 2020 01:29:55 GMT-08:00

Sedentary Behavior and Change in Kidney Function: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Hannan, Mary — Wed, 09 Dec 2020 02:28:11 GMT-08:00

Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney Injury

Motwani, Shveta S. — Tue, 29 Dec 2020 12:05:14 GMT-08:00

Development and Validation of a Web-Based Prediction Model for AKI after Surgery

Woo, Sang H. — Tue, 29 Dec 2020 01:46:37 GMT-08:00

Factors Associated with Dialysis Discontinuation Outside of the Acute Care Setting

Roberts, Matthew J. — Wed, 09 Dec 2020 02:28:11 GMT-08:00

A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKD

Nowak, Kristen L. — Fri, 04 Dec 2020 09:48:06 GMT-08:00

Novel Use of Premixed Dialysate Bags during Water Supply Interruption in Acute Hospital Setting

Kohn, Orly F. — Wed, 09 Dec 2020 09:54:50 GMT-08:00

Patients on dialysis are exposed to large amounts of water during conventional intermittent hemodialysis; hence, there are strict regulations regarding the quality of water used to prepare dialysate. Occasionally, water systems fail due to natural disasters or structural supply issues, such as water-main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to inpatients who are dependent on dialysis is essential, both from an ultrafiltration and a clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide KRT with premade, bagged dialysate to mitigate the effect on our patients on dialysis. This is a novel method using available machines and dialysate, which we normally stock for continuous KRT, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. Because this situation occurred in the midst of the SARS-CoV-2 pandemic, we had to be mindful of dialysate volumes and staffing time. Here, we present our investigation into the cause of the water-system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low-flow dialysate will not deliver the same Kt/V per session as standard dialysis; however, this method was successfully implemented and tailored with adjustments for patients requiring higher clearance for specific indications, such as severe hyperkalemia.

Inhibition of Lysyl Oxidase with β-aminopropionitrile Improves Venous Adaptation after Arteriovenous Fistula Creation

Hernandez, Diana R. — Fri, 18 Dec 2020 11:43:24 GMT-08:00

Low-dose Rituximab Monotherapy or in Combination with Tacrolimus Is Effective in Primary Membranous Nephropathy

Pathak, Vivek — Fri, 18 Dec 2020 09:28:45 GMT-08:00

The Impact of CKD on Perioperative Risk and Mortality after Bariatric Surgery

Carvalho Silveira, Flavia — Mon, 14 Dec 2020 06:09:39 GMT-08:00

Improving on the Adrogué–Madias Formula

Chen, Sheldon — Fri, 04 Dec 2020 01:38:27 GMT-08:00

The Adrogué–Madias (A-M) formula is correct as written, but technically, it only works when adding 1 L of an intravenous (IV) fluid. For all other volumes, the A-M algorithm gives an approximate answer, one that diverges further from the truth as the IV volume is increased. If 1 L of an IV fluid is calculated to change the serum sodium by some amount, then it was long assumed that giving a fraction of the liter would change the serum sodium by a proportional amount. We challenged that assumption and now prove that the A-M change in [sodium] ([Na]) is not scalable in a linear way. Rather, the Δ[Na] needs to be scaled in a way that accounts for the actual volume of IV fluid being given. This is accomplished by our improved version of the A-M formula in a mathematically rigorous way. Our equation accepts any IV fluid volume, eliminates the illogical infinities, and most importantly, incorporates the scaling step so that it cannot be forgotten. However, the nonlinear scaling makes it harder to obtain a desired Δ[Na]. Therefore, we reversed the equation so that clinicians can enter the desired Δ[Na], keeping the rate of sodium correction safe, and then get an answer in terms of the volume of IV fluid to infuse. The improved equation can also unify the A-M formula with the corollary A-M loss equation wherein 1 L of urine is lost. The method is to treat loss as a negative volume. Because the new equation is just as straightforward as the original formula, we believe that the improved form of A-M is ready for immediate use, alongside frequent [Na] monitoring.

Regional Citrate Anticoagulation Protocol for Patients with Presumed Absent Citrate Metabolism

Szamosfalvi, Balazs — Fri, 18 Dec 2020 01:56:30 GMT-08:00

Diagnostic Utility of Serial Microscopic Examination of the Urinary Sediment in Acute Kidney Injury

Varghese, Vipin — Fri, 11 Dec 2020 02:29:54 GMT-08:00

Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease

Bhutani, Gauri — Fri, 04 Dec 2020 01:38:27 GMT-08:00

Overview of The Human Heredity and Health in Africa Kidney Disease Research Network (H3A-KDRN)

Adu, Dwomoa — Tue, 08 Dec 2020 01:29:19 GMT-08:00

Resident Macrophages in Cystic Kidney Disease

Li, Zhang — Fri, 11 Dec 2020 10:08:43 GMT-08:00

Interstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well-studied inflammatory cell in the kidney, and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally, it was believed that renal macrophages were maintained from a constant supply of bone marrow–derived circulating monocytes, and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate-mapping methods, by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties on entering the kidney. The second, resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and properly respond to pathologic conditions, such as AKI, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.

The Relationship between APOL1 Structure and Function: Clinical Implications

Madhavan, Sethu M. — Wed, 04 Nov 2020 01:31:03 GMT-08:00

Common variants in the APOL1 gene are associated with an increased risk of nondiabetic kidney disease in individuals of African ancestry. Mechanisms by which APOL1 variants mediate kidney disease pathogenesis are not well understood. Amino acid changes resulting from the kidney disease–associated APOL1 variants alter the three-dimensional structure and conformational dynamics of the C-terminal α-helical domain of the protein, which can rationalize the functional consequences. Understanding the three-dimensional structure of the protein, with and without the risk variants, can provide insights into the pathogenesis of kidney diseases mediated by APOL1 variants.

Jump-Starting Kidney Research

Norton, Jenna M. — Mon, 10 Aug 2020 04:47:46 GMT-07:00

Metabolic Acidosis and CKD Progression

Madias, Nicolaos E. — Fri, 07 Aug 2020 12:27:56 GMT-07:00

PEXIVAS

De Vriese, An S. — Tue, 22 Sep 2020 12:25:26 GMT-07:00

Mind the Gap

Goldberg, Aviva M. — Tue, 19 Jan 2021 08:43:41 GMT-08:00

Social Determinants of Health and Race Disparities in Kidney Transplant

Wesselman, Hannah — Thu, 28 Jan 2021 01:37:03 GMT-08:00

Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United Kingdom

Plumb, Lucy A. — Tue, 19 Jan 2021 08:43:41 GMT-08:00

Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney Disease

Ahearn, Patrick — Tue, 26 Jan 2021 06:35:26 GMT-08:00

Advancing Nephrology

Braden, Gregory L. — Wed, 12 Aug 2020 05:47:51 GMT-07:00

New treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology—from value-based care to prize competitions—will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association–European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty’s and divisions’ educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology.

Is It Time for Precision Dialysis?

Gupta, Nupur — Fri, 18 Sep 2020 10:25:18 GMT-07:00

Characteristics of Acute Kidney Injury in Hospitalized COVID-19 Patients in an Urban Academic Medical Center

Lee, John R. — Fri, 18 Sep 2020 10:25:18 GMT-07:00

Prolonged SARS-CoV-2 Viral RNA Shedding and IgG Antibody Response to SARS-CoV-2 in Patients on Hemodialysis

Shaikh, Aisha — Wed, 14 Oct 2020 08:51:07 GMT-07:00

Barriers to Kidney Transplantation in Racial/Ethnic Minorities

Fox, Monica — Thu, 28 Jan 2021 01:51:58 GMT-08:00

APOL1 Nephropathy: From Genetics to Clinical Applications

Friedman, David J. — Thu, 02 Jul 2020 07:48:59 GMT-07:00

Rates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.

Use of Gadolinium in Individuals with Reduced Kidney Function

Kalantari, Kambiz — Mon, 11 Jan 2021 09:23:21 GMT-08:00

Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression

Heida, Judith E. — Wed, 27 Jan 2021 06:55:29 GMT-08:00

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States

Chang, Su-Hsin — Fri, 15 Jan 2021 06:58:50 GMT-08:00

Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival

Lan, James H. — Mon, 25 Jan 2021 07:53:46 GMT-08:00

Exome Chip Analyses and Genetic Risk for IgA Nephropathy among Han Chinese

Zhou, Xu-jie — Mon, 18 Jan 2021 08:39:38 GMT-08:00

Strategies to Reduce Rehospitalization in Patients with CKD and Kidney Failure

Doshi, Simit — Mon, 13 Jul 2020 06:59:20 GMT-07:00

Readmissions in patients with nondialysis-dependent CKD and kidney failure are common and are associated with significant morbidity, mortality, and economic consequences. In 2013, the Centers for Medicare and Medicaid Services implemented the Hospital Readmissions Reduction Program in an attempt to reduce high hospitalization-associated costs. Up to 50% of all readmissions are deemed avoidable and present an opportunity for intervention. We describe factors that are specific to the patient, the index hospitalization, and underlying conditions that help identify the “high-risk” patient. Early follow-up care, developing volume management strategies, optimizing nutrition, obtaining palliative care consultations for seriously ill patients during hospitalization and conducting goals-of-care discussions with them, instituting systematic advance care planning during outpatient visits to avoid unwanted hospitalizations and intensive treatment at the end of life, and developing protocols for patients with incident or prevalent cardiovascular conditions may help prevent avoidable readmissions in patients with kidney disease.

Assessing Genetic Risk for IgA Nephropathy

Prakash, Sindhuri — Mon, 18 Jan 2021 08:39:38 GMT-08:00

Correction: Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications

American Society of Nephrology — Wed, 06 Jan 2021 09:39:02 GMT-08:00

Effect of Sickle Cell Trait and APOL1 Genotype on the Association of Soluble uPAR with Kidney Function Measures in Black Americans

Reiner, Alexander P. — Wed, 02 Dec 2020 10:45:39 GMT-08:00

Optimizing Utilization of Kidneys from Hepatitis C–Positive Kidney Donors

Ariyamuthu, Venkatesh K. — Fri, 15 Jan 2021 06:58:50 GMT-08:00

Authors' Reply

Clarke, Candice L. — Tue, 29 Sep 2020 11:07:03 GMT-07:00

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

Lepa, Carolin — Wed, 30 Dec 2020 07:39:40 GMT-08:00

Remdesivir in COVID-19 Patients with Impaired Renal Function

Gevers, Sanna — Thu, 21 Jan 2021 10:45:06 GMT-08:00

Authors’ Reply

Adamsick, Meagan L. — Thu, 21 Jan 2021 10:45:07 GMT-08:00

Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study

De Meester, Johan — Thu, 05 Nov 2020 08:49:17 GMT-08:00

Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes

Reese, Peter P. — Tue, 15 Dec 2020 09:50:57 GMT-08:00

Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p

Haddad, George — Thu, 21 Jan 2021 10:45:07 GMT-08:00

Long-Term Exposure to Ambient PM2.5 and Increased Risk of CKD Prevalence in China

Li, Guoxing — Thu, 17 Dec 2020 07:15:33 GMT-08:00

Authors’ Reply

Denic, Aleksandar — Thu, 17 Dec 2020 07:15:34 GMT-08:00

Can Total Nephron Number Predict Progressive CKD after Radical Nephrectomy?

Seibel, Jean — Thu, 17 Dec 2020 07:15:34 GMT-08:00

Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated Rejection

Koenig, Alice — Wed, 25 Nov 2020 01:16:05 GMT-08:00

A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD

Toto, Robert — Mon, 07 Dec 2020 08:43:40 GMT-08:00

Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney Injury

Bugarski, Milica — Thu, 21 Jan 2021 10:45:07 GMT-08:00

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury

Gillis, Ellen E. — Wed, 06 Jan 2021 08:44:24 GMT-08:00

Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide Study

Fu, Edouard L. — Mon, 28 Dec 2020 09:08:14 GMT-08:00

Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy

Canney, Mark — Wed, 23 Dec 2020 08:27:25 GMT-08:00

Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study

Rehnberg, Johanna — Wed, 11 Nov 2020 10:18:24 GMT-08:00

Erratum

American Society of Nephrology — Fri, 29 Jan 2021 11:00:41 GMT-08:00

Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate

Chen, Yan — Wed, 25 Nov 2020 01:16:04 GMT-08:00

The Road Ahead for Research on Air Pollution and Kidney Disease

Al-Aly, Ziyad — Mon, 18 Jan 2021 09:18:38 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 29 Jan 2021 11:00:40 GMT-08:00

The Mineralocorticoid Receptor in Salt-Sensitive Hypertension and Renal Injury

Ayuzawa, Nobuhiro — Mon, 04 Jan 2021 09:13:31 GMT-08:00

Hypertension and its comorbidities pose a major public health problem associated with disease-associated factors related to a modern lifestyle, such high salt intake or obesity. Accumulating evidence has demonstrated that aldosterone and its receptor, the mineralocorticoid receptor (MR), have crucial roles in the development of salt-sensitive hypertension and coexisting cardiovascular and renal injuries. Accordingly, clinical trials have repetitively shown the promising effects of MR blockers in these diseases. We and other researchers have identified novel mechanisms of MR activation involved in salt-sensitive hypertension and renal injury, including the obesity-derived overproduction of aldosterone and ligand-independent signaling. Moreover, recent advances in the analysis of cell-specific and context-dependent mechanisms of MR activation in various tissues—including a classic target of aldosterone, aldosterone-sensitive distal nephrons—are now providing new insights. In this review, we summarize recent updates to our understanding of aldosterone-MR signaling, focusing on its role in salt-sensitive hypertension and renal injury.

Dysregulated Dynein-Mediated Trafficking of Nephrin Causes INF2-related Podocytopathy

Sun, Hua — Tue, 22 Dec 2020 05:54:56 GMT-08:00

Missing Self and DSA—Synergy of Two NK Cell Activation Pathways in Kidney Transplantation

Hidalgo, Luis G. — Thu, 07 Jan 2021 09:45:43 GMT-08:00

New ‘Antigens’ in Membranous Nephropathy

Sethi, Sanjeev — Wed, 30 Dec 2020 07:39:40 GMT-08:00

Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new “antigens.” This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)– and exotosin 2 (EXT2)–associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.

Animal Model of Pregnancy after Acute Kidney Injury Mirrors the Human Observations

Tangren, Jessica Sheehan — Wed, 06 Jan 2021 08:44:24 GMT-08:00

Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients

Hinze, Christian — Wed, 25 Nov 2020 01:16:05 GMT-08:00

The Arteriovenous Fistula and Progression of Kidney Disease

Golper, Thomas A. — Thu, 28 Jan 2021 05:00:28 GMT-08:00

Hypomagnesemia in the Cancer Patient

Workeneh, Biruh T. — Wed, 11 Nov 2020 01:24:25 GMT-08:00

Hypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.

Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: CON

Pun, Patrick H. — Thu, 03 Dec 2020 06:20:01 GMT-08:00

Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: PRO

Rodby, Roger A. — Thu, 03 Dec 2020 06:20:01 GMT-08:00

Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: COMMENTARY

Abu-Alfa, Ali K. — Thu, 03 Dec 2020 06:20:01 GMT-08:00

Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational Study

Raines, Nathan H. — Fri, 20 Nov 2020 01:23:35 GMT-08:00

Living behind the Mask amid Two Pandemics: COVID-19 and Social Injustice

Gee, Patrick O. — Tue, 08 Dec 2020 01:29:19 GMT-08:00

COVID-19 in Patients with CKD in New York City

Akchurin, Oleh — Thu, 26 Nov 2020 05:30:15 GMT-08:00

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19

Wang, Xiaoling — Tue, 01 Dec 2020 10:20:45 GMT-08:00

Effect of COVID-19 on Kidney Disease Incidence and Management

McAdams, Meredith — Tue, 24 Nov 2020 10:19:10 GMT-08:00

The COVID-19 outbreak has had substantial effects on the incidence and management of kidney diseases, including AKI, ESKD, GN, and kidney transplantation. Initial reports from China suggested a lower AKI incidence in patients with COVID-19, but more recent studies from North America reveal a much higher incidence, likely due to the higher prevalence of comorbid conditions, such as hypertension, diabetes, and CKD. AKI in this setting is associated with worse outcomes, including the requirement for vasopressors or mechanical ventilation and death. Performing RRT in those with AKI poses challenges, such as limiting exposure of staff, preserving PPE, coagulopathy, and hypoxemia due to acute respiratory distress syndrome. Continuous RRT is the preferred modality, with sustained low-efficiency dialysis also an option, both managed without 1:1 hemodialysis nursing support. Regional citrate is the preferred anticoagulation, but systemic unfractionated heparin may be used in patients with coagulopathy. The ultrafiltration rate has to be set carefully, taking into consideration hypotension, hypoxemia, and responsiveness to presser and ventilatory support. The chance of transmission puts in-center chronic hemodialysis and other immunosuppressed patients at particularly increased risk. Limited data show that patients with CKD are also at increased risk for more severe disease, if infected. Little is known about the virus’s effects on immunocompromised patients with glomerular diseases and kidney transplants, which introduces challenges for management of immunosuppressant regimens. Although there are no standardized guidelines regarding the management of immunosuppression, several groups recommend stopping the antimetabolite in hospitalized transplant patients and continuing a reduced dose of calcineurin inhibitors. This comprehensive review critically appraises the best available evidence regarding the effect of COVID-19 on the incidence and management of kidney diseases. Where evidence is lacking, current expert opinion and clinical guidelines are reviewed, and knowledge gaps worth investigation are identified.

Skin Rash in a Stage 4 CKD Patient Treated for Hyperkalemia

Boge, Hanna — Thu, 28 Jan 2021 05:00:28 GMT-08:00

Arteriovenous Fistula Creation and Estimated Glomerular Filtration Rate Decline in Advanced CKD: A Matched Cohort Study

Dupuis, Marie-Ève — Thu, 19 Nov 2020 01:38:50 GMT-08:00

Glomerular Filtration Function Decline, Mortality, and Cardiovascular Events: Data from the Strong Heart Study

Suchy-Dicey, Astrid M. — Thu, 26 Nov 2020 05:30:12 GMT-08:00

Association of Diet Quality Indices with Longitudinal Changes in Kidney Function in U.S. Hispanics/Latinos: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Missikpode, Celestin — Tue, 24 Nov 2020 10:19:10 GMT-08:00

Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions

Chancay, Jorge — Wed, 02 Dec 2020 10:33:24 GMT-08:00

An Unexpected Imaging Finding in a CKD Patient on Lithium Therapy

Anthonissen, Blaise — Thu, 28 Jan 2021 05:00:28 GMT-08:00

Kidney360: Year 1 in Review

Allon, Michael — Thu, 28 Jan 2021 05:00:28 GMT-08:00

CKD in a Patient Treated with Adefovir for Chronic Hepatitis B Virus Infection

Kudose, Satoru — Thu, 28 Jan 2021 05:00:28 GMT-08:00

The Δ Anion Gap/Δ Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?

Rudkin, Scott E. — Tue, 10 Nov 2020 10:18:39 GMT-08:00

Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients

Flannery, Alexander H. — Wed, 04 Nov 2020 09:28:08 GMT-08:00

Pathways Project: Development of a Multimodal Innovation To Improve Kidney Supportive Care in Dialysis Centers

Lupu, Dale E. — Mon, 23 Nov 2020 01:32:22 GMT-08:00

Current care models for older patients with kidney failure in the United States do not incorporate supportive care approaches. The absence of supportive care contributes to poor symptom management and unwanted forms of care at the end of life. Using an Institute for Healthcare Improvement Collaborative Model for Achieving Breakthrough Improvement, we conducted a focused literature review, interviewed implementation experts, and convened a technical expert panel to distill existing evidence into an evidence-based supportive care change package. The change package consists of 14 best-practice recommendations for the care of patients seriously ill with kidney failure, emphasizing three key practices: systematic identification of patients who are seriously ill, goals-of-care conversations with identified patients, and care options to respond to patient wishes. Implementation will be supported through a collaborative consisting of three intensive learning sessions, monthly learning and collaboration calls, site data feedback, and quality-improvement technical assistance. To evaluate the change package’s implementation and effectiveness, we designed a mixed-methods hybrid study involving the following: (1) effectiveness evaluation (including patient outcomes and staff perception of the effectiveness of the implementation of the change package); (2) quality-improvement monitoring via monthly tracking of a suite of quality-improvement indicators tied to the change package; and (3) implementation evaluation conducted by the external evaluator using mixed methods to assess implementation of the collaborative processes. Ten dialysis centers across the country, treating approximately 1550 patients, will participate. This article describes the process informing the intervention design, components of the intervention, evaluation design and measurements, and preliminary feasibility assessments.

Dietary Therapy for Managing Hyperphosphatemia

Narasaki, Yoko — Wed, 30 Dec 2020 07:10:55 GMT-08:00

Mobile Health in Dialysis: The Best Engagement Medium Is the One that’s with Patients

Singh, Karandeep — Tue, 22 Dec 2020 08:10:24 GMT-08:00

Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis

Assimon, Magdalene M. — Fri, 18 Dec 2020 08:59:26 GMT-08:00

Forever Starts Now

Kotwal, Sradha — Tue, 29 Dec 2020 08:13:41 GMT-08:00

Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury

Zhao, Min — Tue, 29 Dec 2020 08:13:40 GMT-08:00

Klotho in Clinical Nephrology

Neyra, Javier A. — Wed, 22 Jul 2020 10:03:26 GMT-07:00

αKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.

The Mobile Health Readiness of People Receiving In-Center Hemodialysis and Home Dialysis

Hussein, Wael F. — Tue, 22 Dec 2020 08:10:24 GMT-08:00

Long-Term Safety of Tolvaptan in ADPKD

Patel, Dipal M. — Tue, 29 Dec 2020 08:13:40 GMT-08:00

Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

Torres, Vicente E. — Tue, 29 Dec 2020 08:13:40 GMT-08:00

Effect of Phosphate-Specific Diet Therapy on Phosphate Levels in Adults Undergoing Maintenance Hemodialysis

St-Jules, David E. — Wed, 30 Dec 2020 07:10:55 GMT-08:00

Correction

American Society of Nephrology — Wed, 25 Nov 2020 01:28:53 GMT-08:00

NAT8 Variants, N-Acetylated Amino Acids, and Progression of CKD

Luo, Shengyuan — Wed, 30 Dec 2020 07:10:55 GMT-08:00

What Does Uromodulin Do?

Kipp, Anne — Mon, 24 Aug 2020 05:50:22 GMT-07:00

Prospective Cohort Study of Renin-Angiotensin System Blocker Usage after Hospitalized Acute Kidney Injury

Brar, Sandeep — Thu, 03 Dec 2020 09:20:24 GMT-08:00

Optimizing Peritoneal Dialysis–Associated Peritonitis Prevention in the United States

Perl, Jeffrey — Thu, 06 Aug 2020 12:05:06 GMT-07:00

Peritoneal dialysis (PD)–associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.

Addressing Polypharmacy in Outpatient Dialysis Units

Battistella, Marisa — Thu, 13 Aug 2020 11:13:49 GMT-07:00

Availability, Accessibility, and Quality of Conservative Kidney Management Worldwide

Lunney, Meaghan — Tue, 15 Dec 2020 07:48:19 GMT-08:00

Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract

Westland, Rik — Mon, 20 Apr 2020 04:58:25 GMT-07:00

Revolutions in genetics, epigenetics, and bioinformatics are currently changing the outline of diagnostics and clinical medicine. From a nephrologist’s perspective, individuals with congenital anomalies of the kidney and urinary tract (CAKUT) are an important patient category: not only is CAKUT the predominant cause of kidney failure in children and young adults, but the strong phenotypic and genotypic heterogeneity of kidney and urinary tract malformations has hampered standardization of clinical decision making until now. However, patients with CAKUT may benefit from precision medicine, including an integrated diagnostics trajectory, genetic counseling, and personalized management to improve clinical outcomes of developmental kidney and urinary tract defects. In this review, we discuss the present understanding of the molecular etiology of CAKUT and the currently available genome diagnostic modalities in the clinical care of patients with CAKUT. Finally, we discuss how clinical integration of findings from large-scale genetic, epigenetic, and gene-environment interaction studies may improve the prognosis of all individuals with CAKUT.

Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-19

Bowe, Benjamin — Mon, 16 Nov 2020 06:51:29 GMT-08:00

COVID-19 in Peritoneal Dialysis Patients

Jiang, Hua-Jun — Tue, 08 Sep 2020 08:21:41 GMT-07:00

Anticoagulation Strategies and Filter Life in COVID-19 Patients Receiving Continuous Renal Replacement Therapy

Shankaranarayanan, Divya — Thu, 17 Sep 2020 10:18:33 GMT-07:00

Walkaway PIRRT (as SLED) for Acute Kidney Injury

Burgner, Anna — Fri, 11 Sep 2020 07:07:30 GMT-07:00

Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease

Hanrahan, John P. — Wed, 16 Dec 2020 08:21:00 GMT-08:00

Incremental and Twice-Weekly Hemodialysis Program in Practice

Murea, Mariana — Tue, 22 Sep 2020 12:25:26 GMT-07:00

Patients with Kidney Disease: Ready to Use Smartphones for Health Care Delivery?

Schmidt, Lana — Tue, 22 Dec 2020 08:10:24 GMT-08:00

Gender and CKD

Ahmed, Sofia B. — Fri, 07 Aug 2020 12:27:56 GMT-07:00

A Model To Estimate Glucose Absorption in Peritoneal Dialysis: A Pilot Study

Kotla, Suman Krishna — Tue, 29 Sep 2020 10:36:18 GMT-07:00

Abnormal Imaging Findings of the Kidneys in a Patient with Shock

Luo, Xinyi — Thu, 31 Dec 2020 05:30:28 GMT-08:00

Patency of ePTFE Arteriovenous Graft Placements in Hemodialysis Patients: Systematic Literature Review and Meta-Analysis

Halbert, Ronald J. — Thu, 15 Oct 2020 09:15:37 GMT-07:00

Arteriovenous grafts (AVGs) are an appropriate option for vascular access in certain hemodialysis patients. Expanded polytetrafluoroethylene (ePTFE) has become the dominant material for such grafts, due in part to innovations in graft design and surgical interventions to reduce complications and improve patency rates. Comprehensive evidence syntheses have not been conducted to update AVG performance in an era in which both access choice and ePTFE graft functioning may have changed. We conducted a systematic review and meta-analysis summarizing outcomes from recent studies of ePTFE AVGs in hemodialysis, following PRISMA standards. Literature searches were conducted in multiple databases to identify observational and interventional studies of AVG patency and infection risk. Primary, primary-assisted, and secondary patency rates were analyzed at 6, 12, 18, and 24 months postplacement. Kaplan–Meier graft survival plots were digitized to recreate individual patient-level data. Patency rates were pooled using a random effects model. We identified 32 studies meeting our selection criteria that were published from 2004 through 2019. A total of 38 study arms of ePTFE grafts were included, representing 3381 AVG accesses placed. The mean primary, primary-assisted, and secondary patency rates at 1 year were 41% (95% CI, 35% to 47%), 46% (95% CI, 41% to 51%), and 70% (95% CI, 64% to 75%), respectively. Mean 24-month patency rates were 28% (95% CI, 22% to 33%), 34% (95% CI, 27% to 41%), and 54% (95% CI, 47% to 61%), respectively. A high degree of heterogeneity across studies was observed. Overall risk of infection was not consistently reported, but among available studies the pooled estimate was 9% per patient-year (95% CI, 6% to 12%). This meta-analysis provides an up-to-date estimate of the performance of ePTFE AVGs, within the context of improved graft designs and improved interventional techniques.

Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial

Charytan, David M. — Thu, 15 Oct 2020 09:15:37 GMT-07:00

Self-Referral Patterns of Living Kidney Donors via Social Media: Examining an Expanding Platform

Joachim, Emily — Thu, 31 Dec 2020 05:30:28 GMT-08:00

Induction and Donor Specific Antibodies in Low Immunologic Risk Kidney Transplant Recipients

Bath, Natalie M. — Thu, 01 Oct 2020 09:37:53 GMT-07:00

Severe Hypertension in a 3-Month-Old Infant

Chawla, Jonathan — Thu, 31 Dec 2020 05:30:28 GMT-08:00

Impact of Social Media on Self-Referral Patterns for Living Kidney Donation

DuBray, Bernard J. — Fri, 30 Oct 2020 09:26:53 GMT-07:00

Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial

Seliger, Stephen L. — Wed, 23 Sep 2020 09:50:08 GMT-07:00

Risk Factors for Kidney Stone Formation following Bariatric Surgery

Prochaska, Megan — Thu, 01 Oct 2020 09:37:53 GMT-07:00

Kidney stones are painful, common, and increasing in incidence. Obesity and bariatric surgery rates are also on the rise in the United States. Although bariatric surgery is associated with improvements in metabolic outcomes, malabsorptive bariatric surgery procedures are also associated with increased risk of kidney stones. Restrictive bariatric surgeries have not been associated with kidney-stone risk. Higher risk of kidney stones after malabsorptive procedures is associated with postsurgical changes in urine composition, including high urine oxalate, low urine citrate, and low urine volume. Certain dietary recommendations after surgery may help mitigate these urine changes and reduce risk of kidney stones. Understanding risk of kidney stones after surgery is essential to improving patient outcomes after bariatric surgery.

Back Pain and Lower Extremity Sensory Loss in an ESKD Patient

Maalouly, Christian — Thu, 31 Dec 2020 05:30:28 GMT-08:00

Cognitive Function and Uremic Toxins after Kidney Transplantation: An Exploratory Study

te Linde, Elsemieke — Mon, 21 Sep 2020 01:25:17 GMT-07:00

Dialysis Filter Life in COVID-19: Early Lessons from the Pandemic

Portales-Castillo, Ignacio — Thu, 31 Dec 2020 05:30:28 GMT-08:00

Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York City

Caplin, Nina J. — Fri, 16 Oct 2020 10:42:40 GMT-07:00

Psychosocial Impact of COVID-19 Pandemic on Patients with End-Stage Kidney Disease on Hemodialysis

Lee, Jacqueline — Tue, 20 Oct 2020 01:31:37 GMT-07:00

Characteristics, Outcomes and 60-Day Hospital Mortality of ICU Patients with COVID-19 and Acute Kidney Injury

Thakkar, Jyotsana — Fri, 02 Oct 2020 06:04:16 GMT-07:00

Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury

Wen, Yuang — Tue, 20 Oct 2020 10:00:12 GMT-07:00

Global Dialysis Perspective: South Africa

Jardine, Thabiet — Tue, 20 Oct 2020 10:00:12 GMT-07:00

APOL1 Risk Variants Impair Multiple Mitochondrial Pathways in a Metabolomics Analysis

Ma, Lijun — Wed, 30 Sep 2020 10:03:22 GMT-07:00

Beta-2 Microglobulin Amyloidosis: Past, Present, and Future

Portales-Castillo, Ignacio — Wed, 21 Oct 2020 11:24:32 GMT-07:00

Almost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of β-2 microglobulin (B2M). Within that period, substantial advances in RRT occurred. These improvements have led to a decrease in the incidence of DRA. In many countries, DRA is considered a “disappearing act” or complication. Although the prevalence of patients living with RRT increases, not all will have access to kidney transplantation. Consequently, the number of patients requiring interventions for treatment of DRA is postulated to increase. This postulate has been borne out in Japan, where the number of patients with ESKD requiring surgery for carpal tunnel continues to increase. Clinicians treating patients with ESKD have treatment options to improve B2M clearance; however, there is a need to identify ways to translate improved B2M clearance into improved quality of life for patients undergoing long-term dialysis.

Transcriptomes of Major Proximal Tubule Cell Culture Models

Khundmiri, Syed J. — Thu, 29 Oct 2020 09:51:15 GMT-07:00

Will Targeting Interleukin-6 in the Anemia of CKD Change Our Treatment Paradigm?

Coyne, Daniel W. — Thu, 03 Dec 2020 07:35:19 GMT-08:00

The Aftermath of AKI: Recurrent AKI, Acute Kidney Disease, and CKD Progression

Wen, Yumeng — Fri, 09 Oct 2020 11:47:01 GMT-07:00

This Month's Highlights

American Society of Nephrology — Tue, 29 Dec 2020 11:00:29 GMT-08:00

Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study

Hsu, Simon — Wed, 28 Oct 2020 07:18:33 GMT-07:00

Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease

Zhang, Chao — Mon, 12 Oct 2020 12:14:48 GMT-07:00

Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis

Kelly, Jaimon T. — Mon, 31 Aug 2020 06:41:38 GMT-07:00

Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults

Chin, Ho Jun — Mon, 09 Nov 2020 01:32:09 GMT-08:00

Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Pergola, Pablo E. — Thu, 03 Dec 2020 07:35:20 GMT-08:00

Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis

Ruiz-Rosado, Juan de Dios — Wed, 04 Nov 2020 05:53:01 GMT-08:00

Deep Learning–Based Segmentation and Quantification in Experimental Kidney Histopathology

Bouteldja, Nassim — Thu, 05 Nov 2020 08:49:17 GMT-08:00

Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

Arora, Veronica — Mon, 05 Oct 2020 07:54:37 GMT-07:00

Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance Hemodialysis

Chazot, Guillaume — Thu, 22 Oct 2020 01:26:42 GMT-07:00

Conventional and Genetic Evidence on the Association between Adiposity and CKD

Zhu, Pengfei — Fri, 30 Oct 2020 11:51:04 GMT-07:00

Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy

Devalaraja-Narashimha, Kishor — Mon, 07 Dec 2020 08:43:40 GMT-08:00

Complexities of eGFRs in a Study of Glomerular Physiology

Steiner, Robert W. — Mon, 09 Nov 2020 01:43:31 GMT-08:00

Authors’ Reply

Collard, Didier — Mon, 09 Nov 2020 01:43:31 GMT-08:00

Sphingosine-1-Phosphate Metabolism and Signaling in Kidney Diseases

Drexler, Yelena — Fri, 18 Dec 2020 11:57:35 GMT-08:00

In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.

Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity after Kidney Transplantation

Lepping, Rebecca J. — Fri, 16 Oct 2020 10:47:42 GMT-07:00

AKI in Hospitalized Patients with COVID-19

Chan, Lili — Thu, 03 Sep 2020 12:26:11 GMT-07:00

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19

Gupta, Shruti — Fri, 16 Oct 2020 10:47:43 GMT-07:00

COVID-19–Associated Glomerular Disease

Shetty, Aneesha A. — Thu, 19 Nov 2020 06:52:32 GMT-08:00

COVID-19–Associated Acute Kidney Injury: Learning from the First Wave

Wald, Ron — Wed, 28 Oct 2020 07:18:32 GMT-07:00

COVID-19 and APOL1: Understanding Disease Mechanisms through Clinical Observation

Friedman, David J. — Mon, 07 Dec 2020 08:43:40 GMT-08:00

Post-Mortem Diagnostics in COVID-19 AKI, More Often but Timely

Zijlstra, Jan G. — Thu, 05 Nov 2020 08:49:18 GMT-08:00

Authors’ Reply

Rosenstock, Jordan L. — Thu, 05 Nov 2020 08:49:16 GMT-08:00

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Schrauben, Sarah J. — Thu, 29 Oct 2020 09:51:16 GMT-07:00

The Relationship between AKI and CKD in Patients with Type 2 Diabetes: An Observational Cohort Study

Hapca, Simona — Fri, 18 Sep 2020 12:35:49 GMT-07:00

Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function

Denic, Aleksandar — Wed, 16 Sep 2020 11:55:34 GMT-07:00

Secular Changes in Mortality and Hospitalization over Time in People with Kidney Failure or Severe CKD as Compared with Other Noncommunicable Diseases

Tonelli, Marcello — Tue, 29 Sep 2020 11:07:03 GMT-07:00

Authors’ Reply

Akizawa, Tadao — Fri, 04 Sep 2020 09:16:32 GMT-07:00

Much to Fear about MUCH

Agarwal, Rajiv — Tue, 06 Oct 2020 10:25:15 GMT-07:00

Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney Disease

O’Hare, Ann M. — Thu, 06 Aug 2020 12:22:22 GMT-07:00

Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction

Huh, Sung-Ho — Tue, 04 Aug 2020 08:49:33 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 30 Oct 2020 10:00:32 GMT-07:00

Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis

Potluri, Vishnu S. — Fri, 11 Sep 2020 07:23:35 GMT-07:00

Authors’ Reply

Shin, Jung-Im — Fri, 11 Sep 2020 07:23:35 GMT-07:00

Prognostic Significance of Ambulatory BP Monitoring in CKD: A Report from the Chronic Renal Insufficiency Cohort (CRIC) Study

Rahman, Mahboob — Thu, 24 Sep 2020 01:40:37 GMT-07:00

A New Dimension to the Mechanisms Causing Muscle Loss in CKD

Price, S. Russ — Fri, 09 Oct 2020 11:47:02 GMT-07:00

Mechanisms Regulating Muscle Protein Synthesis in CKD

Zhang, Liping — Thu, 06 Aug 2020 12:22:23 GMT-07:00

Binder Blunder in CKD

Ix, Joachim H. — Fri, 11 Sep 2020 07:23:35 GMT-07:00

Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease

Casal Moura, Marta — Fri, 21 Aug 2020 07:56:25 GMT-07:00

Live Imaging of Monocyte Subsets in Immune Complex-Mediated Glomerulonephritis Reveals Distinct Phenotypes and Effector Functions

Turner-Stokes, Tabitha — Mon, 31 Aug 2020 06:41:39 GMT-07:00

Role of Roxadustat for ESA-Resistant Renal Anemia? —Read with Caution

Tanaka, Mototsugu — Fri, 04 Sep 2020 09:16:31 GMT-07:00

A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD)

Toussaint, Nigel D. — Fri, 11 Sep 2020 07:23:36 GMT-07:00

Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression

Brandt, Sabine — Fri, 28 Aug 2020 08:10:43 GMT-07:00

Extracellular Matrix Injury of Kidney Allografts in Antibody-Mediated Rejection: A Proteomics Study

Clotet-Freixas, Sergi — Tue, 08 Sep 2020 12:13:48 GMT-07:00

Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney

Marable, Sierra S. — Thu, 06 Aug 2020 12:22:26 GMT-07:00

Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE Trial

Oshima, Megumi — Wed, 30 Sep 2020 10:43:47 GMT-07:00

This Month's Highlights

American Society of Nephrology — Wed, 25 Nov 2020 10:00:27 GMT-08:00

A Single Point-in-Time eGFR Is Not Associated with Increased Risk of Dementia in the Elderly

Gupta, Aditi — Fri, 11 Sep 2020 07:23:36 GMT-07:00

Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals with CKD

Orlandi, Paula F. — Tue, 06 Oct 2020 10:25:16 GMT-07:00

Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis

Yamamoto, Shinya — Mon, 12 Oct 2020 12:14:49 GMT-07:00

Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy

Li, Ming — Thu, 10 Sep 2020 06:58:25 GMT-07:00

Short or Long Sleep Duration and CKD: A Mendelian Randomization Study

Park, Sehoon — Thu, 01 Oct 2020 07:14:50 GMT-07:00

Mix for Regeneration: Nephron Replacement by Transplanted Cells

Schmidt-Ott, Kai M. — Thu, 05 Nov 2020 08:49:17 GMT-08:00

Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury

Ning, Liang — Wed, 16 Sep 2020 11:55:34 GMT-07:00

Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal Crosstalk

Rudman-Melnick, Valeria — Wed, 28 Oct 2020 07:18:33 GMT-07:00

Murine Epsins Play an Integral Role in Podocyte Function

Wang, Ying — Tue, 13 Oct 2020 06:52:14 GMT-07:00

The Imposed Obscurity of Richard W. Lippman, MD (1916–1959), Revered Renal Researcher and Physician

Strauss, Franklin G. — Thu, 29 Oct 2020 09:51:15 GMT-07:00

Authors’ Reply

Kurella Tamura, Manjula — Fri, 11 Sep 2020 07:23:35 GMT-07:00

Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney Disease

Conway, Bryan R. — Fri, 25 Sep 2020 05:42:23 GMT-07:00

Death after Kidney Transplantation: An Analysis by Era and Time Post-Transplant

Ying, Tracey — Wed, 09 Sep 2020 07:36:13 GMT-07:00

Successful Introduction of Human Renovascular Units into the Mammalian Kidney

Pleniceanu, Oren — Tue, 04 Aug 2020 08:49:34 GMT-07:00

Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease

Sellmayr, Markus — Wed, 16 Sep 2020 11:55:34 GMT-07:00

A Comparison of Different Estimates of Albuminuria in Association with Mortality in Epidemiologic Research

Koopman, Jacob J.E. — Mon, 14 Sep 2020 07:53:03 GMT-07:00

Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m2

Bakris, George — Thu, 19 Nov 2020 06:44:08 GMT-08:00

Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD

Muanda, Flory T. — Wed, 25 Nov 2020 01:28:55 GMT-08:00

Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis

Aendekerk, Joop P. — Tue, 17 Nov 2020 12:26:04 GMT-08:00

Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy

Ghiggeri, Gian Marco — Mon, 30 Nov 2020 05:37:33 GMT-08:00

Depression Screening Tools for Patients with Kidney Failure

Kondo, Karli — Tue, 17 Nov 2020 12:26:05 GMT-08:00

Screening for Depression in People with Kidney Failure

Gregg, L. Parker — Tue, 17 Nov 2020 12:26:04 GMT-08:00

ACOs and Bending the Cost Curve for Health Care Spending for People with Kidney Failure

Awan, Ahmed A. — Tue, 24 Nov 2020 08:11:46 GMT-08:00

Infection-Related Acute Care Events among Patients with Glomerular Disease

Glenn, Dorey A. — Tue, 20 Oct 2020 11:06:04 GMT-07:00

Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients

Letellier, Thibault — Tue, 10 Nov 2020 06:07:35 GMT-08:00

Correction

American Society of Nephrology — Mon, 09 Nov 2020 11:46:46 GMT-08:00

Metabolic Alkalosis

Emmett, Michael — Thu, 25 Jun 2020 10:36:32 GMT-07:00

Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.

AKI!Now Initiative: Recommendations for Awareness, Recognition, and Management of AKI

Liu, Kathleen D. — Tue, 21 Apr 2020 04:51:19 GMT-07:00

The American Society of Nephrology has established a new initiative, AKI!Now, with the goal of promoting excellence in the prevention and treatment of AKI by building a foundational program that transforms education and delivery of AKI care, aiming to reduce morbidity and associated mortality and to improve long-term outcomes. In this article, we describe our current efforts to improve early recognition and management involving inclusive interdisciplinary collaboration between providers, patients, and their families; discuss the ongoing need to change some of our current AKI paradigms and diagnostic methods; and provide specific recommendations to improve AKI recognition and care. In the hospital and the community, AKI is a common and increasingly frequent condition that generates risks of adverse events and high costs. Unfortunately, patients with AKI may frequently have received less than optimal quality of care. New classifications have facilitated understanding of AKI incidence and its impact on outcomes, but they are not always well aligned with AKI pathophysiology. Despite ongoing research efforts, treatments to promote or hasten kidney recovery remain ineffective. To avoid progression, the current approach to AKI emphasizes the promotion of early recognition and timely response. However, a lack of awareness of the importance of early recognition and treatment among health care team members and the heterogeneity of approaches within the health care teams assessing the patient remains a major challenge. Early identification is further complicated by differences in settings where AKI occurs (the community or the hospital), and by differences in patient populations and cultures between the intensive care unit and ward environments. To address these obstacles, we discuss the need to improve education at all levels of care and to generate specific guidance on AKI evaluation and management, including the development of a widely applicable education and an AKI management toolkit, engaging hospital administrators to incorporate AKI as a quality initiative, and raising awareness of AKI as a complication of other disease processes.

Racial Disparities in the Arteriovenous Fistula Care Continuum in Hemodialysis Patients

Qian, Joyce — Tue, 20 Oct 2020 11:06:03 GMT-07:00

Genetic Disorders of the Glomerular Filtration Barrier

Li, Anna S. — Mon, 23 Mar 2020 05:27:10 GMT-07:00

The glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.

Depression: A Side Effect of CKD

Jones, Jennifer — Tue, 17 Nov 2020 12:26:04 GMT-08:00

Peritoneal Dialysis for Acute Kidney Injury during the COVID-19 Pandemic

Shimonov, Daniil — Fri, 14 Aug 2020 05:51:02 GMT-07:00

Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN)

Ito, Sadayoshi — Wed, 25 Nov 2020 01:28:54 GMT-08:00

Mineralocorticoid Receptor Antagonists for Diabetic Kidney Disease

Rossing, Peter — Wed, 25 Nov 2020 01:28:54 GMT-08:00

Are SGLT2 Inhibitors Safe and Effective in Advanced Diabetic Kidney Disease?

Zoungas, Sophia — Thu, 19 Nov 2020 06:44:08 GMT-08:00

The Role of Incremental Peritoneal Dialysis in the Era of the Advancing American Kidney Health Initiative

Reddy, Yuvaram N.V. — Fri, 24 Jul 2020 07:39:49 GMT-07:00

Stepping into the Void

Agarwal, Anupam — Thu, 09 Jul 2020 07:55:51 GMT-07:00

Advancing American Kidney Health (AAKH): Catalyst for Investment in Kidney Diseases Clinical Trials and Precision Medicine

Fowler, Kevin John — Wed, 05 Aug 2020 10:14:28 GMT-07:00

Accountable Care Organizations and Spending for Patients Undergoing Long-Term Dialysis

Bakre, Shivani — Tue, 24 Nov 2020 08:11:47 GMT-08:00

Prevalence of COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening

Rodríguez-Espinosa, Diana — Tue, 29 Sep 2020 11:07:02 GMT-07:00

Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients

Prendecki, Maria — Thu, 29 Oct 2020 09:51:14 GMT-07:00

Does SARS-CoV-2 Infect the Kidney?

Khan, Shaza — Tue, 13 Oct 2020 06:52:13 GMT-07:00

Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed Patients

King, Kristen L. — Fri, 09 Oct 2020 11:47:02 GMT-07:00

Long-Term Living Kidney Donor Risk: A Web-Based Calculator

Palzer, Elise F. — Fri, 30 Oct 2020 11:51:04 GMT-07:00

The Role of Telenephrology in the Management of CKD

Belcher, Justin M. — Mon, 21 Sep 2020 01:25:17 GMT-07:00

Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKD

Kimber, Cassandra — Fri, 04 Sep 2020 01:26:42 GMT-07:00

Characteristics and Effectiveness of Dedicated Care Programs for Patients Starting Dialysis: A Systematic Review

Attalla, Mirna — Tue, 08 Sep 2020 01:30:40 GMT-07:00

Global Perspectives in Dialysis: Singapore

Leo, Christopher Cheang Han — Fri, 18 Sep 2020 11:25:51 GMT-07:00

AKI and Hypercalcemia in a Patient with Weakness and Fatigue

Rahimi, Cheyenne — Wed, 25 Nov 2020 05:30:27 GMT-08:00

Interhospital Transfer and Outcomes in Patients with AKI: A Population-Based Cohort Study

Kitchlu, Abhijat — Thu, 17 Sep 2020 11:11:58 GMT-07:00

Long-Term Beneficial Effects of Tonsillectomy on Patients with Immunoglobulin A Nephropathy

Moriyama, Takahito — Wed, 02 Sep 2020 09:32:53 GMT-07:00

Renal Infarction in a Patient Found to Have a Dysproteinemia

Patel, Jayesh — Wed, 25 Nov 2020 05:30:27 GMT-08:00

Apparent AKI in a Patient with Ascites Following Laparoscopic Hysterectomy

Cervantes, Carmen Elena — Wed, 25 Nov 2020 05:30:27 GMT-08:00

A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC)

Quintero, Emily — Thu, 03 Sep 2020 01:28:00 GMT-07:00

Predictors of Arteriovenous Fistula Failure: A Post Hoc Analysis of the FAVOURED Study

See, Yong Pey — Mon, 14 Sep 2020 09:23:25 GMT-07:00

Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers

Lentine, Krista L. — Thu, 03 Sep 2020 08:30:09 GMT-07:00

Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective from the Spanish Nephrology

Sánchez-Alvarez, Emilio — Fri, 11 Sep 2020 09:31:44 GMT-07:00

Beware the Ides of March: A Fellow’s Perspective on Surviving the COVID-19 Pandemic

Hindi, Judy — Thu, 24 Sep 2020 01:29:45 GMT-07:00

The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UK

Kular, Dalvir — Thu, 10 Sep 2020 08:21:38 GMT-07:00

Global Dialysis Perspective: Guatemala

Garcia, Pablo — Thu, 17 Sep 2020 11:11:58 GMT-07:00

mTOR Signaling in Kidney Diseases

Gui, Yuan — Thu, 03 Sep 2020 09:46:01 GMT-07:00

The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, is crucial in regulating cell growth, metabolism, proliferation, and survival. Under physiologic conditions, mTOR signaling maintains podocyte and tubular cell homeostasis. In AKI, activation of mTOR signaling in tubular cells and interstitial fibroblasts promotes renal regeneration and repair. However, constitutive activation of mTOR signaling in kidneys results in the initiation and progression of glomerular hypertrophy, interstitial fibrosis, polycystic kidney disease, and renal cell carcinoma. Here, we summarize the recent studies about mTOR signaling in renal physiology and injury, and discuss the possibility of its use as a therapeutic target for kidney diseases.

Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: CON

Guthrie, Bruce — Wed, 23 Sep 2020 01:37:51 GMT-07:00

Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: COMMENTARY

Baker, Megan L. — Wed, 23 Sep 2020 01:37:51 GMT-07:00

Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: PRO

Barreto, Erin F. — Wed, 23 Sep 2020 01:37:51 GMT-07:00

Histopathologic and Clinical Features in Patients with Diabetes and Kidney Disease

Sanghavi, Sarah F. — Fri, 11 Sep 2020 07:13:38 GMT-07:00

Moving the Science of Patient-Reported Outcome Measures Forward

Ramer, Sarah J. — Thu, 22 Oct 2020 12:29:05 GMT-07:00

Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications

Poggio, Emilio D. — Thu, 15 Oct 2020 06:51:39 GMT-07:00

Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies

Halimi, Jean-Michel — Thu, 15 Oct 2020 06:51:39 GMT-07:00

How Safe Is a Native Kidney Biopsy?

Koirala, Abbal — Thu, 15 Oct 2020 06:51:39 GMT-07:00

Trends in Use and In-Hospital Outcomes of Subcutaneous Implantable Cardioverter Defibrillators in Patients Undergoing Long-Term Dialysis

Pun, Patrick H. — Wed, 23 Sep 2020 07:43:00 GMT-07:00

Utilization of Deep Learning for Subphenotype Identification in Sepsis-Associated Acute Kidney Injury

Chaudhary, Kumardeep — Thu, 08 Oct 2020 07:58:32 GMT-07:00

Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD

Chen, Jing — Tue, 06 Oct 2020 09:47:17 GMT-07:00

Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States

Hall, Rasheeda — Mon, 12 Oct 2020 07:26:52 GMT-07:00

Revisiting Filtration Fraction as an Index of the Risk of Hemofilter Clotting in Continuous Venovenous Hemofiltration

Hatamizadeh, Parta — Wed, 13 May 2020 07:48:48 GMT-07:00

The Curious Story of Cerebral Salt Wasting

Verbalis, Joseph G. — Wed, 01 Jul 2020 08:26:23 GMT-07:00

Association of VA Payment Reform for Dialysis with Spending, Access to Care, and Outcomes for Veterans with ESKD

Wang, Virginia — Tue, 22 Sep 2020 12:25:27 GMT-07:00

Effect of Urate-Lowering Therapy on Cardiovascular and Kidney Outcomes

Chen, Qi — Wed, 14 Oct 2020 08:51:08 GMT-07:00

Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving Hemodialysis

Ju, Angela — Thu, 22 Oct 2020 12:29:05 GMT-07:00

QT Interval in Adult with Chronic Hypokalemia due to Gitelman Syndrome

Courand, Pierre-Yves — Wed, 12 Aug 2020 05:47:51 GMT-07:00

Not All Sepsis-Associated Acute Kidney Injury Is the Same

Gunning, Samantha — Thu, 08 Oct 2020 07:58:32 GMT-07:00

Delivering High-Quality Peritoneal Dialysis

Teitelbaum, Isaac — Thu, 11 Jun 2020 07:10:24 GMT-07:00

Pain Management in a Patient with Kidney Failure

Moist, Louise — Fri, 10 Apr 2020 09:20:10 GMT-07:00

Health Policy for Dialysis Care in Canada and the United States

Tonelli, Marcello — Thu, 25 Jun 2020 10:36:32 GMT-07:00

Contemporary dialysis treatment for chronic kidney failure is complex, is associated with poor clinical outcomes, and leads to high health costs, all of which pose substantial policy challenges. Despite similar policy goals and universal access for their kidney failure programs, the United States and Canada have taken very different approaches to dealing with these challenges. While US dialysis care is primarily government funded and delivered predominantly by private for-profit providers, Canadian dialysis care is also government funded but delivered almost exclusively in public facilities. Differences also exist for regulatory mechanisms and the policy incentives that may influence the behavior of providers and facilities. These differences in health policy are associated with significant variation in clinical outcomes: mortality among patients on dialysis is consistently lower in Canada than in the United States, although the gap has narrowed in recent years. The observed heterogeneity in policy and outcomes offers important potential opportunities for each health system to learn from the other. This article compares and contrasts transnational dialysis-related health policies, focusing on key levers including payment, finance, regulation, and organization. We also describe how policy levers can incentivize favorable practice patterns to support high-quality/high-value, person-centered care and to catalyze the emergence of transformative technologies for alternative kidney replacement strategies.

Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease

Li, Jiahua — Tue, 09 Jun 2020 06:29:26 GMT-07:00

Diabetic kidney disease and its comorbid conditions, including atherosclerotic cardiovascular disease, heart failure, diabetes, and obesity, are interconnected conditions that compound the risk of kidney failure and cardiovascular mortality, and exponentiate health care costs. Sodium glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1 RA) are novel diabetes medications that prevent cardiovascular events and kidney failure. Clinical trials exploring the cardiovascular and kidney outcomes of SGLT2i and GLP-1 RA have fundamentally shifted the treatment paradigm of diabetes. Clinical guidelines for diabetes management recommend a more holistic approach beyond glycemic control and emphasize heart and kidney protection of SGLT2i and GLP-1 RA. However, the adoption of prescribing SGLT2i and GLP-1 RA for patients with diabetes and high cardiovascular and kidney risk has been slow. In this review, we provide a decision-making tool to help clinicians determine when to consider SGLT2i and GLP-1 RA for heart and kidney protection. First, we discuss a comprehensive risk assessment for patients with diabetic kidney disease. We compare the effectiveness of SGLT2i and GLP-1 RA for different risk categories. Then, we present a decision algorithm using cardiovascular and kidney failure risk stratification and the strength of current evidence for the use of SGLT2i and GLP-1 RA. Lastly, we review the adverse effects of SGLT2i and GLP-1 RA and propose mitigation strategies.

Fatigue While Undergoing Long-Term Hemodialysis

Sondergaard, Henning — Thu, 22 Oct 2020 12:29:05 GMT-07:00

Prevalence of Kidney Injury and Associations with Critical Illness and Death in Patients with COVID-19

Zheng, Xizi — Thu, 17 Sep 2020 10:18:33 GMT-07:00

Genome-Wide Association Studies of CKD and Related Traits

Tin, Adrienne — Thu, 14 May 2020 08:27:27 GMT-07:00

The past few years have seen major advances in genome-wide association studies (GWAS) of CKD and kidney function–related traits in several areas: increases in sample size from >100,000 to >1 million, enabling the discovery of >250 associated genetic loci that are highly reproducible; the inclusion of participants not only of European but also of non-European ancestries; and the use of advanced computational methods to integrate additional genomic and other unbiased, high-dimensional data to characterize the underlying genetic architecture and prioritize potentially causal genes and variants. Together with other large-scale biobank and genetic association studies of complex traits, these GWAS of kidney function–related traits have also provided novel insight into the relationship of kidney function to other diseases with respect to their genetic associations, genetic correlation, and directional relationships. A number of studies also included functional experiments using model organisms or cell lines to validate prioritized potentially causal genes and/or variants. In this review article, we will summarize these recent GWAS of CKD and kidney function–related traits, explain approaches for downstream characterization of associated genetic loci and the value of such computational follow-up analyses, and discuss related challenges along with potential solutions to ultimately enable improved treatment and prevention of kidney diseases through genetics.

Donor-Derived Cell-Free DNA: Is It All the Same? The Jury Is Still Out

Garg, Neetika — Mon, 21 Sep 2020 06:11:21 GMT-07:00

Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm

Lattanzio, Michael R. — Thu, 23 Jul 2020 02:20:07 GMT-07:00

Nearly seven decades have elapsed since the clinical and biochemical features of primary hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly because an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. These new concepts have emerged in all areas of this clinical condition, including identification, diagnosis, and treatment. Here, we review the recent advances in this field and summarize the effect these advances have on both diagnostic and therapeutic modalities.

Parathyroid Hormone Serum Levels and Mortality among Hemodialysis Patients in the Gulf Cooperation Council Countries: Results from the DOPPS (2012–2018)

Al Salmi, Issa — Wed, 26 Aug 2020 12:18:42 GMT-07:00

From Theory to Reality: Establishing a Successful Kidney Genetics Clinic in the Outpatient Setting

Lundquist, Andrew L. — Wed, 12 Aug 2020 09:27:27 GMT-07:00

The Nephrology Immersion Classroom for Internal Medicine Residents

Roberts, John K. — Thu, 20 Aug 2020 09:22:39 GMT-07:00

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers

Petropoulos, Zoe E. — Wed, 19 Aug 2020 01:29:34 GMT-07:00

Abdominal Distention in a Patient on Peritoneal Dialysis

Li, John Wing — Mon, 02 Nov 2020 09:20:40 GMT-08:00

Donor-Derived Cell Free DNA: Is It All the Same?

Melancon, Joseph K. — Fri, 19 Jun 2020 09:12:27 GMT-07:00

Calcimimetic Use in Dialysis-Dependent Medicare Fee-for-Service Beneficiaries and Implications for Bundled Payment

Gooding, Mark — Tue, 25 Aug 2020 01:28:18 GMT-07:00

Internal Medicine Residents’ Perceptions of Nephrology as a Career: A Focus Group Study

Beck, Natalie — Wed, 19 Aug 2020 01:29:34 GMT-07:00

How To Build a Successful Urgent-Start Peritoneal Dialysis Program

Rajora, Nilum — Tue, 11 Aug 2020 06:18:52 GMT-07:00

In-center hemodialysis (HD) remains the predominant dialysis therapy in patients with ESKD. Many patients with ESKD present in late stage, requiring urgent dialysis initiation, and the majority start HD with central venous catheters (CVCs), which are associated with poor outcomes and high cost of care. Peritoneal dialysis (PD) catheters can be safely placed in such patients with late-presenting ESKD, obviating the need for CVCs. PD can begin almost immediately in the recumbent position, using low fill volumes. Such PD initiations, commencing within 2 weeks of the catheter placement, are termed urgent-start PD (USPD). Most patients with an intact peritoneal cavity and stable home situation are eligible for USPD. Although there is a small risk of PD catheter–related mechanical complications, most can be managed conservatively. Moreover, overall outcomes of USPD are comparable to those with planned PD initiations, in contrast to the high rate of catheter-related infections and bacteremia associated with urgent-start HD. The ongoing coronavirus disease 2019 pandemic has further exposed the vulnerability of patients with ESKD getting in-center HD. PD can mitigate the risk of infection by reducing environmental exposure to the virus. Thus, USPD is a safe and cost-effective option for unplanned dialysis initiation in patients with late-presenting ESKD. To develop a successful USPD program, a strong infrastructure with clear pathways is essential. Coordination of care between nephrologists, surgeons or interventionalists, and hospital and PD center staff is imperative so that patient education, home visits, PD catheter placements, and urgent PD initiations are accomplished expeditiously. Implementation of urgent-start PD will help to increase PD use, reduce cost, and improve patient outcomes, and will be a step forward in fostering the goal set by the Advancing American Kidney Health initiative.

Functionally Essential Tubular Proteins Are Lost to Urine-Excreted, Large Extracellular Vesicles during Chronic Renal Insufficiency

Adam, Ryan J. — Tue, 25 Aug 2020 09:34:17 GMT-07:00

Assessing Polycystic Kidney Disease in Rodents: Comparison of Robotic 3D Ultrasound and Magnetic Resonance Imaging

Beaumont, Nathan J. — Tue, 18 Aug 2020 09:35:48 GMT-07:00

Polycystic kidney disease (PKD) is an inherited disorder characterized by renal cyst formation and enlargement of the kidney. PKD severity can be staged noninvasively by measuring total kidney volume (TKV), a promising biomarker that has recently received regulatory qualification. In preclinical mouse models, where the disease is studied and potential therapeutics are evaluated, the most popular noninvasive method of measuring TKV is magnetic resonance imaging (MRI). Although MRI provides excellent 3D resolution and contrast, these systems are expensive to operate, have long acquisition times, and, consequently, are not heavily used in preclinical PKD research. In this study, a new imaging instrument, based on robotic ultrasound (US), was evaluated as a complementary approach for assessing PKD in rodent models. The objective was to determine the extent to which TKV measurements on the robotic US scanner correlated with both in vivo and ex vivo reference standards (MRI and Vernier calipers, respectively). A cross-sectional study design was implemented that included both PKD-affected mice and healthy wild types, spanning sex and age for a wide range of kidney volumes. It was found that US-derived TKV measurements and kidney lengths were strongly associated with both in vivo MRI and ex vivo Vernier caliper measurements (R2=0.94 and 0.90, respectively). In addition to measuring TKV, renal vascular density was assessed using acoustic angiography (AA), a novel contrast-enhanced US methodology. AA image intensity, indicative of volumetric vascularity, was seen to have a strong negative correlation with TKV (R2=0.82), suggesting impaired renal vascular function in mice with larger kidneys. These studies demonstrate that robotic US can provide a rapid and accurate approach for noninvasively evaluating PKD in rodent models.

Organelle Stress and Crosstalk in Kidney Disease

Hasegawa, Sho — Fri, 07 Aug 2020 09:22:52 GMT-07:00

Organelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.

Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease

Besse, Whitney — Wed, 02 Sep 2020 09:32:53 GMT-07:00

Global Dialysis Perspective: India

Bharati, Joyita — Wed, 19 Aug 2020 09:34:22 GMT-07:00

Abdominal Pain and Fever in an Elderly Patient with Diabetes Mellitus

Khetan, Prakash — Thu, 29 Oct 2020 05:30:23 GMT-07:00

Global Dialysis Perspective: United States

Han, Yun — Fri, 14 Aug 2020 01:41:13 GMT-07:00

How Hemodialysis Patients Perceive the SARS-CoV-2 Health Crisis: Lessons from Austria

Davidovic, Tamara — Tue, 25 Aug 2020 09:34:17 GMT-07:00

Moving beyond COVID-19 Surge—Caring for Patients with Kidney Disease throughout the Pandemic

Belani, Sharina — Fri, 18 Sep 2020 06:01:48 GMT-07:00

Leveraging the Capabilities of the FDA’s Sentinel System To Improve Kidney Care

Adimadhyam, Sruthi — Mon, 19 Oct 2020 08:04:34 GMT-07:00

The Sentinel System is a national electronic postmarketing resource established by the US Food and Drug Administration to support assessment of the safety and effectiveness of marketed medical products. It has built a large, multi-institutional, distributed data network that contains comprehensive electronic health data, covering about 700 million person-years of longitudinal observation time nationwide. With its sophisticated infrastructure and a large selection of flexible analytic tools, the Sentinel System permits rapid and secure analyses, while preserving patient privacy and health-system autonomy. The Sentinel System also offers enhanced capabilities, including accessing full-text medical records, supporting randomized clinical trials embedded in healthcare delivery systems, and facilitating effective collection of patient-reported data using mobile devices, among many other research programs. The nephrology research community can use the infrastructure, tools, and data that this national resource offers for evidence generation. This review summarizes the Sentinel System and its ability to rapidly generate high-quality, real-world evidence; discusses the program’s experience in, and potential for, addressing gaps in kidney care; and outlines avenues for conducting research, leveraging this national resource in collaboration with Sentinel investigators.

COVID-19 Infection in ESKD: Findings from a Prospective Disease Surveillance Program at Dialysis Facilities in New York City and Long Island

Weiss, Steven — Mon, 19 Oct 2020 08:04:33 GMT-07:00

Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKI

Azam, Tariq U. — Tue, 22 Sep 2020 06:29:12 GMT-07:00

The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD Injury

Rutkowski, Mark Peter — Fri, 11 Sep 2020 07:23:36 GMT-07:00

The Mechanism of Kidney Disease Due to APOL1 Risk Variants

Pays, Etienne — Thu, 17 Sep 2020 10:20:54 GMT-07:00

Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection

Sise, Meghan E. — Tue, 25 Aug 2020 07:10:34 GMT-07:00

Moving Nephrology Genetics into Clinical Care

Lanktree, Matthew B. — Thu, 29 Oct 2020 05:30:22 GMT-07:00

Abnormal Kidney Ultrasound in a Transplant Patient with AKI

Sy-Go, Janina Paula T. — Thu, 29 Oct 2020 05:30:23 GMT-07:00

Authors' Reply

Farrington, Crystal — Mon, 06 Jul 2020 11:32:31 GMT-07:00

Gentamicin-Induced Acute Kidney Injury in an Animal Model Involves Programmed Necrosis of the Collecting Duct

Huang, Huihui — Wed, 08 Jul 2020 09:11:04 GMT-07:00

Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention Trial

Kurella Tamura, Manjula — Fri, 26 Jun 2020 07:17:32 GMT-07:00

Early Predictors of Arteriovenous Fistula Maturation: Preoperative Arterial Diameter Alone Is Not Enough

Zamboli, Pasquale — Mon, 06 Jul 2020 11:32:31 GMT-07:00

TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease

Rayego-Mateos, Sandra — Mon, 06 Jul 2020 11:32:31 GMT-07:00

Crucial Role of AIM/CD5L in the Development of Glomerular Inflammation in IgA Nephropathy

Takahata, Akiko — Wed, 01 Jul 2020 08:29:05 GMT-07:00

Kidney Disease-Associated APOL1 Variants Have Dose-Dependent, Dominant Toxic Gain-of-Function

Datta, Somenath — Thu, 16 Jul 2020 09:45:48 GMT-07:00

Domain-Specific Antibodies Reveal Differences in the Membrane Topologies of Apolipoprotein L1 in Serum and Podocytes

Gupta, Nidhi — Thu, 06 Aug 2020 12:22:25 GMT-07:00

Transcriptional Changes in Kidney Allografts with Histology of Antibody-Mediated Rejection without Anti-HLA Donor-Specific Antibodies

Callemeyn, Jasper — Wed, 08 Jul 2020 09:11:02 GMT-07:00

Erratum

American Society of Nephrology — Mon, 31 Aug 2020 10:00:32 GMT-07:00

Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes

Scales, Suzie J. — Thu, 06 Aug 2020 12:22:23 GMT-07:00

Association of Longitudinal Trajectories of Systolic BP with Risk of Incident CKD: Results from the Korean Genome and Epidemiology Study

Joo, Young Su — Wed, 05 Aug 2020 10:17:47 GMT-07:00

Could a Pragmatic Detection Strategy Be the Gateway for Effective Population Health for CKD?

Narva, Andrew S. — Mon, 24 Aug 2020 05:56:14 GMT-07:00

Nephropathic Cystinosis: A Distinct Form of CKD–Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23

Florenzano, Pablo — Mon, 06 Jul 2020 11:32:30 GMT-07:00

Amphiregulin Aggravates Glomerulonephritis via Recruitment and Activation of Myeloid Cells

Melderis, Simon — Thu, 02 Jul 2020 12:44:19 GMT-07:00

This Month's Highlights

American Society of Nephrology — Mon, 31 Aug 2020 10:00:32 GMT-07:00

Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease

Neumeier, Laura I. — Mon, 13 Jul 2020 11:02:23 GMT-07:00

Authors’ Reply

Kliger, Alan — Wed, 19 Aug 2020 07:29:39 GMT-07:00

Integration of GWAS Summary Statistics and Gene Expression Reveals Target Cell Types Underlying Kidney Function Traits

Li, Yong — Thu, 06 Aug 2020 12:22:24 GMT-07:00

Patterning a Ureter Is All in the Stroma

Little, Melissa H. — Fri, 21 Aug 2020 07:56:25 GMT-07:00

LIM-Nebulette Reinforces Podocyte Structural Integrity by Linking Actin and Vimentin Filaments

Ge, Xuhua — Fri, 31 Jul 2020 09:04:36 GMT-07:00

Sympathetic Overactivity in CKD Disrupts Buffering of Neurotransmission by Endothelium-Derived Hyperpolarizing Factor and Enhances Vasoconstriction

Cao, Wei — Thu, 02 Jul 2020 12:44:19 GMT-07:00

Critically Ill Patients with CKD Deserve Better Mortality Prediction Scores

Sanghavi, Sarah F. — Wed, 19 Aug 2020 07:29:39 GMT-07:00

Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation

Chen, Weiwei — Thu, 09 Jul 2020 07:56:55 GMT-07:00

Single-Cell RNA Sequencing Reveals mRNA Splice Isoform Switching during Kidney Development

Wineberg, Yishay — Fri, 10 Jul 2020 10:44:14 GMT-07:00

PKD1-Dependent Renal Cystogenesis in Human Induced Pluripotent Stem Cell-Derived Ureteric Bud/Collecting Duct Organoids

Kuraoka, Shohei — Mon, 03 Aug 2020 08:33:53 GMT-07:00

Rate and Predictors of Finding Monoclonal Gammopathy of Renal Significance (MGRS) Lesions on Kidney Biopsy in Patients with Monoclonal Gammopathy

Klomjit, Nattawat — Mon, 03 Aug 2020 08:33:52 GMT-07:00

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme

Sallam, May — Fri, 21 Aug 2020 07:56:25 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Wed, 30 Sep 2020 10:00:27 GMT-07:00

Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury

Chung, Jun-Jae — Fri, 10 Jul 2020 10:44:14 GMT-07:00

Two Tales of Single-Cell RNA Sequencing: Gene Expression and Alternative Splicing in Mouse Kidney Development

Chen, Lihe — Thu, 03 Sep 2020 12:26:12 GMT-07:00

Cell-Free DNA: Proceed, but with Caution

Crew, R. John — Mon, 10 Aug 2020 04:48:48 GMT-07:00

Use of Do-Not-Resuscitate Orders for Critically Ill Patients with ESKD

Danziger, John — Thu, 27 Aug 2020 07:33:43 GMT-07:00

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial

Witham, Miles D. — Thu, 13 Aug 2020 05:53:42 GMT-07:00

Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy

Midgley, Adam C. — Fri, 07 Aug 2020 10:51:02 GMT-07:00

Do-Not-Resuscitate Orders among Patients with ESKD Admitted to the Intensive Care Unit: A Bird’s Eye View

Scherer, Jennifer S. — Thu, 27 Aug 2020 07:33:42 GMT-07:00

Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program

Oshima, Megumi — Tue, 21 Jul 2020 02:54:18 GMT-07:00

Correction

American Society of Nephrology — Mon, 14 Sep 2020 07:53:03 GMT-07:00

Improving the Evaluation Process for Potential Living Kidney Donor Candidates

Franks, Karol — Thu, 24 Sep 2020 05:36:55 GMT-07:00

SGLT2 Inhibitors across the Spectrum of Severity of CKD

Ziaolhagh, Ali — Tue, 29 Sep 2020 11:35:11 GMT-07:00

IgE-Mediated Immune Response and Antibody-Mediated Rejection

Rascio, Federica — Wed, 09 Sep 2020 07:33:56 GMT-07:00

IgE in Antibody-Mediated Rejection

Adam, Benjamin A. — Wed, 09 Sep 2020 07:33:56 GMT-07:00

Artificial Intelligence

Hou, Jean — Wed, 16 Sep 2020 08:47:53 GMT-07:00

Donor Age, Donor-Recipient Size Mismatch, and Kidney Graft Survival

Lepeytre, Fanny — Tue, 25 Aug 2020 07:08:34 GMT-07:00

Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural Networks

Ligabue, Giulia — Wed, 16 Sep 2020 08:47:53 GMT-07:00

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories

Levin, Adeera — Tue, 29 Sep 2020 11:35:12 GMT-07:00

A RAND-Modified Delphi on Key Indicators to Measure the Efficiency of Living Kidney Donor Candidate Evaluations

Habbous, Steven — Thu, 24 Sep 2020 05:36:56 GMT-07:00

Performance of the Kidney Failure Risk Equation by Disease Etiology in Advanced CKD

Hundemer, Gregory L. — Mon, 14 Sep 2020 07:53:04 GMT-07:00

Cuffless Blood Pressure Monitoring

Pandit, Jay A. — Fri, 17 Jul 2020 07:54:22 GMT-07:00

Current BP measurements are on the basis of traditional BP cuff approaches. Ambulatory BP monitoring, at 15- to 30-minute intervals usually over 24 hours, provides sufficiently continuous readings that are superior to the office-based snapshot, but this system is not suitable for frequent repeated use. A true continuous BP measurement that could collect BP passively and frequently would require a cuffless method that could be worn by the patient, with the data stored electronically much the same way that heart rate and heart rhythm are already done routinely. Ideally, BP should be measured continuously and frequently during diverse activities during both daytime and nighttime in the same subject by means of novel devices. There is increasing excitement for newer methods to measure BP on the basis of sensors and algorithm development. As new devices are refined and their accuracy is improved, it will be possible to better assess masked hypertension, nocturnal hypertension, and the severity and variability of BP. In this review, we discuss the progression in the field, particularly in the last 5 years, ending with sensor-based approaches that incorporate machine learning algorithms to personalized medicine.

Acute Kidney Injury and Risk of CKD and Hypertension after Pediatric Cardiac Surgery

Zappitelli, Michael — Fri, 18 Sep 2020 10:25:18 GMT-07:00

Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of Life

Gjerde, Anna — Mon, 17 Aug 2020 07:03:53 GMT-07:00

The Histological Picture of Indication Biopsies in the First 2 Weeks after Kidney Transplantation

Van Loon, Elisabet — Mon, 10 Aug 2020 04:47:46 GMT-07:00

The Incidence, Risk Factors, and Prognosis of Acute Kidney Injury in Adult Patients with Coronavirus Disease 2019

Cheng, Yichun — Tue, 22 Sep 2020 12:25:27 GMT-07:00

COVID-19 in Children with Nephrotic Syndrome on Anti-CD20 Chronic Immunosuppression

Angeletti, Andrea — Fri, 10 Jul 2020 10:47:44 GMT-07:00

COVID-19–Associated Acute Kidney Injury

Siew, Edward D. — Tue, 22 Sep 2020 12:25:26 GMT-07:00

Management Consideration in Drug-Induced Lactic Acidosis

Morales, Alexander — Fri, 22 May 2020 05:48:44 GMT-07:00

Offering Better Standards of Dialysis Care for Immigrants

Cervantes, Lilia — Fri, 22 May 2020 05:48:44 GMT-07:00

Treatment of Granulomatosis with Polyangiitis and Microscopic Polyangiitis

Tesar, Vladimir — Fri, 29 May 2020 08:25:03 GMT-07:00

Can We Mend the Broken Clock by Timing Antihypertensive Therapy Sensibly?

Georgianos, Panagiotis I. — Mon, 11 May 2020 08:13:20 GMT-07:00

Clinical Genetic Screening in Adult Patients with Kidney Disease

Cocchi, Enrico — Thu, 09 Jul 2020 07:55:51 GMT-07:00

Expanded accessibility of genetic sequencing technologies, such as chromosomal microarray and massively parallel sequencing approaches, is changing the management of hereditary kidney diseases. Genetic causes account for a substantial proportion of pediatric kidney disease cases, and with increased utilization of diagnostic genetic testing in nephrology, they are now also detected at appreciable frequencies in adult populations. Establishing a molecular diagnosis can have many potential benefits for patient care, such as guiding treatment, familial testing, and providing deeper insights on the molecular pathogenesis of kidney diseases. Today, with wider clinical use of genetic testing as part of the diagnostic evaluation, nephrologists have the challenging task of selecting the most suitable genetic test for each patient, and then applying the results into the appropriate clinical contexts. This review is intended to familiarize nephrologists with the various technical, logistical, and ethical considerations accompanying the increasing utilization of genetic testing in nephrology care.

Toward Patient-Centered Innovation

Flythe, Jennifer E. — Fri, 10 Apr 2020 09:20:11 GMT-07:00

Individuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices.

Reversal of Donor Hepatitis C Virus–Related Mesangial Proliferative GN in a Kidney Transplant Recipient

Khairallah, Pascale — Wed, 16 Sep 2020 11:55:33 GMT-07:00

End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005–2014

Butler, Catherine R. — Wed, 09 Sep 2020 07:36:13 GMT-07:00

Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation

Louis, Kevin — Tue, 28 Jul 2020 10:45:12 GMT-07:00

COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes

Elias, Michelle — Wed, 26 Aug 2020 10:27:44 GMT-07:00

Correction

American Society of Nephrology — Wed, 30 Sep 2020 10:00:27 GMT-07:00

The Exclusion of Patients with CKD in Prospectively Registered Interventional Trials for COVID-19—a Rapid Review of International Registry Data

Major, Rupert — Tue, 08 Sep 2020 12:13:47 GMT-07:00

Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

Berling, Ingrid — Tue, 22 Sep 2020 06:29:13 GMT-07:00

Perspectives on COVID-19 from Singapore: Impact on ESKD Care and Medical Education

Coffman, Thomas M. — Tue, 18 Aug 2020 05:47:30 GMT-07:00

Improving Care for Patients after Hospitalization with AKI

Siew, Edward D. — Thu, 10 Sep 2020 06:58:25 GMT-07:00

Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome

Horinouchi, Tomoko — Thu, 16 Jul 2020 01:33:03 GMT-07:00

Fibrillary Glomerulonephritis and DnaJ Homolog Subfamily B Member 9 (DNAJB9)

Klomjit, Nattawat — Wed, 08 Jul 2020 09:45:26 GMT-07:00

Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12–24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.

Penile Pain in a Hemodialysis Patient

Cabrera Fermin, Clara Miguelina — Thu, 24 Sep 2020 05:30:22 GMT-07:00

A Systematic Approach To Promoting Home Hemodialysis during End Stage Kidney Disease

Lockridge, Robert — Wed, 08 Jul 2020 09:45:26 GMT-07:00

Home dialysis has garnered much attention since the advent of the Advancing American Kidney Health initiative. For many patients and nephrologists, home dialysis and peritoneal dialysis are synonymous. However, home hemodialysis (HHD) should not be forgotten. Since 2004, HHD has grown more rapidly than other dialytic modalities. The cardinal feature of HHD is customizability of treatment intensity, which can be titrated to address the vexing problems of volume and pressure loading during interdialytic gaps and ultrafiltration intensity during each hemodialysis session. Growing HHD utilization requires commitment to introducing patients to the modality throughout the course of ESKD. In this article, we describe a set of strategies for introducing HHD concepts and equipment. First, patients initiating dialysis may attend a transitional care unit, which offers an educational program about all dialytic modalities during 3–5 weeks of in-facility hemodialysis, possibly using HHD equipment. Second, prevalent patients on hemodialysis may participate in “trial-run” programs, which allow patients to experience increased treatment frequency and HHD equipment for several weeks, but without the overt commitment of initiating HHD training. In both models, perceived barriers to HHD—including fear of equipment, anxiety about self-cannulation, catheter dependence, and the absence of a care partner—can be addressed in a supportive setting. Third, patients on peritoneal dialysis who are nearing a transition to hemodialysis may be encouraged to consider a home-to-home transition (i.e., from peritoneal dialysis to HHD). Taken together, these strategies represent a systematic approach to growing HHD utilization in multiple phenotypes of patients on dialysis. With the feature of facilitating intensive hemodialysis, HHD can be a key not only to satiating demand for home dialysis, but also to improving the health of patients on dialysis.

Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy

Luzardo, Leonella — Fri, 07 Aug 2020 06:11:58 GMT-07:00

Unexpected FDG-PET Scan Finding in an ESKD Patient with Weight Loss

Ponlot, Eléonore — Thu, 24 Sep 2020 05:30:22 GMT-07:00

Single Lumen Alternating Micro-Batch Hemodiafiltration (SLAMB-HDF): A Device for Minimally Invasive Renal Replacement Therapy

Chawla, Lakhmir S. — Fri, 31 Jul 2020 10:21:53 GMT-07:00

Blood-based RRT, such as hemodialysis, requires access to the bloodstream and adequate blood flow to enable the requisite clearance. As such, nearly all RRT systems require two lumens, enabling a blood circuit that pulls blood from one lumen or needle and returns it via another lumen or needle. The proposed single lumen alternating micro-batch (SLAMB) technique uses a small single lumen to draw a “micro” batch of blood into a single reservoir. In the reservoir, the “batch” of blood is circulated at a high blood flow rate through a hemofilter or hemodialyzer, enabling efficient small- and middle-molecule clearance. Thereafter, the “purified” blood is returned to the patient and the cycle is repeated. Each batch comprises 20–300 ml of blood, which is adjusted to the vascular access, hemodynamic status, and size of the patient. Up to 15 cycles can be done per hour, allowing this system to achieve a blood clearance level comparable to modern continuous RRT systems. Because the system can function with a small-bore single lumen, this device can work with existing central lines, thus allowing for less invasive vascular access. Because of their size and relative simplicity, SLAMB-based systems are less expensive, smaller, and have improved portability. Lastly, a similar, manual SLAMB-hemofiltration kit, which requires no electricity or battery, can be developed at low cost (<$25) for use in austere medical conditions, thus expanding the availability of RRT for patients with AKI.

Sudden Coma and Quadriplegia in a Hemodialysis Patient

Yu, Chih-Hen — Thu, 24 Sep 2020 05:30:22 GMT-07:00

Elevated Plasma Free Sialic Acid Levels in Individuals with Reduced Glomerular Filtration Rates

Fuentes, Federico — Thu, 09 Jul 2020 10:01:15 GMT-07:00

Patency Outcomes of Arteriovenous Fistulas and Grafts for Hemodialysis Access: A Trade-Off between Nonmaturation and Long-Term Complications

Voorzaat, Bram M. — Thu, 23 Jul 2020 09:35:56 GMT-07:00

Approach to Persistent Microscopic Hematuria in Children

Kallash, Mahmoud — Fri, 10 Jul 2020 01:22:46 GMT-07:00

Persistent isolated microscopic hematuria is relatively common in pediatric practice, affecting around 0.25% of children. Isolated microscopic hematuria can be caused by a myriad of potentially benign or serious causes, including urologic issues; kidney stones; glomerular diseases, including disorders of the glomerular basement membrane; hematologic abnormalities; and others. The challenge for the pediatrician or pediatric nephrologist is to distinguish children with potentially progressive forms of kidney disease versus other causes while minimizing cost and inconvenience for the child and family. This manuscript will review the multiple potential causes of microscopic hematuria and provide a framework for the initial evaluation and monitoring of such patients.

The Geometry of Arteriovenous Fistulas Using Endothelial Nitric Oxide Synthase Mouse Models

Falzon, Isabelle — Fri, 31 Jul 2020 10:21:53 GMT-07:00

Hypoxia-Inducible Factor and Oxygen Biology in the Kidney

Sugahara, Mai — Wed, 22 Jul 2020 01:47:16 GMT-07:00

Kidney tissue hypoxia is detected in various kidney diseases and is considered to play an important role in the pathophysiology of both AKI and CKD. Because of the characteristic vascular architecture and high energy demand to drive tubular solute transport, the renal medulla is especially prone to hypoxia. Injured kidneys often present capillary rarefaction, inflammation, and fibrosis, which contribute to sustained kidney hypoxia, forming a vicious cycle promoting progressive CKD. Hypoxia-inducible factor (HIF), a transcription factor responsible for cellular adaptation to hypoxia, is generally considered to protect against AKI. On the contrary, consequences of sustained HIF activation in CKD may be either protective, neutral, or detrimental. The kidney outcomes seem to be affected by various factors, such as cell types in which HIF is activated/inhibited, disease models, balance between two HIF isoforms, and time and methods of intervention. This suggests multifaceted functions of HIF and highlights the importance of understanding its role within each specific context. Prolyl-hydroxylase domain (PHD) inhibitors, which act as HIF stabilizers, have been developed to treat anemia of CKD. Although many preclinical studies demonstrated renoprotective effects of PHD inhibitors in CKD models, there may be some situations in which they lead to deleterious effects. Further studies are needed to identify patients who would gain additional benefits from PHD inhibitors and those who may need to avoid them.

Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney Disease

Gallagher, Anna Rachel — Fri, 10 Jul 2020 01:22:46 GMT-07:00

Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: The Con View

Bobart, Shane A. — Mon, 13 Jul 2020 01:27:35 GMT-07:00

Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: Pro

Hogan, Jonathan J. — Mon, 13 Jul 2020 01:27:35 GMT-07:00

Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: Commentary

Glassock, Richard J. — Mon, 13 Jul 2020 01:27:35 GMT-07:00

Gerhard Giebisch and the Gift of Mentorship

Aronson, Peter S. — Tue, 21 Jul 2020 09:48:39 GMT-07:00

Global Dialysis Perspective: Vietnam

Pham Van, Bui — Tue, 21 Jul 2020 06:53:17 GMT-07:00

Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Prospective Observational Study

Hong, Susana — Thu, 09 Jul 2020 10:01:15 GMT-07:00

Shaping Up Mitochondria in Diabetic Nephropathy

Mise, Koki — Thu, 30 Jul 2020 10:36:47 GMT-07:00

Mitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.

Screening and Recognition of Chronic Kidney Disease in VA Health Care System Primary Care Clinics

Bansal, Shweta — Thu, 09 Jul 2020 10:01:15 GMT-07:00

Association of FGF23 with Incident Sepsis in Community-Dwelling Adults: A Cohort Study

Paul, Shejuti — Wed, 29 Jul 2020 05:51:20 GMT-07:00

Plasma Galactose-Deficient IgA1 and C3 and CKD Progression in IgA Nephropathy

Chen, Pei — Wed, 11 Sep 2019 05:09:39 GMT-07:00

Factors Associated with Nephrology Fellowship Program Fill Rates

Matchett, Caroline L. — Mon, 18 May 2020 12:58:57 GMT-07:00

A Step in the Right Direction

Schell, Jane Ogden — Tue, 25 Aug 2020 07:08:33 GMT-07:00

Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer

Weiner, Daniel E. — Tue, 25 Aug 2020 07:08:33 GMT-07:00

Genetic Testing Is Beneficial to the Entire Family

Verma, Meghna — Thu, 27 Aug 2020 07:22:45 GMT-07:00

Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation

Price, Anna M. — Tue, 25 Aug 2020 07:08:34 GMT-07:00

Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement

Hogan, Marie C. — Tue, 25 Aug 2020 07:08:32 GMT-07:00

Preimplantation Genetic Testing for Genetic Kidney Disease

Burke, Wylie — Thu, 27 Aug 2020 07:22:45 GMT-07:00

Contrast-Associated Acute Kidney Injury

Meraz-Muñoz, Alejandro — Mon, 24 Aug 2020 05:50:22 GMT-07:00

Arterial Mechanics following Living Kidney Donation

Peixoto, Aldo J. — Tue, 25 Aug 2020 07:08:34 GMT-07:00

Preimplantation Genetic Testing for Monogenic Kidney Disease

Snoek, Rozemarijn — Thu, 27 Aug 2020 07:22:45 GMT-07:00

Implementing a Patient-Reported Outcome Measure for Hemodialysis Patients in Routine Clinical Care

Evans, Jenna M. — Tue, 25 Aug 2020 07:08:33 GMT-07:00

Mycophenolate Mofetil Treatment of C3 Glomerulopathy

Peleg, Yonatan — Wed, 19 Aug 2020 07:28:50 GMT-07:00

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease

Caravaca-Fontán, Fernando — Wed, 19 Aug 2020 07:28:51 GMT-07:00

Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD

Womack, Rebecca — Tue, 21 Jul 2020 02:33:40 GMT-07:00

Therapeutic Plasma Exchange Using Membrane Plasma Separation

Ahmed, Sadiq — Mon, 20 Apr 2020 04:58:25 GMT-07:00

Therapeutic plasma exchange is a blood purification technique designed for the removal of large molecular weight toxins such as pathogenic antibodies and lipoproteins. Plasma exchange can be performed either by membrane separation or centrifugation. Centrifugal plasma exchange is more common in the United States, while membrane separation is more popular in Germany and Japan. The membrane separation technique is similar to the ultrafiltration procedures performed with a standard dialysis machine but in which the membrane’s pores are large enough to allow removal of all circulating molecules while retaining the cellular components. The current availability of plasma separation membranes compatible with CRRT systems has dramatically increased the potential for almost all nephrologists to perform these treatments. This review describes the membrane separation techniques available in the United States, the practical aspects of ordering and operating a membrane separation plasma exchange procedure, and its possible complications.

Updates in Diagnosis and Management of Preeclampsia in Women with CKD

Wiles, Kate — Thu, 02 Apr 2020 01:32:20 GMT-07:00

It is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preeclampsia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preeclampsia and superimposed preeclampsia. It discusses the pathogenesis of preeclampsia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preeclampsia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preeclampsia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.

Reimagining Institutional Research Training

Spruance, Victoria M. — Fri, 03 Apr 2020 06:00:09 GMT-07:00

Defining Early Recovery of Acute Kidney Injury

Duff, Stephen — Wed, 01 Apr 2020 07:10:21 GMT-07:00

Fibroblast Growth Factor 23 and the Last Mile

Gutiérrez, Orlando M. — Fri, 10 Apr 2020 09:20:10 GMT-07:00

The Use of Genomics to Drive Kidney Disease Drug Discovery and Development

Reilly, Dermot F. — Thu, 19 Mar 2020 08:35:42 GMT-07:00

As opposed to diseases such as cancer, autoimmune disease, and diabetes, identifying drugs to treat CKD has proven significantly more challenging. Over the past 2 decades, new potential therapeutic targets have been identified as genetically altered proteins involved in rare monogenetic kidney diseases. Other possible target genes have been implicated through common genetic polymorphisms associated with CKD in the general population. Significant challenges remain before translating these genetic insights into clinical therapies for CKD. This paper will discuss how genetic variants may be leveraged to develop drugs and will especially focus on those genes associated with CKD to exemplify the value and challenges in including genetic information in the drug development pipeline.

How We Manage Hypertension in a Patient with a Recent Stroke

Chang, Tara I. — Mon, 11 May 2020 08:13:20 GMT-07:00

COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement Therapy

Zhao, Rui — Tue, 14 Jul 2020 09:26:46 GMT-07:00

Postangiography Increases in Serum Creatinine and Biomarkers of Injury and Repair

Liu, Caroline — Mon, 24 Aug 2020 05:50:23 GMT-07:00

The Early Days

Roberts, Glenda V. — Wed, 29 Jul 2020 08:58:42 GMT-07:00

Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United Kingdom

Ibrahim, Maria — Mon, 20 Jul 2020 02:00:19 GMT-07:00

Early Detection of CKD: Implications for Low-Income, Middle-Income, and High-Income Countries

Tonelli, Marcello — Mon, 24 Aug 2020 05:56:14 GMT-07:00

CKD is common, costly, and associated with adverse health outcomes. Because inexpensive treatments can slow the rate of kidney function loss, and because CKD is asymptomatic until its later stages, the idea of early detection of CKD to improve outcomes ignites enthusiasm, especially in low- and middle-income countries where renal replacement is often unavailable or unaffordable. Available data and prior experience suggest that the benefits of population-based screening for CKD are uncertain; that there is potential for harms; that screening is not a wise use of resources, even in high-income countries; and that screening has substantial opportunity costs in low- and middle-income countries that offset its hypothesized benefits. In contrast, some of the factors that diminish the value of population-based screening (such as markedly higher prevalence of CKD in people with diabetes, hypertension, and cardiovascular disease, as well as high preexisting use of kidney testing in such patients) substantially increase the appeal of searching for CKD in people with known kidney risk factors (case finding) in high-income countries as well as in low- and middle-income countries. For both screening and case finding, detection of new cases is the easiest component; the real challenge is ensuring appropriate management for a chronic disease, usually for years or even decades. This review compares and contrasts the benefits, harms, and opportunity costs associated with these two approaches to early detection of CKD. We also suggest criteria (discussed separately for high-income countries and for low- and middle-income countries) to use in assessing when countries should consider case finding versus when they should consider foregoing systematic attempts at early detection and focus on management of known cases.

AKI in Hospitalized Patients with and without COVID-19: A Comparison Study

Fisher, Molly — Wed, 15 Jul 2020 12:55:08 GMT-07:00

Caution in Identifying Coronaviruses by Electron Microscopy

Miller, Sarah E. — Fri, 10 Jul 2020 10:44:14 GMT-07:00

Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort

Xia, Peng — Fri, 21 Aug 2020 07:56:26 GMT-07:00

Postmortem Kidney Pathology Findings in Patients with COVID-19

Santoriello, Dominick — Wed, 29 Jul 2020 09:04:12 GMT-07:00

Kidney and Lung ACE2 Expression after an ACE Inhibitor or an Ang II Receptor Blocker: Implications for COVID-19

Wysocki, Jan — Wed, 15 Jul 2020 12:55:08 GMT-07:00

Authors’ Reply

Farkash, Evan A. — Wed, 12 Aug 2020 05:49:14 GMT-07:00

Kidney Involvement in COVID-19: Need for Better Definitions

Delsante, Marco — Thu, 09 Jul 2020 07:56:55 GMT-07:00

Kidney Biopsy Findings in Patients with COVID-19

Kudose, Satoru — Fri, 17 Jul 2020 08:06:30 GMT-07:00

High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening

Clarke, Candice — Thu, 30 Jul 2020 11:56:33 GMT-07:00

COVID-19–Associated Kidney Injury: A Case Series of Kidney Biopsy Findings

Sharma, Purva — Mon, 13 Jul 2020 11:02:23 GMT-07:00

Histopathologic and Ultrastructural Findings in Postmortem Kidney Biopsy Material in 12 Patients with AKI and COVID-19

Golmai, Pouneh — Thu, 16 Jul 2020 09:45:49 GMT-07:00

Racial and Ethnic Disparities in Seasonal Influenza Vaccination among Dialysis Facilities in the United States

Danziger, John — Thu, 13 Aug 2020 05:53:41 GMT-07:00

Rationing Scarce Resources: The Potential Impact of COVID-19 on Patients with Chronic Kidney Disease

Silberzweig, Jeffrey — Wed, 15 Jul 2020 12:55:08 GMT-07:00

Molecular Mismatch—the Renaissance of HLA in Kidney Transplantation

Wiebe, Chris — Thu, 06 Aug 2020 12:22:24 GMT-07:00

Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study

Senev, Aleksandar — Thu, 06 Aug 2020 12:22:25 GMT-07:00

Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney Transplant

Malone, Andrew F. — Wed, 15 Jul 2020 12:55:09 GMT-07:00

Increasing Peritoneal Dialysis Use in Response to the COVID-19 Pandemic: Will It Go Viral?

Brown, Edwina A. — Mon, 03 Aug 2020 08:33:52 GMT-07:00

Genetic Analysis in Kidney Disease: Advancing Clinical Diagnosis and Research Discovery

Besse, Whitney — Thu, 27 Aug 2020 05:30:21 GMT-07:00

Apparent Treatment-Resistant Hypertension Assessed by Office and Ambulatory Blood Pressure in Chronic Kidney Disease—A Report from the Chronic Renal Insufficiency Cohort Study

Thomas, George — Wed, 24 Jun 2020 09:32:29 GMT-07:00

Supply and Distribution of Vascular Access Physicians in the United States: A Cross-Sectional Study

Lee, Shoou-Yih D. — Wed, 01 Jul 2020 06:00:11 GMT-07:00

Understanding the Link between Neighborhoods and Kidney Disease

Lapedis, Cathryn J. — Tue, 23 Jun 2020 01:24:05 GMT-07:00

Neighborhoods are where we live, learn, work, pray, and play. Growing evidence indicates that neighborhoods are an important determinant of health. The built features of our neighborhoods, such as the ways in which the streets are designed and connected and the availability of green spaces and transit stops, as well as the social features, such as the trust among neighbors and the perceptions of safety, may influence health through multiple pathways, such as access to important resources, psychosocial stress, and health behaviors. In particular, the extant literature consistently documents an association between neighborhood features and renal-associated conditions, such as cardiovascular disease, hypertension, diabetes, and obesity. There is also some evidence suggesting an association between neighborhood poverty and ESKD. The link between neighborhood and earlier stages of CKD, however, has been less clear, with most studies documenting no association. It may be that the neighborhood measures used in previous studies do not capture features of the neighborhood important for earlier stages of disease development and progression. It may also be that our current biomarkers (e.g., eGFR) and urine protein are not able to pick up very early forms of renal damage because of the kidney’s overall high reserve capacity. This paper critically reviews the state of the literature on neighborhood and renal disease, with recommendations for neighborhood measures in future research. Neighborhoods are designed, built, and informed by policy, and thus, they are amenable to intervention, making them a potentially powerful way to improve renal health and reduce health inequalities at the population level.

Initial Validation of a Machine Learning-Derived Prognostic Test (KidneyIntelX) Integrating Biomarkers and Electronic Health Record Data To Predict Longitudinal Kidney Outcomes

Chauhan, Kinsuk — Tue, 30 Jun 2020 06:07:28 GMT-07:00

Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease

Inoue, Reiko — Tue, 16 Jun 2020 01:31:23 GMT-07:00

Value of Immediate Post-Kidney Biopsy Ultrasound in Excluding Late Hemorrhagic Complications

Al-Balas, Alian — Tue, 23 Jun 2020 09:29:55 GMT-07:00

Beyond Panel-Based Testing: Exome Analysis Increases Sensitivity for Diagnosis of Genetic Kidney Disease

Wilson, Parker C. — Wed, 13 May 2020 01:27:03 GMT-07:00

REDUcing the burden of dialysis Catheter ComplicaTIOns: a National approach (REDUCCTION) – design and baseline results

Kotwal, Sradha — Tue, 02 Jun 2020 02:13:45 GMT-07:00

Cystic Kidneys in a Patient with Craniofacial Abnormalities

Tsao, Allison L. — Thu, 27 Aug 2020 05:30:21 GMT-07:00

Management of Anemia in Nondialysis Chronic Kidney Disease: Current Recommendations, Real-World Practice, and Patient Perspectives

Guedes, Murilo — Wed, 01 Jul 2020 06:00:11 GMT-07:00

In nondialysis CKD (ND-CKD), anemia is a multifactorial and complex condition in which several dysfunctions dynamically contribute to a reduction in circulating hemoglobin (Hb) levels in red blood cells. Anemia is common in CKD and represents an important and modifiable risk factor for poor clinical outcomes. Importantly, symptoms related to anemia, including reduced physical functioning and fatigue, have been identified as high priorities by patients with CKD. The current management of anemia in ND-CKD (i.e., parameters to initiate treatment, Hb and iron indexes targets, choice of therapies, and effect of treatment on clinical and patient-reported outcomes) remains controversial. In this review article, we explore the epidemiology of anemia in ND-CKD and revise current recommendations and controversies in its management. Exploring data from real-world clinical practices, particularly from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps), we highlight the current challenges to translating current recommendations to clinical practice, providing patients’ perspectives of anemia and how it affects their quality of life. Finally, we summarize recent advances in the field of anemia that may change the way this condition will be managed in the future.

Multi-Organ Infarction in a Patient Receiving Infliximab

Campbell, Dean — Thu, 27 Aug 2020 05:30:21 GMT-07:00

Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKD

Chevalier, Robert L. — Tue, 07 Jul 2020 10:12:04 GMT-07:00

There is greater than tenfold variation in nephron number of the human kidney at birth. Although low nephron number is a recognized risk factor for CKD, its determinants are poorly understood. Evolutionary medicine represents a new discipline that seeks evolutionary explanations for disease, broadening perspectives on research and public health initiatives. Evolution of the kidney, an organ rich in mitochondria, has been driven by natural selection for reproductive fitness constrained by energy availability. Over the past 2 million years, rapid growth of an energy-demanding brain in Homo sapiens enabled hominid adaptation to environmental extremes through selection for mutations in mitochondrial and nuclear DNA epigenetically regulated by allocation of energy to developing organs. Maternal undernutrition or hypoxia results in intrauterine growth restriction or preterm birth, resulting in low birth weight and low nephron number. Regulated through placental transfer, environmental oxygen and nutrients signal nephron progenitor cells to reprogram metabolism from glycolysis to oxidative phosphorylation. These processes are modulated by counterbalancing anabolic and catabolic metabolic pathways that evolved from prokaryote homologs and by hypoxia-driven and autophagy pathways that evolved in eukaryotes. Regulation of nephron differentiation by histone modifications and DNA methyltransferases provide epigenetic control of nephron number in response to energy available to the fetus. Developmental plasticity of nephrogenesis represents an evolved life history strategy that prioritizes energy to early brain growth with adequate kidney function through reproductive years, the trade-off being increasing prevalence of CKD delayed until later adulthood. The research implications of this evolutionary analysis are to identify regulatory pathways of energy allocation directing nephrogenesis while accounting for the different life history strategies of animal models such as the mouse. The clinical implications are to optimize nutrition and minimize hypoxic/toxic stressors in childbearing women and children in early postnatal development.

Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids

Imafuku, Tadashi — Wed, 03 Jun 2020 10:15:34 GMT-07:00

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection

Chaudhri, Imran — Mon, 22 Jun 2020 01:37:01 GMT-07:00

Urinary Sediment Microscopy in Acute Kidney Injury Associated with COVID-19

Hernandez-Arroyo, Cesar F. — Tue, 02 Jun 2020 02:13:45 GMT-07:00

Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New York

Fisher, Molly — Thu, 18 Jun 2020 09:50:03 GMT-07:00

Appearances Can Be Deceiving - Viral-like Inclusions in COVID-19 Negative Renal Biopsies by Electron Microscopy

Cassol, Clarissa A. — Tue, 30 Jun 2020 06:07:27 GMT-07:00

Technology, Telehealth, and Nephrology: The Time Is Now

Jain, Gaurav — Wed, 03 Jun 2020 10:15:34 GMT-07:00

Response to COVID-19 Infection in Hemodialysis Patients: An Australian Perspective

Polkinghorne, Kevan R. — Fri, 19 Jun 2020 09:12:27 GMT-07:00

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

O’Brien, Frank J. — Wed, 24 Jun 2020 01:26:36 GMT-07:00

Unusual Dialysis Catheter Location in a Transplant Patient

Via Reque Cortes, Daniela del Pilar — Thu, 27 Aug 2020 05:30:21 GMT-07:00

An Approach to Neurological Disorders in a Kidney Transplant Recipient

Meena, Priti — Tue, 16 Jun 2020 10:37:41 GMT-07:00

Kidney transplantation is the preferred treatment modality in patients with ESKD. However, there are associated complications that arise from immunosuppressive medications, infections, and associated comorbidities. Neurologic disorders frequently develop in patients who have received a kidney transplant, which in turn increases the associated morbidity and mortality. This review discusses the common neurologic disorders after kidney transplantation, including infections, cognitive decline, drug-related conditions, malignancy, seizure, and other neurologic complications.

Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease

Nowak, Kristen L. — Fri, 21 Feb 2020 07:05:01 GMT-08:00

Autosomal dominant polycystic kidney disease is characterized by progressive development and enlargement of kidney cysts, leading to ESKD. Because the kidneys are under high metabolic demand, it is not surprising that mounting evidence suggests that a metabolic defect exists in in vitro and animal models of autosomal dominant polycystic kidney disease, which likely contributes to cystic epithelial proliferation and subsequent cyst growth. Alterations include defective glucose metabolism (reprogramming to favor aerobic glycolysis), dysregulated lipid and amino acid metabolism, impaired autophagy, and mitochondrial dysfunction. Limited evidence supports that cellular kidney metabolism is also dysregulated in humans with autosomal dominant polycystic kidney disease. There are notable overlapping features and pathways among metabolism, obesity, and/or autosomal dominant polycystic kidney disease. Both dietary and pharmacologic-based strategies targeting metabolic abnormalities are being considered as therapies to slow autosomal dominant polycystic kidney disease progression and are attractive, particularly given the slowly progressive nature of the disease. Dietary strategies include daily caloric restriction, intermittent fasting, time-restricted feeding, a ketogenic diet, and 2-deoxy-glucose as well as alterations to nutrient availability. Pharmacologic-based strategies include AMP-activated kinase activators, sodium glucose cotransporter-2 inhibitors, niacinamide, and thiazolidenediones. The results from initial clinical trials targeting metabolism are upcoming and anxiously awaited within the scientific and polycystic kidney disease communities. There continues to be a need for additional mechanistic studies to better understand the role of dysregulated metabolism in autosomal dominant polycystic kidney disease and for subsequent translation to clinical trials. Beyond single-intervention trials focused on metabolic reprograming in autosomal dominant polycystic kidney disease, great potential also exists by combining metabolic-focused therapeutic approaches with compounds targeting other signaling cascades altered in autosomal dominant polycystic kidney disease, such as tolvaptan.

Ambulatory Blood Pressure Phenotypes in Adults Taking Antihypertensive Medication with and without CKD

Mwasongwe, Stanford E. — Thu, 26 Mar 2020 05:59:15 GMT-07:00

Association of Primary Care Involvement with Death or Hospitalizations for Patients Starting Dialysis

Silver, Samuel A. — Thu, 05 Mar 2020 06:30:38 GMT-08:00

Ambulatory BP Phenotypes and Their Association with Target Organ Damage and Clinical Outcomes in CKD

Georgianos, Panagiotis I. — Thu, 26 Mar 2020 05:59:15 GMT-07:00

Prognostic Value of Ambulatory Blood Pressure Load in Pediatric CKD

Lee, Jason — Wed, 11 Mar 2020 08:26:54 GMT-07:00

The Value of Primary Care Provider Involvement in the Care of Kidney Failure Patients on Dialysis

Ahmed, Salman — Thu, 05 Mar 2020 06:30:38 GMT-08:00

A Systematic Review and Jurisdictional Scan of the Evidence Characterizing and Evaluating Assisted Peritoneal Dialysis Models

Hofmeister, Mark — Wed, 18 Mar 2020 08:55:10 GMT-07:00

Association of Tubular Solute Clearance with Symptom Burden in Incident Peritoneal Dialysis

Wang, Ke — Mon, 09 Mar 2020 06:34:41 GMT-07:00

Trends and Outcomes with Kidney Failure from Antineoplastic Treatments and Urinary Tract Cancer in France

Mansouri, Imène — Fri, 06 Mar 2020 07:58:09 GMT-08:00

Nephrology Fellows’ and Program Directors’ Perceptions of Hospital Rounds in the United States

Boyle, Suzanne M. — Tue, 17 Mar 2020 11:23:43 GMT-07:00

Kidney Failure with Urinary Tract Cancers

Shah, Ankur — Fri, 06 Mar 2020 07:58:10 GMT-08:00

When Increase in Serum Creatinine Doesn’t Imply Kidney Damage

Fried, Linda — Fri, 28 Feb 2020 06:27:28 GMT-08:00

Klotho Gene in Human Salt-Sensitive Hypertension

Citterio, Lorena — Tue, 28 Jan 2020 11:10:20 GMT-08:00

Reproducibility of Deceased Donor Kidney Procurement Biopsies

Husain, S. Ali — Thu, 23 Jan 2020 07:59:44 GMT-08:00

Randomized, Controlled Trial of Tacrolimus and Prednisolone Monotherapy for Adults with De Novo Minimal Change Disease

Medjeral-Thomas, Nicholas Rhys — Fri, 17 Jan 2020 06:50:22 GMT-08:00

Reconciling Short- and Long-Term Outcomes of In-Hospital Cardiac Arrest in Patients undergoing Maintenance Dialysis

Hsu, Simon — Tue, 07 Jan 2020 07:34:31 GMT-08:00

In-Hospital Cardiac Arrest Resuscitation Practices and Outcomes in Maintenance Dialysis Patients

Starks, Monique Anderson — Tue, 07 Jan 2020 07:34:31 GMT-08:00

The National Kidney Registry

Syed, Bushra — Tue, 28 Jan 2020 11:10:18 GMT-08:00

What It Means to Live with Focal Segmental Glomerulosclerosis

Bressler, Kent — Thu, 30 Apr 2020 07:33:45 GMT-07:00

Ask and It Shall Be Given

Canetta, Pietro A. — Thu, 30 Apr 2020 07:33:45 GMT-07:00

Walking while Talking in Older Adults with Chronic Kidney Disease

Ho, Jim Q. — Fri, 06 Mar 2020 07:58:09 GMT-08:00

Circulating Uromodulin and Risk of Cardiovascular Events and Kidney Failure

Ponte, Belen — Tue, 14 Apr 2020 10:16:17 GMT-07:00

Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers

Carter, Simon A. — Thu, 30 Apr 2020 07:33:44 GMT-07:00

Benefits of Continuing RAAS Inhibitors in Advanced CKD

Gaudreault-Tremblay, Marie-Michèle — Mon, 06 Apr 2020 08:22:57 GMT-07:00

The Elusive Promise of Bioimpedance in Fluid Management of Patients Undergoing Dialysis

Davies, Simon J. — Wed, 29 Apr 2020 08:37:30 GMT-07:00

Bioimpedance Guided Fluid Management in Peritoneal Dialysis

Tian, Na — Wed, 29 Apr 2020 08:37:30 GMT-07:00

Trajectories of Serum Sodium on In-Hospital and 1-Year Survival among Hospitalized Patients

Chewcharat, Api — Wed, 25 Mar 2020 06:32:37 GMT-07:00

Pilot Study of Return of Genetic Results to Patients in Adult Nephrology

Nestor, Jordan G. — Thu, 16 Apr 2020 02:04:02 GMT-07:00

A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials

Shoaf, Susan E. — Thu, 02 Apr 2020 01:32:20 GMT-07:00

Effects of Intensive Blood Pressure Control in Patients with and without Albuminuria

Chang, Alex R. — Wed, 15 Jul 2020 12:02:46 GMT-07:00

Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia

Akizawa, Tadao — Tue, 28 Jul 2020 10:43:58 GMT-07:00

Intensive Blood Pressure Lowering Should Be the Goal for Most Individuals at High Risk of Cardiovascular Disease Irrespective of Albuminuria

Ascher, Simon B. — Wed, 15 Jul 2020 12:02:46 GMT-07:00

Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Wu, Jun — Fri, 22 May 2020 05:48:43 GMT-07:00

Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis

van Daalen, Emma E. — Tue, 28 Jul 2020 10:43:59 GMT-07:00

Drug Selection for Treating Hypertension in Dialysis Patients

Shafi, Tariq — Thu, 16 Jul 2020 07:30:40 GMT-07:00

External Validation of the International IgA Nephropathy Prediction Tool

Zhang, Junjun — Thu, 02 Jul 2020 07:49:00 GMT-07:00

Comparative Efficacy and Safety of BP-Lowering Pharmacotherapy in Patients Undergoing Maintenance Dialysis

Shaman, Ahmed M. — Thu, 16 Jul 2020 07:30:40 GMT-07:00

Keeping Up with the Times

Brix, Silke R. — Tue, 28 Jul 2020 10:43:59 GMT-07:00

Apixaban versus No Anticoagulation in Patients Undergoing Long-Term Dialysis with Incident Atrial Fibrillation

Mavrakanas, Thomas A. — Fri, 22 May 2020 05:48:45 GMT-07:00

Racial Differences in Risk Factors for Kidney Stone Formation

Zisman, Anna L. — Fri, 19 Jun 2020 10:04:56 GMT-07:00

Adverse Drug Effects in Patients with CKD

Perazella, Mark A. — Wed, 01 Jul 2020 08:26:23 GMT-07:00

Kidney Disease, Race, and GFR Estimation

Levey, Andrew S. — Mon, 11 May 2020 08:13:20 GMT-07:00

Assessment of GFR is central to clinical practice, research, and public health. Current Kidney Disease Improving Global Outcomes guidelines recommend measurement of serum creatinine to estimate GFR as the initial step in GFR evaluation. Serum creatinine is influenced by creatinine metabolism as well as GFR; hence, all equations to estimate GFR from serum creatinine include surrogates for muscle mass, such as age, sex, race, height, or weight. The guideline-recommended equation in adults (the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation) includes a term for race (specified as black versus nonblack), which improves the accuracy of GFR estimation by accounting for differences in non-GFR determinants of serum creatinine by race in the study populations used to develop the equation. In that study, blacks had a 16% higher average measured GFR compared with nonblacks with the same age, sex, and serum creatinine. The reasons for this difference are only partly understood, and the use of race in GFR estimation has limitations. Some have proposed eliminating the race coefficient, but this would induce a systematic underestimation of measured GFR in blacks, with potential unintended consequences at the individual and population levels. We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group. We suggest full disclosure of use of race in GFR estimation, accommodation of those who decline to identify their race, and shared decision making between health care providers and patients. We also suggest mindful use of cystatin C as a confirmatory test as well as clearance measurements. It would be preferable to avoid specification of race in GFR estimation if there was a superior, evidence-based substitute. The goal of future research should be to develop more accurate methods for GFR estimation that do not require use of race or other demographic characteristics.

Adverse Drug Reactions in Patients with CKD

Laville, Solène M. — Wed, 01 Jul 2020 08:26:24 GMT-07:00

COVID-19 in Patients with Kidney Disease

Ajaimy, Maria — Tue, 07 Jul 2020 07:17:46 GMT-07:00

Long-Term Hemodialysis during the COVID-19 Pandemic

Gedney, Nieltje — Thu, 02 Jul 2020 07:49:00 GMT-07:00

Precision in GFR Reporting

Grubbs, Vanessa — Mon, 11 May 2020 08:13:20 GMT-07:00

I Love Nephrology, but Should I Be a Nephrologist?

Arora, Tanima — Tue, 12 May 2020 07:02:16 GMT-07:00

Careers in Critical Care Nephrology

Sanghavi, Sarah F. — Thu, 09 Jul 2020 07:55:51 GMT-07:00

Ensuring Gender-Affirming Care in Nephrology

Mohottige, Dinushika — Thu, 05 Mar 2020 06:30:38 GMT-08:00

At the Research-Clinical Interface

West, Kathleen M. — Mon, 10 Feb 2020 08:18:15 GMT-08:00

Whether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.

Presidential Address Kidney Week 2019

Rosenberg, Mark E. — Tue, 24 Mar 2020 07:47:32 GMT-07:00

The American Society of Nephrology Presidential Address was delivered by Mark Rosenberg at Kidney Week 2019 on November 7, 2019 in Washington, DC. The Address describes a remarkable alignment—a syzygy of policy, science, innovation accelerators, clinical trials, clinical care delivery, and activated patients—that exists today in the kidney space. As a community, we must ensure that the strategies developed to take advantage of this alignment, such as Advancing American Kidney Health, succeed. We must overcome our current challenges to thrive as a meaningful specialty. We have an incredible opportunity to come together as a kidney community to ensure success that realigns the priorities and incentives in kidney medicine to better achieve kidney health for all people throughout the world. The time is now to act.

Association of Race and Risk of Graft Loss among Kidney Transplant Recipients in the US Military Health System

Forman, Crystal J. — Thu, 30 Apr 2020 07:33:45 GMT-07:00

Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 2019

Husain, S. Ali — Mon, 18 May 2020 12:58:57 GMT-07:00

Use of Checkpoint Inhibitors in a Kidney Transplant Recipient with Metastatic Cancer

Ong, Song Ching — Mon, 23 Mar 2020 05:27:10 GMT-07:00

Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? PRO

De Broe, Marc E. — Wed, 17 Jun 2020 01:34:06 GMT-07:00

AKI in a Patient Engaged in Vegetable Juicing

Obadan, Odianosen I. — Thu, 30 Jul 2020 05:30:20 GMT-07:00

Renal Safety of Nonsteroidal Anti-Inflammatory Drugs and Opioids in Hospitalized Patients on Renin-Angiotensin System Inhibitors

Hung, Adriana M. — Thu, 30 Jul 2020 05:30:20 GMT-07:00

Interactions between FGF23 and Genotype in Autosomal Dominant Polycystic Kidney Disease

Grau, Laura — Tue, 12 May 2020 01:40:04 GMT-07:00

A Night Float System in Nephrology Fellowship: A Mixed Methods Evaluation

Plotkin, Jennifer B. — Fri, 08 May 2020 01:27:20 GMT-07:00

Janus-Faced: Molecular Mechanisms and Versatile Nature of Renal Fibrosis

Arai, Hiroyuki — Fri, 15 May 2020 09:56:42 GMT-07:00

Renal fibrosis is a major hallmark of CKD, regardless of the underlying etiology. In fibrosis development and progression, myofibroblasts play a pivotal role, producing extracellular matrix and interacting with various resident cells in the kidney. Over the past decade, the origin of myofibroblasts has been thoroughly investigated. Emerging evidence suggests that renal myofibroblasts originate from several cellular sources, including resident fibroblasts, pericytes, and bone marrow–derived cells. The contribution of resident fibroblasts is most crucial, and currently available data strongly suggest the importance of functional heterogeneity and plasticity of fibroblasts in kidney disease progression. Resident fibroblasts acquire distinct phenotypes based on their local microenvironment and exert multifactorial functions. For example, age-dependent alterations of renal fibroblasts make a significant contribution to the formation of tertiary lymphoid tissues, which promote local inflammation after injury in the aged kidney. In conjunction with fibrosis development, dysfunction of resident fibroblasts provokes unique pathologic conditions including renal anemia and peritubular capillary loss, both of which are major complications of CKD. Although renal fibrosis is considered detrimental in general, recent studies suggest it has beneficial roles, such as maintaining functional crosstalk with injured proximal tubular cells and supporting their regeneration. These findings provide novel insight into the mechanisms of renal fibrosis, which could be regarded as an adaptive process of kidney injury and repair. Precise understanding of the functional heterogeneity of resident fibroblasts and myofibroblasts has the potential to facilitate the development of novel therapeutics against kidney diseases. In this review, we describe the current perspective on the origin of myofibroblasts and fibroblast heterogeneity, with special emphasis on the dual aspects of renal fibrosis, both beneficial and detrimental, in CKD progression.

Incidence, Risk Factors, and Outcomes of Neonatal Renal Vein Thrombosis in Ontario: Population-Based Cohort Study

Ouellette, Allison C. — Wed, 27 May 2020 01:36:08 GMT-07:00

Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? CON

Wesseling, Catharina — Wed, 17 Jun 2020 01:34:06 GMT-07:00

Right Arm Pain and Swelling in an End-Stage Kidney Disease Patient

Jdiaa, Sara S. — Thu, 30 Jul 2020 05:30:20 GMT-07:00

Attitudes to Clinical Pig Kidney Xenotransplantation among Medical Providers and Patients

Padilla, Luz A. — Wed, 27 May 2020 01:36:08 GMT-07:00

Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? Commentary

Madero, Magdalena — Wed, 17 Jun 2020 01:34:06 GMT-07:00

No Zoom Required: Meeting at the β-Intercalated Cells

Lin, Wie-Yin — Thu, 23 Jul 2020 12:29:42 GMT-07:00

Fibroblast Growth Factor 23 and Risk of Hospitalization with Infection in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study

Ishigami, Junichi — Tue, 23 Jun 2020 08:10:25 GMT-07:00

Improving Equity in Medication Use through Better Kidney Function Measurement

Tuot, Delphine S. — Mon, 13 Jul 2020 11:02:23 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 31 Jul 2020 10:00:32 GMT-07:00

Impaired Renal HCO3- Excretion in Cystic Fibrosis

Berg, Peder — Thu, 23 Jul 2020 12:29:43 GMT-07:00

Mortality in US Hemodialysis Patients Following Exposure to Wildfire Smoke

Xi, Yuzhi — Thu, 16 Jul 2020 09:45:48 GMT-07:00

Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2–Dependent Mechanism in Polycystic Kidney Disease

Dwivedi, Nidhi — Wed, 17 Jun 2020 06:33:10 GMT-07:00

Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans

Collard, Didier — Tue, 16 Jun 2020 05:23:36 GMT-07:00

Long-Term Functional Patency and Cost-Effectiveness of Arteriovenous Fistula Creation under Regional Anesthesia: a Randomized Controlled Trial

Aitken, Emma — Fri, 24 Jul 2020 07:43:52 GMT-07:00

Distinct Modes of Balancing Glomerular Cell Proteostasis in Mucolipidosis Type II and III Prevent Proteinuria

Sachs, Wiebke — Wed, 08 Jul 2020 09:11:03 GMT-07:00

Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy

Sodhi, Komal — Thu, 25 Jun 2020 08:23:13 GMT-07:00

Obstructive Sleep Apnea, Other Sleep Characteristics, and Risk of CKD in the Atherosclerosis Risk in Communities Sleep Heart Health Study

Full, Kelsie M. — Fri, 26 Jun 2020 07:17:32 GMT-07:00

The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD

Shin, Jung-Im — Mon, 13 Jul 2020 11:02:22 GMT-07:00

Authors’ Reply

Weaver, Robert G. — Wed, 08 Jul 2020 09:11:02 GMT-07:00

The Effects of High-Protein Diets on Kidney Health and Longevity

Ko, Gang-Jee — Wed, 15 Jul 2020 12:55:09 GMT-07:00

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with—and perhaps without—impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.

Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental Glomerulosclerosis

Merchant, Michael L. — Fri, 19 Jun 2020 10:06:05 GMT-07:00

A Modest Proposal to Spur Innovation in Chronic Dialysis Care

Hostetter, Thomas H. — Tue, 16 Jun 2020 05:23:36 GMT-07:00

The Estimation Formula for the Urinary Albumin-Creatinine Ratio Based on the Protein-Creatinine Ratio Are Not Valid for a Kidney Transplant and a Living Donor Cohort

Jehn, Ulrich — Wed, 08 Jul 2020 09:11:04 GMT-07:00

Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model

Cai, Chuanqi — Thu, 25 Jun 2020 08:23:13 GMT-07:00

Striking a Balance in Simultaneous Heart Kidney Transplant: Optimizing Outcomes for All Wait-Listed Patients

Shaw, Brian I. — Thu, 04 Jun 2020 05:58:30 GMT-07:00

Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2

Farkash, Evan A. — Tue, 05 May 2020 05:45:03 GMT-07:00

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk Genotype

Wu, Huijuan — Fri, 19 Jun 2020 10:06:04 GMT-07:00

Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney Injury

Kow, Chia Siang — Wed, 01 Jul 2020 08:29:06 GMT-07:00

Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences

El Shamy, Osama — Tue, 16 Jun 2020 07:39:41 GMT-07:00

Epidemiology of COVID-19 in an Urban Dialysis Center

Corbett, Richard W. — Fri, 19 Jun 2020 10:06:04 GMT-07:00

COVID-19, Racism, and Racial Disparities in Kidney Disease: Galvanizing the Kidney Community Response

Crews, Deidra C. — Mon, 13 Jul 2020 11:02:22 GMT-07:00

This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2020_07_21_JASN2020060809.mp3

Authors’ Reply

Batlle, Daniel — Wed, 01 Jul 2020 08:29:06 GMT-07:00

Podocyte Integrin-β3 and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy

Madhusudhan, Thati — Fri, 24 Jul 2020 07:43:53 GMT-07:00

Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and Empagliflozin

Motrapu, Manga — Tue, 23 Jun 2020 08:10:24 GMT-07:00

Anemia and Incident End-Stage Kidney Disease

Saraf, Santosh L. — Wed, 20 May 2020 09:38:56 GMT-07:00

Global Dialysis Perspective: Argentina

Orias, Marcelo — Tue, 28 Apr 2020 09:39:51 GMT-07:00

Global Dialysis Perspective: Thailand

Kanjanabuch, Talerngsak — Fri, 24 Apr 2020 07:54:10 GMT-07:00

Effect of Renin-Angiotensin System Inhibitors on the Comparative Nephrotoxicity of NSAIDs and Opioids during Hospitalization

Miano, Todd A. — Mon, 27 Apr 2020 01:35:29 GMT-07:00

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series

Kumar, Dhiren — Mon, 27 Apr 2020 09:33:02 GMT-07:00

Strategies to Expand the Deceased Donor Pool for Pediatric Kidney Transplant Recipients

Kizilbash, Sarah J. — Fri, 15 May 2020 01:36:40 GMT-07:00

Fever and Gross Hematuria in a Kidney Transplant Recipient

Thorne, Peter — Thu, 30 Jul 2020 05:30:20 GMT-07:00

Frailty and the Potential Kidney Transplant Recipient: Time for a More Holistic Assessment?

Wu, Henry H.L. — Fri, 22 May 2020 09:26:36 GMT-07:00

Kidney Transplantation in Patients with HIV

Sawinski, Deirdre — Wed, 06 May 2020 01:43:10 GMT-07:00

Individuals with HIV are at increased risk for ESKD. Kidney transplantation is the best treatment for ESKD in the HIV+ population. Despite reduced access to transplantation, patients who are HIV+ have excellent outcomes and clearly benefit from receiving one. Common post-transplant complications and management concerns, including the optimal antiretroviral regimen, immunosuppression protocols, infectious prophylaxis, hepatitis C coinfection, metabolic complications, and malignancy are all discussed.

Foreign Perspective on Achieving a Successful Peritoneal Dialysis-First Program

Li, Philip Kam-Tao — Wed, 13 May 2020 01:27:03 GMT-07:00

CKRT Clotting and Cerebrovascular Accident in a Critically Ill Patient

Cervantes, Carmen Elena — Thu, 30 Jul 2020 05:30:20 GMT-07:00

COVID-19: A Home Dialysis Nurse Perspective

Bushey, Margaret — Thu, 04 Jun 2020 01:34:49 GMT-07:00

Acute Kidney Injury in the Time of COVID-19

Chan, Lili — Thu, 11 Jun 2020 09:42:44 GMT-07:00

Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New Orleans

Mohamed, Muner M.B. — Wed, 13 May 2020 10:16:30 GMT-07:00

End Points for Clinical Trials in Primary Hyperoxaluria

Milliner, Dawn S. — Thu, 12 Mar 2020 07:57:36 GMT-07:00

Patients with primary hyperoxaluria experience kidney stones from a young age and can develop progressive oxalate nephropathy. Progression to kidney failure often develops over a number of years, and is associated with systemic oxalosis, intensive dialysis, and often combined kidney and liver transplantation. There are no therapies approved by the Food and Drug Association. Thus, the Kidney Health Initiative, in partnership with the Oxalosis and Hyperoxaluria Foundation, initiated a project to identify end points for clinical trials. A workgroup of physicians, scientists, patients with primary hyperoxaluria, industry, and United States regulators critically examined the published literature for clinical outcomes and potential surrogate end points that could be used to evaluate new treatments. Kidney stones, change in eGFR, urine oxalate, and plasma oxalate were the strongest candidate end points. Kidney stones affect how patients with primary hyperoxaluria feel and function, but standards for measurement and monitoring are lacking. Primary hyperoxaluria registry data suggest that eGFR decline in most patients is gradual, but can be unpredictable. Epidemiologic data show a strong relationship between urine oxalate and long-term kidney function loss. Urine oxalate is reasonably likely to predict clinical benefit, due to its causal role in stone formation and kidney damage in CKD stages 1–3a, and plasma oxalate is likely associated with risk of systemic oxalosis in CKD 3b–5. Change in slope of eGFR could be considered the equivalent of a clinically meaningful end point in support of traditional approval. A substantial change in urine oxalate as a surrogate end point could support traditional approval in patients with primary hyperoxaluria type 1 and CKD stages 1–3a. A substantial change in markedly elevated plasma oxalate could support accelerated approval in patients with primary hyperoxaluria and CKD stages 3b–5. Primary hyperoxaluria type 1 accounts for the preponderance of available data, thus heavily influences the conclusions. Addressing gaps in data will further facilitate testing of promising new treatments, accelerating improved outcomes for patients with primary hyperoxaluria.

Secondary Hyperparathyroidism in a Patient with CKD

Hyder, Ryyan — Wed, 27 May 2020 07:35:57 GMT-07:00

Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis

Amoura, Ariane — Fri, 22 May 2020 05:48:44 GMT-07:00

The Importance of Kidney Medullary Tissue for the Accurate Diagnosis of BK Virus Allograft Nephropathy

Nankivell, Brian J. — Mon, 29 Jun 2020 04:21:53 GMT-07:00

Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan

Bargagli, Matteo — Thu, 11 Jun 2020 07:10:24 GMT-07:00

Dialysis Regret

Saeed, Fahad — Thu, 04 Jun 2020 05:59:34 GMT-07:00

The Electronic Medical Record and Nephrology Fellowship Education in the United States

Yuan, Christina M. — Tue, 23 Jun 2020 08:08:43 GMT-07:00

ADPKD, Tolvaptan, and Nephrolithiasis Risk

Hoorn, Ewout J. — Thu, 11 Jun 2020 07:10:25 GMT-07:00

Role of Skeletal Muscle Mitochondrial Dysfunction in CKD

Ryan, Alice S. — Fri, 26 Jun 2020 07:25:19 GMT-07:00

JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy

Tao, Jianling — Thu, 30 Apr 2020 07:33:44 GMT-07:00

Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome

Mason, Anna E. — Tue, 21 Apr 2020 04:51:20 GMT-07:00

Mortality and Recovery Associated with Kidney Failure due to Acute Kidney Injury

Shah, Silvi — Wed, 17 Jun 2020 06:44:42 GMT-07:00

Primary Hyperoxaluria

Lawrence, Jennifer E. — Thu, 12 Mar 2020 07:57:36 GMT-07:00

Individualizing Treatment of Steroid-Resistant Nephrotic Syndrome

Bagga, Arvind — Mon, 29 Jun 2020 04:21:53 GMT-07:00

From Nihilism to Opportunity

Olson, Andrew P.J. — Tue, 23 Jun 2020 08:08:42 GMT-07:00

Considering Our Patients and Tempering Terminology

Ingelfinger, Julie R. — Thu, 25 Jun 2020 10:36:32 GMT-07:00

Correction

American Society of Nephrology — Tue, 09 Jun 2020 06:29:26 GMT-07:00

Short-Term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection

Degner, Kenna R. — Thu, 19 Mar 2020 09:36:56 GMT-07:00

Green Effluent in a Patient on Continuous Veno-venous Hemodiafiltration

Dias Gonçalves, Priscila — Thu, 28 May 2020 10:00:25 GMT-07:00

Facial Deformity in a Patient with Chronic Secondary Hyperparathyroidism

Dhont, Sebastiaan — Thu, 28 May 2020 10:00:25 GMT-07:00

Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKD

Gardner, John — Tue, 31 Mar 2020 01:29:42 GMT-07:00

Utility of Peritoneal Scintigraphy in Peritoneal Dialysis Patients: One Center Experience

Sosa Barrios, R. Haridian — Tue, 24 Mar 2020 02:22:15 GMT-07:00

Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology

George, Jacob — Thu, 02 Apr 2020 10:11:53 GMT-07:00

Use of Immune Checkpoint Inhibitors in End Stage Kidney Disease Patients, Single Center Experience and Review of the Literature

Hirsch, Jamie S. — Wed, 18 Mar 2020 08:02:50 GMT-07:00

Anti-Cancer Activity of PAK4/NAMPT Inhibitor and Programmed Cell Death Protein-1 Antibody in Kidney Cancer

Trott, Josephine F. — Fri, 27 Mar 2020 02:22:52 GMT-07:00

Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease

Chang, Tara I. — Tue, 31 Mar 2020 06:00:11 GMT-07:00

Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution

Do, Catherine — Wed, 15 Apr 2020 01:24:45 GMT-07:00

Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.

Use of Gadolinium-Based Contrast Agents in Patients with Severe Renal Impairment. Absence of Risk Versus Caution: A Nephrologist’s Perspective

Rudnick, Michael R. — Thu, 25 Jun 2020 05:30:20 GMT-07:00

Sildenafil Citrate Does Not Reprogram Risk of Hypertension and Chronic Kidney Disease in Offspring of Preeclamptic Pregnancies in the Dahl SS/Jr Rat

Turbeville, Hannah R. — Fri, 17 Apr 2020 08:35:12 GMT-07:00

Identification of Podocyte Cargo Proteins by Proteomic Analysis of Clathrin-Coated Vesicles

Groener, Marwin — Thu, 16 Apr 2020 01:40:02 GMT-07:00

Dexamethasone for Preventing Major Adverse Kidney Events following Cardiac Surgery: Post-Hoc Analysis to Identify Subgroups

Venugopal, Hema — Thu, 30 Apr 2020 06:13:33 GMT-07:00

Renal Manifestations of Common Variable Immunodeficiency

Caza, Tiffany N. — Tue, 21 Apr 2020 01:45:16 GMT-07:00

Refractory Proteinuria in a Patient with Lupus Nephritis

Oda, Yasuhiro — Thu, 25 Jun 2020 05:30:20 GMT-07:00

CT Scan Surprise in a Potential Kidney Donor

Singh, Prince — Thu, 25 Jun 2020 05:30:20 GMT-07:00

Association between NSAID Exposure and Kidney Function Decline in Primary Care Patients

Pai, Amy Barton — Tue, 07 Apr 2020 01:33:52 GMT-07:00

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease

Nowak, Kristen L. — Tue, 28 Apr 2020 09:39:51 GMT-07:00

Point-of-Care Ultrasound for Native Kidney Biopsies

Palacherla, Jithendranath — Mon, 27 Apr 2020 01:35:29 GMT-07:00

Sodium-Based Osmotherapy in Continuous Renal Replacement Therapy: a Mathematical Approach

Yee, Jerry — Wed, 26 Feb 2020 09:56:34 GMT-08:00

Cerebral edema, in a variety of circumstances, may be accompanied by states of hyponatremia. The threat of brain injury from hypotonic stress-induced astrocyte demyelination is more common when vulnerable patients with hyponatremia who have end stage liver disease, traumatic brain injury, heart failure, or other conditions undergo overly rapid correction of hyponatremia. These scenarios, in the context of declining urinary output from CKD and/or AKI, may require controlled elevations of plasma tonicity vis-à-vis increases of the plasma sodium concentration. We offer a strategic solution to this problem via sodium-based osmotherapy applied through a conventional continuous RRT modality: predilution continuous venovenous hemofiltration.

The Effect of Risk of Maturation Failure and Access Type on Arteriovenous Access-Related Costs among Hemodialysis Patients

Kosa, Sarah D. — Fri, 13 Mar 2020 01:41:04 GMT-07:00

Does Vascular Access Type Affect Access–Related Costs?

Thamer, Mae — Fri, 13 Mar 2020 01:41:04 GMT-07:00

Venous Thrombotic Events in ANCA-Associated Vasculitis: Incidence and Risk Factors

Isaacs, Bradley — Tue, 03 Mar 2020 08:11:32 GMT-08:00

Abdominal Pain in a Patient with Asymmetry

Weisinger, Jose R. — Thu, 30 Apr 2020 08:30:19 GMT-07:00

AKI in a Patient with Cerebral Toxoplasmosis

Patel, Jayesh — Thu, 30 Apr 2020 08:30:19 GMT-07:00

Abdominal Pain in a Patient with Hypercalcemia

Singh, Prince — Thu, 26 Mar 2020 08:30:18 GMT-07:00

Unusual Cause for Continuous Renal Replacement Therapy Filter Clotting

Whitlow, Michael — Thu, 26 Mar 2020 08:30:18 GMT-07:00

Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

Zimmerman, Kurt A. — Mon, 02 Mar 2020 09:31:19 GMT-08:00

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: PRO

Eijgelsheim, Mark — Tue, 11 Feb 2020 01:38:00 GMT-08:00

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: CON

Gutgarts, Victoria — Tue, 11 Feb 2020 01:38:00 GMT-08:00

Profiling APOL1 Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics

Liu, Esther — Tue, 18 Feb 2020 02:10:57 GMT-08:00

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: Commentary

Perazella, Mark A. — Tue, 11 Feb 2020 01:38:00 GMT-08:00

Remote Treatment Monitoring on Hospitalization and Technique Failure Rates in Peritoneal Dialysis Patients

Chaudhuri, Sheetal — Mon, 17 Feb 2020 05:30:10 GMT-08:00

Seasonal and Secular Trends of Cardiovascular, Nutritional, and Inflammatory Markers in Patients on Hemodialysis

Terner, Zachary — Thu, 23 Jan 2020 10:23:26 GMT-08:00

Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease

Ayoola, Oluwagbemiga Oluwole — Fri, 31 Jan 2020 05:30:08 GMT-08:00

GFR Measurement and Chemotherapy Dosing in Patients with Kidney Disease and Cancer

McMahon, Blaithin A. — Mon, 13 Jan 2020 05:30:09 GMT-08:00

Chemotherapeutic agents require precise dosing to ensure optimal efficacy and minimize complications. For those agents that are removed from the body by the kidney, accurate knowledge of GFR is critical. In addition, GFR needs to be determined rapidly, easily, and, if possible, with little additional cost. The ability to easily measure GFR also allows for rapid detection of nephrotoxicity. Current methodologies include direct clearance measurement of an indicator substance or estimation of creatinine clearance or GFR through regression equations that use a serum marker, such as creatinine or cystatin C. These methodologies all have shortfalls and limitations, some of which are specific to the patient with cancer. Newer methodologies that directly measure GFR are in clinical trials and offer the ability to rapidly and noninvasively provide accurate estimates of drug clearance as well as detection of nephrotoxicity. These methods offer the opportunity to refine drug dosing and improve outcomes.

Hypertension and Acute Kidney Injury following an Allograft Biopsy

Zafar, Zubair Saeed — Thu, 27 Feb 2020 08:33:17 GMT-08:00

Prevalence and Persistence of Uremic Symptoms in Incident Dialysis Patients

Rhee, Eugene P. — Tue, 21 Jan 2020 07:11:18 GMT-08:00

Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

Gupta, Shruti — Tue, 14 Jan 2020 05:30:09 GMT-08:00

Immune checkpoint inhibitors (ICPIs) have transformed the landscape of oncology, but are associated with a variety of autoimmune adverse events, including AKI. ICPI-associated AKI (ICPI-AKI) is emerging as an increasingly frequent cause of AKI in patients with cancer, and poses unique diagnostic and management challenges to clinicians who care for these patients. In this review, we describe the incidence and risk factors for ICPI-AKI, including proton pump inhibitor use, CKD, and combination immunotherapy. We discuss the limitations of the various definitions used for ICPI-AKI in prior studies, and propose a novel classification system (definite, probable, and possible ICPI-AKI) that recognizes the diagnostic uncertainty inherent in many cases. We discuss the key clinicopathologic features and treatment strategies for ICPI-AKI, including the role of kidney biopsy versus empirical treatment with steroids. We also explore the under-studied area of ICPI use in the setting of solid organ transplantation, where nephrologists and oncologists must balance the risk of rejection versus treating the underlying malignancy. Finally, we summarize existing data on the role of ICPI rechallenge after an episode of ICPI-AKI.

Oxidized-ATP Attenuates Kidney Allograft Rejection By Inhibiting T-Cell, B-Cell, and Macrophage Activity

Ding, Xiang — Mon, 03 Feb 2020 05:30:09 GMT-08:00

Acute Bilateral Knee Pain in a Dialysis Patient with Severe Secondary Hyperparathyroidism

Allon, Michael — Thu, 27 Feb 2020 08:33:17 GMT-08:00

Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua

Ferguson, Ryan — Fri, 29 May 2020 08:26:18 GMT-07:00

Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty Acids

Wu, Huiling — Mon, 01 Jun 2020 02:02:41 GMT-07:00

Cell-Based Phenotypic Drug Screening Identifies Luteolin as Candidate Therapeutic for Nephropathic Cystinosis

De Leo, Ester — Fri, 05 Jun 2020 09:32:14 GMT-07:00

In Memorium: Burton Rose, 1942–2020

Hoenig, Melanie P. — Thu, 11 Jun 2020 07:13:30 GMT-07:00

Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in Mice

Silva Barbosa, Anne C. — Mon, 18 May 2020 01:11:01 GMT-07:00

Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring Problem

Farrington, Crystal A. — Mon, 18 May 2020 01:11:01 GMT-07:00

Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan

Akizawa, Tadao — Wed, 03 Jun 2020 06:22:57 GMT-07:00

Neutrophil Gelatinase–Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TH17 Immunity

Schreiber, Adrian — Tue, 02 Jun 2020 09:18:14 GMT-07:00

Authors' Reply

Macdougall, Iain C. — Mon, 01 Jun 2020 02:02:41 GMT-07:00

Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease

Bae, Kyongtae T. — Tue, 02 Jun 2020 09:18:11 GMT-07:00

Gerhard Giebisch (1927–2020): A Leader in Kidney Physiology

Murer, Heini — Fri, 05 Jun 2020 09:32:14 GMT-07:00

At the Crossroads for Intravenous Iron Dosing

Kshirsagar, Abhijit V. — Mon, 01 Jun 2020 02:02:41 GMT-07:00

Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric Glomerulosclerosis

Feng, Di — Mon, 15 Jun 2020 09:37:08 GMT-07:00

GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts

Eriksen, Bjørn O. — Thu, 04 Jun 2020 05:58:30 GMT-07:00

CKD Increases Carbonylation of HDL and Is Associated with Impaired Antiaggregant Properties

Florens, Nans — Tue, 09 Jun 2020 06:33:09 GMT-07:00

Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction

Bobot, Mickaël — Thu, 11 Jun 2020 07:13:30 GMT-07:00

This Month's Highlights

American Society of Nephrology — Tue, 30 Jun 2020 10:00:32 GMT-07:00

Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal Function

Hu, Chunyan — Tue, 02 Jun 2020 09:18:13 GMT-07:00

Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis

Gamboa, Jorge L. — Fri, 26 Jun 2020 07:25:19 GMT-07:00

Patient and Caregiver Perspectives on Terms Used to Describe Kidney Health

Tong, Allison — Thu, 25 Jun 2020 10:36:31 GMT-07:00

The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis

Peleg, Yonatan — Mon, 09 Mar 2020 06:34:41 GMT-07:00

The overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with “hard” endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.

The Feasibility and Safety of Obtaining Research Kidney Biopsy Cores in Patients with Diabetes

Hogan, Jonathan J. — Mon, 27 Apr 2020 08:36:27 GMT-07:00

Genetic Roadmap for Kidney Involvement of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Zhang, Yue-miao — Thu, 23 Apr 2020 06:00:39 GMT-07:00

EHR-Based Clinical Trials

Abdel-Kader, Khaled — Mon, 24 Feb 2020 09:10:56 GMT-08:00

Mineralocorticoid Receptor Antagonists in ESKD

Agarwal, Adhish — Wed, 08 Apr 2020 11:34:34 GMT-07:00

Complexities of Understanding Function from CKD-Associated DNA Variants

Lin, Jennie — Mon, 08 Jun 2020 05:28:45 GMT-07:00

Genome-wide association studies (GWASs) have facilitated the unbiased discovery of hundreds of genomic loci associated with CKD and kidney function. The vast majority of disease-associated DNA variants are noncoding. Those that are causal in CKD pathogenesis likely modulate transcription of target genes in a cell type–specific manner. To gain novel biological insights into mechanisms driving the development of CKD, the causal variants (which are usually not the most significant variant reported in a GWAS), their target genes, and causal cell types need to be identified. This functional validation requires a large number of new data sets, complex bioinformatics analyses, and experimental cellular and in vivo studies. Here, we review the basic principles and some of the current approaches being leveraged to assign functional significance to a genotype–phenotype association.

Nephrology Nomenclature: How to Accelerate Patient Anxiety, Suppress Engagement, and Mire the Advance of Medical Innovation

Conway, Paul T. — Thu, 25 Jun 2020 10:36:32 GMT-07:00

Understanding Work

Rosner, Mitchell Howard — Mon, 24 Feb 2020 09:10:56 GMT-08:00

Measuring Patient Activation as Part of Kidney Disease Policy: Are We There Yet?

Nair, Devika — Thu, 11 Jun 2020 07:13:31 GMT-07:00

Optimal care occurs when patients possess the skills, knowledge, and confidence needed to effectively manage their health. Promoting such patient activation in kidney disease care is increasingly being prioritized, and patient activation has recently emerged as central to kidney disease legislative policy in the United States. Two options of the Centers for Medicare and Medicaid Services Kidney Care Choices model—the Kidney Care First option and the Comprehensive Kidney Care Contracting option—now include patient activation as a quality metric; both models specifically name the patient activation measure (PAM) as the patient-reported outcome to use when assessing activation in kidney disease. Because nephrology practices participating in these models will receive capitated payments according to changes in patients’ PAM scores, it is time to more critically evaluate this measure as it applies to patients with kidney disease. In this review, we raise important issues related to the PAM’s applicability to kidney health, review and summarize existing literature that applies this measure to patients with kidney disease, and outline key elements to consider when implementing the PAM into practice and policy. Our aim is to spur further dialogue regarding how to assess and address patient activation in kidney disease to facilitate best practices for supporting patients in the successful management of their kidney health.

A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac Hypertrophy

Bao, Jing-Fu — Thu, 11 Jun 2020 07:13:31 GMT-07:00

Cardiac hypertrophy is a common feature in patients with CKD. Recent studies revealed that two phosphate regulators, fibroblast growth factor-23 and α-Klotho, are highly involved in the pathophysiologic process of CKD-induced cardiac hypertrophy. With decreasing renal function, elevated fibroblast growth factor-23 and decreased α-Klotho may contribute to cardiac hypertrophy by targeting the heart directly or by inducing systemic changes, such as vascular injury, hemodynamic disorders, and inflammation. However, several studies have demonstrated that disturbances in the fibroblast growth factor-23/α-Klotho axis do not lead to cardiac hypertrophy. In this review, we describe the cardiac effects of the fibroblast growth factor-23/α-Klotho axis and summarize recent progress in this field. In addition, we present not only the main controversies in this field but also provide possible directions to resolve these disputes.

Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in Korea

Cho, Jang-Hee — Mon, 01 Jun 2020 02:02:41 GMT-07:00

Presentation and Outcomes of Patients with ESKD and COVID-19

Valeri, Anthony M. — Thu, 28 May 2020 12:40:01 GMT-07:00

Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, China

Xiong, Fei — Fri, 08 May 2020 01:21:53 GMT-07:00

Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology

Batlle, Daniel — Mon, 04 May 2020 10:56:16 GMT-07:00

Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19

Adamsick, Meagan L. — Mon, 08 Jun 2020 05:30:27 GMT-07:00

Disaster Response to the COVID-19 Pandemic for Patients with Kidney Disease in New York City

Thu, 04 Jun 2020 05:58:30 GMT-07:00

Can Diet Induce Transplantation Tolerance?

Alegre, Maria-Luisa — Mon, 01 Jun 2020 02:02:41 GMT-07:00

Endogenous miR-204 Protects the Kidney against Chronic Injury in Hypertension and Diabetes

Cheng, Yuan — Tue, 02 Jun 2020 09:18:12 GMT-07:00

Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure

Nichols, Gregory A. — Tue, 02 Jun 2020 09:18:14 GMT-07:00

Mannose Binding Lectin Is Hydroxylated by Collagen Prolyl-4-hydroxylase and Inhibited by Some PHD Inhibitors

Bhute, Vijesh J. — Fri, 03 Apr 2020 01:25:57 GMT-07:00

US Trends in Prevalence of Sleep Problems and Associations with Chronic Kidney Disease and Mortality

Shieu, Monica — Fri, 01 May 2020 09:42:46 GMT-07:00

Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD

Gregg, L. Parker — Mon, 13 Apr 2020 07:38:45 GMT-07:00

Acute Abdominal Pain in a COVID-19 Patient

Mocerino, Ryan — Thu, 25 Jun 2020 05:30:20 GMT-07:00

Early Use of Telehealth in Home Dialysis during the COVID-19 Pandemic in New York City

Srivatana, Vesh — Tue, 28 Apr 2020 09:39:51 GMT-07:00

Automated Image Analyses of Glomerular Hypertrophy in a Mouse Model of Diabetic Nephropathy

Østergaard, Mette V. — Fri, 01 May 2020 09:42:46 GMT-07:00

Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective of Two Nephrologists in Brazil

Sesso, Ricardo — Wed, 29 Apr 2020 09:47:10 GMT-07:00

Providing Care to Patients with AKI and COVID-19 Infection: Experience of Front Line Nephrologists in New York

Fisher, Molly — Wed, 06 May 2020 01:43:10 GMT-07:00

Dialysis for Undocumented Immigrants: Challenges and Solutions

Berger, Joseph R. — Tue, 07 Apr 2020 01:33:52 GMT-07:00

The Role of Telemedicine in Providing Nephrology Care in Rural Hospitals

Lea, Janice P. — Wed, 22 Apr 2020 01:45:16 GMT-07:00

COVID-19 Perspective from a Hemodialysis Patient

Allon, Michael — Thu, 07 May 2020 01:26:35 GMT-07:00

Global Dialysis Perspective: Mexico

Vasquez-Jimenez, Enzo — Mon, 20 Apr 2020 08:06:50 GMT-07:00

Global Dialysis Perspective: Senegal

Niang, Abdou — Tue, 21 Apr 2020 01:45:16 GMT-07:00

The Advancing American Kidney Health (AAKH) Executive Order: Promise and Caveats for Expanding Access to Kidney Transplantation

Lentine, Krista L. — Wed, 22 Apr 2020 01:45:16 GMT-07:00

Setting Up and Expanding a Home Dialysis Program: Is There a Recipe for Success?

Ahmad, Masood — Fri, 01 May 2020 01:31:00 GMT-07:00

Home dialysis modalities remain significantly underused in the United States despite similar overall survival in the modalities, and recent incentives to expand these modalities. Although the absolute number of patients using home modalities has grown, the proportion compared to in-center hemodialysis (ICHD) continues to remain quite low. Well known barriers to home dialysis utilization exist, and an organized and team-based approach is required to overcome these barriers. Herein, we describe our efforts at growing our home dialysis program at a large academic medical center, with the proportion of home dialysis patients growing from 12% to 21% over the past 9 years. We prioritized individualized education for patients and better training for physicians, with the help of existing resources, aimed at better utilization of home modalities; an example includes dedicated dialysis education classes taught twice monthly by an experienced nurse practitioner, as well as the utilization of the dialysis educator from a dialysis provider for inpatient education of patients with CKD. The nephrology fellowship curriculum was restructured with emphasis on home modalities, and participation in annual home dialysis conferences has been encouraged. For timely placement and troubleshooting of access for dialysis, we followed a complementary team approach using surgeons and interventional radiologists and nephrologists, driven by a standardized protocol developed at UAB, and comanaged by our access coordinators. A team-based approach, with emphasis on staff engagement and leadership opportunities for dialysis nurses as well as collaborative efforts from a team of clinical nephrologists and the dialysis provider helped maintain efficiency, kindle growth, and provide consistently high-quality clinical care in the home program. Lastly, efforts at reducing burden of disease such as decreased number of monthly visits as well as using innovative strategies, such as telenephrology and assisted PD and HHD, were instrumental in reducing attrition.

ARHGEF7 (β-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function

Matsuda, Jun — Wed, 18 Mar 2020 10:07:58 GMT-07:00

The Value of Intravenous Iron: Beyond the Cave of Speculation

Coyne, Daniel W. — Mon, 06 Apr 2020 08:53:55 GMT-07:00

Tubular MST1/2 Deletion and Renal Fibrosis

Chang-Panesso, Monica — Mon, 06 Apr 2020 08:53:55 GMT-07:00

This Month's Highlights

American Society of Nephrology — Thu, 30 Apr 2020 10:00:29 GMT-07:00

Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis

Hollywood, Jennifer A. — Fri, 20 Mar 2020 07:40:36 GMT-07:00

Biomarkers of CKD in Children

Al-Aly, Ziyad — Tue, 31 Mar 2020 09:03:01 GMT-07:00

Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial

Jardine, Meg J. — Thu, 30 Apr 2020 10:00:30 GMT-07:00

Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis

Veys, Koenraad R.P. — Thu, 09 Apr 2020 04:52:44 GMT-07:00

Atorvastatin Reduces In Vivo Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula

Cui, Jie — Mon, 09 Mar 2020 06:36:01 GMT-07:00

SerpinB2 Regulates Immune Response in Kidney Injury and Aging

Sen, Payel — Tue, 24 Mar 2020 07:47:57 GMT-07:00

Tubule-Specific Mst1/2 Deficiency Induces CKD via YAP and Non-YAP Mechanisms

Xu, Chunhua — Mon, 06 Apr 2020 08:53:56 GMT-07:00

Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial

Macdougall, Iain C. — Mon, 06 Apr 2020 08:53:55 GMT-07:00

Erratum

American Society of Nephrology — Thu, 30 Apr 2020 10:00:30 GMT-07:00

Exocyst Genes Are Essential for Recycling Membrane Proteins and Maintaining Slit Diaphragm in Drosophila Nephrocytes

Wen, Pei — Wed, 01 Apr 2020 07:18:43 GMT-07:00

Plasma Biomarkers of Tubular Injury and Inflammation Are Associated with CKD Progression in Children

Greenberg, Jason H. — Tue, 31 Mar 2020 09:03:01 GMT-07:00

Tubular STAT3 Limits Renal Inflammation in Autosomal Dominant Polycystic Kidney Disease

Viau, Amandine — Wed, 01 Apr 2020 07:18:43 GMT-07:00

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation

Ellis, Robert J. — Wed, 01 Apr 2020 07:18:42 GMT-07:00

Interaction between Epithelial Sodium Channel γ-Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct

Sassi, Ali — Fri, 03 Apr 2020 06:03:27 GMT-07:00

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial

Marshall, Mark R. — Wed, 18 Mar 2020 10:07:58 GMT-07:00

Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis

Muzaale, Abimereki D. — Tue, 26 May 2020 02:18:37 GMT-07:00

Donor Age, Cold Ischemia Time, and Delayed Graft Function

Helanterä, Ilkka — Wed, 13 May 2020 07:48:48 GMT-07:00

Plasma Endothelin-1 and Risk of Death and Hospitalization in Patients Undergoing Maintenance Hemodialysis

Li, Ping — Thu, 07 May 2020 05:34:26 GMT-07:00

A Patient’s Perspective on Benzodiazepines, Co-Dispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis

Thomas, Cher — Tue, 26 May 2020 02:18:37 GMT-07:00

Donor Characteristics and Short-Term Kidney Allograft Outcomes

Friedewald, John J. — Wed, 13 May 2020 07:48:47 GMT-07:00

Can COMBINED Magnetic Resonance Imaging Measure the Progression of Kidney Disease?

Pruijm, Menno — Tue, 28 Apr 2020 06:21:15 GMT-07:00

Intradialytic Hypotension and Cardiac Arrhythmias in Patients Undergoing Maintenance Hemodialysis

Mc Causland, Finnian R. — Thu, 07 May 2020 05:34:27 GMT-07:00

Management of Active Surveillance-Eligible Prostate Cancer during Pretransplantation Workup of Patients with Kidney Failure: A Simulation Study

Bieri, Uwe — Thu, 07 May 2020 05:34:27 GMT-07:00

Environmental Risks to Kidney Health

Kaufman, James S. — Fri, 22 May 2020 05:48:44 GMT-07:00

Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical Practice

Garg, Amit X. — Fri, 10 Apr 2020 09:20:11 GMT-07:00

The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 “Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors” was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a “proof-of-concept” risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate’s profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.

The Effects of Intensive Blood Pressure Lowering on Markers of Mineral Metabolism in Persons with CKD in SPRINT

Ginsberg, Charles — Wed, 06 May 2020 04:57:17 GMT-07:00

Environment-Wide Association Study of CKD

Lee, Jeonghwan — Fri, 22 May 2020 09:48:27 GMT-07:00

Low Serum Bicarbonate and CKD Progression in Children

Brown, Denver D. — Thu, 28 May 2020 03:00:08 GMT-07:00

Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD

Srivastava, Anand — Tue, 28 Apr 2020 06:21:14 GMT-07:00

Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney Disorders

Molinari, Elisa — Thu, 05 Mar 2020 06:30:37 GMT-08:00

The class of human genetic kidney diseases is extremely broad and heterogeneous. Accordingly, the range of associated disease phenotypes is highly variable. Many children and adults affected by inherited kidney disease will progress to ESKD at some point in life. Extensive research has been performed on various different disease models to investigate the underlying causes of genetic kidney disease and to identify disease mechanisms that are amenable to therapy. We review some of the research highlights that, by modeling inherited kidney disease, contributed to a better understanding of the underlying pathomechanisms, leading to the identification of novel genetic causes, new therapeutic targets, and to the development of new treatments. We also discuss how the implementation of more efficient genome-editing techniques and tissue-culture methods for kidney research is providing us with personalized models for a precision-medicine approach that takes into account the specificities of the patient and the underlying disease. We focus on the most common model systems used in kidney research and discuss how, according to their specific features, they can differentially contribute to biomedical research. Unfortunately, no definitive treatment exists for most inherited kidney disorders, warranting further exploitation of the existing disease models, as well as the implementation of novel, complex, human patient–specific models to deliver research breakthroughs.

SONAR

Walsh, Michael — Tue, 04 Feb 2020 09:06:07 GMT-08:00

Impending Shortages of Kidney Replacement Therapy for COVID-19 Patients

Goldfarb, David S. — Tue, 28 Apr 2020 06:21:15 GMT-07:00

Screening for Cancer in Patients with Glomerular Diseases

Plaisier, Emmanuelle — Tue, 04 Feb 2020 09:06:07 GMT-08:00

How COVID-19 Has Changed the Management of Glomerular Diseases

Bomback, Andrew S. — Fri, 24 Apr 2020 04:43:33 GMT-07:00

Chronicle of a Death Foretold

Rifkin, Dena E. — Fri, 21 Feb 2020 07:05:01 GMT-08:00

Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant Evaluation

Murphy, Karly A. — Thu, 07 May 2020 05:34:26 GMT-07:00

Inequity in Access to Transplantation in the United Kingdom

Pruthi, Rishi — Thu, 28 May 2020 03:00:07 GMT-07:00

A Case of Nephrotic Syndrome after Allogeneic Stem Cell Transplantation

Hogan, Jonathan J. — Fri, 06 Mar 2020 07:58:10 GMT-08:00

Outpatient Management of the Kidney Transplant Recipient during the SARS-CoV-2 Virus Pandemic

Gleeson, Shana E. — Tue, 28 Apr 2020 06:21:15 GMT-07:00

Will Universal Access to Health Care Mean Equitable Access to Kidney Transplantation?

Harhay, Meera N. — Thu, 28 May 2020 03:00:08 GMT-07:00

ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment

Widmeier, Eugen — Thu, 07 May 2020 10:08:18 GMT-07:00

Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Ricardo, Ana C. — Thu, 16 Apr 2020 06:18:00 GMT-07:00

Quantitative Proteomics of All 14 Renal Tubule Segments in Rat

Limbutara, Kavee — Fri, 01 May 2020 07:53:50 GMT-07:00

Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids

Vangala, Chandan — Tue, 05 May 2020 05:45:03 GMT-07:00

Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney

Laszczyk, Ann M. — Thu, 07 May 2020 10:08:17 GMT-07:00

Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule

Wu, Peng — Wed, 15 Apr 2020 09:19:02 GMT-07:00

Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis

Mejia-Vilet, Juan M. — Thu, 16 Apr 2020 06:18:00 GMT-07:00

A Time-Updated, Parsimonious Model to Predict AKI in Hospitalized Children

Sandokji, Ibrahim — Thu, 07 May 2020 10:08:17 GMT-07:00

A Deregulated Stress Response Underlies Distinct INF2-Associated Disease Profiles

Bayraktar, Samet — Fri, 22 May 2020 05:50:33 GMT-07:00

Mitochondria Matter: A Critical Role of ADCK4 in Stabilizing the CoQ Complex in Podocytes in Steroid-Resistant Nephrotic Syndrome

Daehn, Ilse S. — Thu, 07 May 2020 10:08:19 GMT-07:00

Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease

Denburg, Michelle R. — Thu, 07 May 2020 10:08:18 GMT-07:00

Experimental Antiglomerular Basement Membrane GN Induced by a Peptide from Actinomyces

Gu, Qiu-hua — Fri, 22 May 2020 05:50:33 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 29 May 2020 09:59:49 GMT-07:00

Nephron-Specific Disruption of Polycystin-1 Induces Cyclooxygenase-2–Mediated Blood Pressure Reduction Independent of Cystogenesis

Lakshmipathi, Jayalakshmi — Thu, 16 Apr 2020 06:17:59 GMT-07:00

Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases

Jafree, Daniyal J. — Wed, 15 Apr 2020 09:19:01 GMT-07:00

The kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.

Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid–Mediated Activation of G Protein–Coupled Receptors GPR43 and GPR109A

Li, Yan Jun — Fri, 01 May 2020 07:53:51 GMT-07:00

The Immunocompromised Transplant Recipient and SARS-CoV-2 Infection

Fishman, Jay A. — Tue, 28 Apr 2020 02:53:06 GMT-07:00

Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia

Pei, Guangchang — Tue, 28 Apr 2020 02:53:06 GMT-07:00

Counterpoint: Twice-Weekly Hemodialysis Should Be an Approach of Last Resort Even in Times of Dialysis Unit Stress

Mehrotra, Rajnish — Thu, 16 Apr 2020 06:17:58 GMT-07:00

Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York

The Columbia University Kidney Transplant Program — Tue, 21 Apr 2020 04:45:09 GMT-07:00

COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

Willicombe, Michelle — Mon, 20 Apr 2020 12:06:55 GMT-07:00

On the Etymology of Nephritis: A Historical Appraisal of its Origins

Eknoyan, Garabed — Thu, 16 Apr 2020 06:18:00 GMT-07:00

Twice-Weekly Hemodialysis Is an Option for Many Patients in Times of Dialysis Unit Stress

Meyer, Timothy W. — Thu, 16 Apr 2020 06:17:58 GMT-07:00

The Broader Sharing of Deceased Donor Kidneys Is an Ethical and Legal Imperative

Klarman, Sharon E. — Mon, 20 Apr 2020 04:55:27 GMT-07:00

ESKD Treatment Choices Model: Responsible Home Dialysis Growth Requires Systems Changes

Wallace, Eric L. — Fri, 27 Mar 2020 11:05:26 GMT-07:00

Should Buttonhole Cannulation of Arteriovenous Fistulas be Used? PRO

Labriola, Laura — Tue, 14 Apr 2020 05:30:10 GMT-07:00

Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? Moderator Commentary

Agarwal, Anil K. — Tue, 14 Apr 2020 05:30:10 GMT-07:00

Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? CON

MacRae, Jennifer M. — Tue, 14 Apr 2020 05:30:10 GMT-07:00

Global Dialysis Perspective: Japan

Hanafusa, Norio — Thu, 16 Apr 2020 06:16:51 GMT-07:00

Peritoneal Dialysis for Acute Kidney Injury Treatment in the United States: Brought to You by the COVID-19 Pandemic

Srivatana, Vesh — Fri, 24 Apr 2020 02:30:46 GMT-07:00

Delivering Safe and Effective Hemodialysis in Patients with Suspected or Confirmed COVID-19 Infection: A Single-Center Perspective from Italy

Gallieni, Maurizio — Fri, 17 Apr 2020 10:39:57 GMT-07:00

α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

Fujimura, Rui — Tue, 24 Mar 2020 02:22:15 GMT-07:00

Serum Transaminases at Presentation and Association with Acute Dialysis in Children with Hemolytic Uremic Syndrome

Talathi, Saurabh — Thu, 19 Mar 2020 09:36:56 GMT-07:00

The Role of Telemedicine in Kidney Transplantation: Opportunities and Challenges

Concepcion, Beatrice P. — Fri, 03 Apr 2020 07:30:50 GMT-07:00

Providing Continuous Renal Replacement Therapy in Patients on Extracorporeal Membrane Oxygenation

Karakala, Nithin — Fri, 21 Feb 2020 07:05:02 GMT-08:00

Kidney Health Initiative Roadmap for Kidney Replacement Therapy

Gee, Patrick O. — Tue, 14 Apr 2020 10:16:18 GMT-07:00

Association of Serum Uromodulin with Death, Cardiovascular Events, and Kidney Failure in CKD

Steubl, Dominik — Tue, 14 Apr 2020 10:16:18 GMT-07:00

A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKD

Zager, Richard A. — Tue, 14 Apr 2020 10:16:18 GMT-07:00

Discontinuation of RAAS Inhibition in Children with Advanced CKD

van den Belt, Sophie M. — Mon, 06 Apr 2020 08:22:57 GMT-07:00

A Primer on Congenital Anomalies of the Kidneys and Urinary Tracts (CAKUT)

Murugapoopathy, Vasikar — Wed, 18 Mar 2020 08:55:09 GMT-07:00

Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.

Systems Biology and Kidney Disease

Schaub, Jennifer A. — Tue, 28 Jan 2020 11:10:19 GMT-08:00

The kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.

Metabolic Disorders with Kidney Transplant

Cohen, Elizabeth — Mon, 13 Apr 2020 10:57:30 GMT-07:00

Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient’s ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%–30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.

On the Frontline of the COVID-19 Outbreak

Watnick, Suzanne — Sat, 28 Mar 2020 07:24:34 GMT-07:00

Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19

Sparks, Matthew A. — Fri, 27 Mar 2020 02:03:21 GMT-07:00

Lessons from the Experience in Wuhan to Reduce Risk of COVID-19 Infection in Patients Undergoing Long-Term Hemodialysis

Li, Junhua — Thu, 02 Apr 2020 01:32:19 GMT-07:00

COVID-19 and the Inpatient Dialysis Unit

Burgner, Anna — Fri, 03 Apr 2020 02:54:11 GMT-07:00

Mitigating Risk of COVID-19 in Dialysis Facilities

Kliger, Alan S. — Fri, 20 Mar 2020 01:20:05 GMT-07:00

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial

Hayashi, Terumasa — Fri, 03 Apr 2020 06:00:08 GMT-07:00

Fructose Production and Metabolism in the Kidney

Nakagawa, Takahiko — Mon, 06 Apr 2020 08:53:56 GMT-07:00

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.

Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors

Packer, Milton — Fri, 10 Apr 2020 07:16:41 GMT-07:00

Growing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation—sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)—can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized by marked suppression of SIRT1 and AMPK, leading to a diminution in autophagic flux in glomerular podocytes and renal tubules and markedly increasing their susceptibility to renal injury. Importantly, because insulin acts to depress autophagic flux, these derangements in nutrient deprivation signaling are not ameliorated by antihyperglycemic drugs that enhance insulin secretion or signaling. Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting. In contrast, the effects of sodium-glucose cotransporter–2 (SGLT2) inhibitors may be related primarily to enhanced SIRT1 and HIF-2α signaling; this can explain the effects of SGLT2 inhibitors to promote ketonemia and erythrocytosis and potentially underlies their actions to increase autophagy and mute inflammation in the diabetic kidney. These distinctions may contribute importantly to the consistent benefit of SGLT2 inhibitors to slow the deterioration in glomerular function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes.

Protein Kinase C-δ Mediates Kidney Tubular Injury in Cold Storage–Associated Kidney Transplantation

Zhu, Jiefu — Tue, 14 Apr 2020 10:16:32 GMT-07:00

In Vivo Assessment of Size-Selective Glomerular Sieving in Transplanted Human Induced Pluripotent Stem Cell–Derived Kidney Organoids

van den Berg, Cathelijne W. — Thu, 30 Apr 2020 10:00:29 GMT-07:00

Housing Insecurity and Risk of Adverse Kidney Outcomes

Novick, Tessa K. — Tue, 31 Mar 2020 06:00:11 GMT-07:00

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

Leehey, David J. — Fri, 28 Feb 2020 05:30:09 GMT-08:00

Diabetic kidney disease (DKD) is the most common cause of ESKD in the United States and worldwide. Current treatment for DKD includes strict glycemic control and normalization of BP with renin-angiotensin-aldosterone system (RAAS) blockade. Although RAAS blockers slow progression of disease, they do not generally prevent ESKD and none of the studies with these agents in DKD included patients who were nonproteinuric, which make up an increasingly large percentage of patients with diabetes now seen in clinical practice. Recent studies with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown beneficial renal effects, and the benefits of SGLT2 inhibitors likely extend to patients who are nonproteinuric. However, there remains a need to develop new therapies for DKD, particularly in those patients with advanced disease. A role of chronic low-grade inflammation in microvascular complications in patients with diabetes has now been widely accepted. Large clinical trials are being carried out with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress. The Food and Drug Administration–approved, nonspecific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-inflammatory effects in both animal and human studies by inhibiting the production of proinflammatory cytokines. Small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD, raising the possibility that a clinically available drug may be able to be repurposed to treat this disease. A large, multicenter, randomized clinical trial to determine whether this agent can decrease time to ESKD or death is currently being conducted, but results will not be available for several years. At this time, the combination of RAAS blockade plus SGLT2 inhibition is considered standard of care for DKD, but it may be reasonable for clinicians to consider addition of PTX in patients whose disease continues to progress despite optimization of current standard-of-care therapies.

Fluid Overload and Mortality in Patients with Severe Acute Kidney Injury and Extracorporeal Membrane Oxygenation

Gunning, Samantha — Wed, 25 Mar 2020 12:39:00 GMT-07:00

Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective of Two Nephrologists in the United States

Mokrzycki, Michele H. — Wed, 25 Mar 2020 12:38:59 GMT-07:00

Raising the Volume on Alport Syndrome: A Patient Perspective

Dunleavy, Megan E. — Thu, 12 Mar 2020 09:15:10 GMT-07:00

Clinical Applications of Genetic Discoveries in Kidney Transplantation: a Review

Marin, Ethan P. — Wed, 11 Mar 2020 01:47:44 GMT-07:00

Growth in knowledge of the genetics of kidney disease has revealed that significant percentages of patients with diverse types of nephropathy have causative mutations. Genetic testing is poised to play an increasing role in the care of patients with kidney disease. The role of genetic testing in kidney transplantation is not well established. This review will explore the ways in which genetic testing may be applied to improve the care of kidney transplant recipients and donors.

Buttonhole Cannulation of Arteriovenous Fistulas in the United States

Vachharajani, Tushar J. — Fri, 06 Mar 2020 05:29:38 GMT-08:00

The cannulation technique of a hemodialysis vascular access has remained controversial with differing viewpoints. The quality of dialysis, overall patient safety, and individual dialysis experience often dictate the type of cannulation technique used in clinical practice. The three commonly used techniques to access a hemodialysis vascular access are the rope ladder, area, and buttonhole. Although the buttonhole technique has been around since the mid-1970s, the dialysis community remains divided on its suitability for routine use to provide maintenance hemodialysis therapy. The proponents of this technique value the ease of cannulation with less pain and discomfort whereas the opponents highlight the increased risk of infection. The actual clinical evidence from the United States is limited and remains inconclusive. The current review provides an overview of the available experience from the United States, highlighting the correct technique of creating a buttonhole, summarizing the current evidence, and recommending a need for larger randomized controlled studies in both in-center and home hemodialysis populations.

Buttonhole Cannulation of Arteriovenous Fistulas: a Dialysis Nurse’s Perspective

Bushey, Margaret — Thu, 05 Mar 2020 10:06:45 GMT-08:00

Sucroferric Oxyhydroxide as Part of Combination Phosphate Binder Therapy among Hemodialysis Patients

Molony, Donald A. — Mon, 23 Mar 2020 01:15:34 GMT-07:00

The Changing Landscape of Fabry Disease

Svarstad, Einar — Wed, 04 Mar 2020 07:23:06 GMT-08:00

Intravascular Volume Assessment in the Critically Ill Patient

Vincent, Jean-Louis — Tue, 03 Dec 2019 05:22:08 GMT-08:00

Association of 24-Hour Ambulatory Blood Pressure Patterns with Cognitive Function and Physical Functioning in CKD

Ghazi, Lama — Thu, 26 Mar 2020 05:59:15 GMT-07:00

Safety of Liraglutide in Type 2 Diabetes and Chronic Kidney Disease

Mann, Johannes F.E. — Wed, 04 Mar 2020 07:23:06 GMT-08:00

Liraglutide for the Treatment of Type 2 Diabetes and Safety in Diabetic Kidney Disease

Cherney, David Z. — Wed, 04 Mar 2020 07:23:05 GMT-08:00

Single Cell Sequencing and Kidney Organoids Generated from Pluripotent Stem Cells

Wu, Haojia — Tue, 28 Jan 2020 11:10:20 GMT-08:00

Methods to differentiate human pluripotent stem cells into kidney organoids were first introduced about 5 years ago, and since that time, the field has grown substantially. Protocols are producing increasingly complex three-dimensional structures, have been used to model human kidney disease, and have been adapted for high-throughput screening. Over this same time frame, technologies for massively parallel, single-cell RNA sequencing (scRNA-seq) have matured. Now, both of these powerful approaches are being combined to better understand how kidney organoids can be applied to the understanding of kidney development and disease. There are several reasons why this is a synergistic combination. Kidney organoids are complicated and contain many different cell types of variable maturity. scRNA-seq is an unbiased technology that can comprehensively categorize cell types, making it ideally suited to catalog all cell types present in organoids. These same characteristics also make scRNA-seq a powerful approach for quantitative comparisons between protocols, batches, and pluripotent cell lines as it becomes clear that reproducibility and quality can vary across all three variables. Lineage trajectories can be reconstructed using scRNA-seq data, enabling the rational adjustment of differentiation strategies to promote maturation of desired kidney cell types or inhibit differentiation of undesired off-target cell types. Here, we review the ways that scRNA-seq has been successfully applied in the organoid field and predict future applications for this powerful technique. We also review other developing single-cell technologies and discuss how they may be combined, using “multiomic” approaches, to improve our understanding of kidney organoid differentiation and usefulness in modeling development, disease, and toxicity testing.

Consenting for Dialysis or Its Alternative

Li, Kelly Chenlei — Tue, 04 Feb 2020 09:06:06 GMT-08:00

Making Assisted Peritoneal Dialysis a Reality in the United States

Oliver, Matthew J. — Wed, 18 Dec 2019 08:16:50 GMT-08:00

Contraception and CKD

Burgner, Anna — Mon, 18 Nov 2019 08:35:30 GMT-08:00

The Long Road to Kidney Transplantation

Purnell, Tanjala S. — Tue, 24 Mar 2020 07:47:32 GMT-07:00

Distance from a Transplant Center and Getting Listed for a Transplant

Garner, Lisa — Tue, 24 Mar 2020 07:47:33 GMT-07:00

Distance to Kidney Transplant Center and Access to Early Steps in the Kidney Transplantation Process in the Southeastern United States

McPherson, Laura J. — Tue, 24 Mar 2020 07:47:33 GMT-07:00

This Month's Highlights

American Society of Nephrology — Tue, 31 Mar 2020 10:00:23 GMT-07:00

MoCA: Turn Your Mind to It

Jassal, Sarbjit V. — Wed, 04 Mar 2020 07:26:28 GMT-08:00

Erratum

American Society of Nephrology — Tue, 31 Mar 2020 10:00:23 GMT-07:00

Evaluation of Screening Tests for Cognitive Impairment in Patients Receiving Maintenance Hemodialysis

Drew, David A. — Wed, 04 Mar 2020 07:26:27 GMT-08:00

Challenges in Understanding Acute Postinfectious Glomerulonephritis: Are Anti-Factor B Autoantibodies the Answer?

Noris, Marina — Fri, 06 Mar 2020 07:59:08 GMT-08:00

Coaxing Anti-Inflammatory Granulocytes to Prevent Ischemic Kidney Injury: A Fine Balance

Salama, Alan D. — Wed, 04 Mar 2020 07:26:27 GMT-08:00

Pulling the Hood off Genetic Susceptibility to Hypertensive Renal Disease

Dhande, Isha S. — Mon, 02 Mar 2020 08:36:54 GMT-08:00

Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss

Najafian, Behzad — Tue, 03 Mar 2020 08:49:07 GMT-08:00

Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes

Royal, Virginie — Fri, 21 Feb 2020 07:08:51 GMT-08:00

Two Mineralocorticoid Receptor–Mediated Mechanisms of Pendrin Activation in Distal Nephrons

Ayuzawa, Nobuhiro — Fri, 07 Feb 2020 09:57:49 GMT-08:00

Kidney Clearance of Secretory Solutes Is Associated with Progression of CKD: The CRIC Study

Chen, Yan — Mon, 23 Mar 2020 05:30:19 GMT-07:00

α2A-Adrenoceptors Modulate Renal Sympathetic Neurotransmission and Protect against Hypertensive Kidney Disease

Hering, Lydia — Fri, 21 Feb 2020 07:08:52 GMT-08:00

A Mutation in γ-Adducin Impairs Autoregulation of Renal Blood Flow and Promotes the Development of Kidney Disease

Fan, Fan — Thu, 06 Feb 2020 05:10:45 GMT-08:00

Renoprotective and Immunomodulatory Effects of GDF15 following AKI Invoked by Ischemia-Reperfusion Injury

Liu, Jing — Fri, 07 Feb 2020 09:57:49 GMT-08:00

Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppressor Cells

Yan, Ji-Jing — Wed, 04 Mar 2020 07:26:27 GMT-08:00

Anti-Factor B Antibodies and Acute Postinfectious GN in Children

Chauvet, Sophie — Fri, 07 Feb 2020 09:57:50 GMT-08:00

Cellular and Molecular Mechanisms of Kidney Injury in 2,8-Dihydroxyadenine Nephropathy

Klinkhammer, Barbara Mara — Fri, 21 Feb 2020 07:08:53 GMT-08:00

The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Johnsen, Marc — Fri, 28 Feb 2020 07:34:46 GMT-08:00

Dnmt3a and Dnmt3b-Decommissioned Fetal Enhancers are Linked to Kidney Disease

Guan, Yuting — Tue, 03 Mar 2020 08:49:07 GMT-08:00

Burnout and Emotional Well-Being among Nephrology Fellows: A National Online Survey

Agrawal, Varun — Mon, 02 Mar 2020 08:36:54 GMT-08:00

Terminally Differentiated Effector Memory CD8+ T Cells Identify Kidney Transplant Recipients at High Risk of Graft Failure

Jacquemont, Lola — Thu, 12 Mar 2020 07:59:16 GMT-07:00

Racial and Ethnic Disparities in Pregnancy-Related Acute Kidney Injury

Beers, Kelly — Wed, 12 Feb 2020 01:34:15 GMT-08:00

“It’s Hard, but I’m Grateful for It”: A Patient Perspective on Hemodialysis

Allon, Michael — Thu, 26 Mar 2020 08:30:18 GMT-07:00

From Recurrence to Recovery: A Transplant Patient’s Perspective

Fontanella, Antonio — Thu, 13 Feb 2020 01:47:01 GMT-08:00

Glomerular Diseases in Patients with Diabetes Mellitus: An Underappreciated Epidemic

Freeman, Natasha S. — Thu, 06 Feb 2020 10:35:00 GMT-08:00

Global Dialysis Perspective: Brazil

Sesso, Ricardo — Tue, 04 Feb 2020 01:26:18 GMT-08:00

The Impact of Household Income on Kidney Care

Weed, Stephen — Thu, 20 Feb 2020 07:32:16 GMT-08:00

Socioeconomic Position and Incidence of Glomerular Diseases

Canney, Mark — Thu, 20 Feb 2020 07:32:16 GMT-08:00

Association of APOL1 Risk Genotype and Air Pollution for Kidney Disease

Paranjpe, Ishan — Thu, 20 Feb 2020 07:32:16 GMT-08:00

Air Pollution and Kidney Disease

Al-Aly, Ziyad — Thu, 27 Feb 2020 12:17:32 GMT-08:00

Social Determinants of Glomerular Disease

O'Shaughnessy, Michelle M. — Thu, 20 Feb 2020 07:32:16 GMT-08:00

Evaluation and Treatment of Acute Rejection in Kidney Allografts

Cooper, James E. — Mon, 17 Feb 2020 05:12:58 GMT-08:00

Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should remain high on any differential diagnosis of unexplained graft dysfunction because of the potential negative effect on graft longevity. Understanding the pre- and post-transplant risk factors for acute rejection can help estimate the probability of immunologic graft damage, and accurate identification of the type and severity of acute rejection will guide appropriate treatment. Tissue biopsy remains the gold standard for evaluating immunologic graft damage, and the histologic definition of acute rejection has evolved in recent years. Intravenous steroids and T cell depletion remain the standard therapy for T cell–mediated rejection and are effective in reversing most cases. Plasma exchange and intravenous Ig, with or without rituximab, are most commonly used for the treatment of antibody-mediated rejection and several newer agents have recently been investigated for severe cases. This review aims to provide the general nephrologist caring for transplant recipients with an approach to immunologic risk assessment and a summary of recent advances in the diagnosis and treatment of acute graft rejection.

Long-Term Outcomes in Patients with Acute Kidney Injury

Noble, Rebecca A. — Wed, 19 Feb 2020 08:33:16 GMT-08:00

The long-term sequelae of AKI have received increasing attention so that its associations with a number of adverse outcomes, including higher mortality and development of CKD, are now widely appreciated. These associations take on particular importance when considering the high incidence of AKI, with a lack of proven interventions and uncertainties around optimal care provision meaning that the long-term sequelae of AKI present a major unmet clinical need. In this review, we examine the published data that inform our current understanding of long-term outcomes following AKI and discuss potential knowledge gaps, covering long-term mortality, CKD, progression to ESKD, proteinuria, cardiovascular events, recurrent AKI, and hospital readmission.

Life Course Socioeconomic Status, Allostatic Load, and Kidney Health in Black Americans

Lunyera, Joseph — Wed, 19 Feb 2020 08:33:17 GMT-08:00

Particulate Matter and Albuminuria, Glomerular Filtration Rate, and Incident CKD

Blum, Matthew F. — Thu, 27 Feb 2020 12:17:32 GMT-08:00

A Coaching Program to Improve Dietary Intake of Patients with CKD

Kelly, Jaimon T. — Fri, 28 Feb 2020 06:27:30 GMT-08:00

Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline in SPRINT Trial Participants with CKD

Malhotra, Rakesh — Fri, 28 Feb 2020 06:27:29 GMT-08:00

Sex and Glomerular Filtration Rate Trajectories in Children

Bonnéric, Stéphanie — Fri, 28 Feb 2020 06:27:29 GMT-08:00

Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol in Patients Receiving Maintenance Hemodialysis

Thadhani, Ravi I. — Fri, 28 Feb 2020 06:27:30 GMT-08:00

Proteomics and Metabolomics in Kidney Disease, including Insights into Etiology, Treatment, and Prevention

Dubin, Ruth F. — Mon, 21 Oct 2019 07:55:53 GMT-07:00

In this review of the application of proteomics and metabolomics to kidney disease research, we review key concepts, highlight illustrative examples, and outline future directions. The proteome and metabolome reflect the influence of environmental exposures in addition to genetic coding. Circulating levels of proteins and metabolites are dynamic and modifiable, and thus amenable to therapeutic targeting. Design and analytic considerations in proteomics and metabolomics studies should be tailored to the investigator’s goals. For the identification of clinical biomarkers, adjustment for all potential confounding variables, particularly GFR, and strict significance thresholds are warranted. However, this approach has the potential to obscure biologic signals and can be overly conservative given the high degree of intercorrelation within the proteome and metabolome. Mass spectrometry, often coupled to up-front chromatographic separation techniques, is a major workhorse in both proteomics and metabolomics. High-throughput antibody- and aptamer-based proteomic platforms have emerged as additional, powerful approaches to assay the proteome. As the breadth of coverage for these methodologies continues to expand, machine learning tools and pathway analyses can help select the molecules of greatest interest and categorize them in distinct biologic themes. Studies to date have already made a substantial effect, for example elucidating target antigens in membranous nephropathy, identifying a signature of urinary peptides that adds prognostic information to urinary albumin in CKD, implicating circulating inflammatory proteins as potential mediators of diabetic nephropathy, demonstrating the key role of the microbiome in the uremic milieu, and highlighting kidney bioenergetics as a modifiable factor in AKI. Additional studies are required to replicate and expand on these findings in independent cohorts. Further, more work is needed to understand the longitudinal trajectory of select protein and metabolite markers, perform transomics analyses within merged datasets, and incorporate more kidney tissue–based investigation.

Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease

Tan, Kathryn C.B. — Wed, 19 Feb 2020 08:33:16 GMT-08:00

Personalizing Donor Kidney Selection

Foley, David P. — Tue, 17 Dec 2019 08:31:59 GMT-08:00

Management of Membranous Nephropathy after MENTOR

Trivin-Avillach, Claire — Mon, 18 Nov 2019 08:35:30 GMT-08:00

How the Kidney Health Initiative Catalyzes Innovation in a Dynamic Environment

Harris, Raymond C. — Fri, 06 Dec 2019 07:58:57 GMT-08:00

Survival after Kidney Transplantation during Childhood and Adolescence

Francis, Anna — Wed, 19 Feb 2020 08:33:17 GMT-08:00

Secular Trends in Survival Outcomes of Kidney Transplantation for Children

Amaral, Sandra — Wed, 19 Feb 2020 08:33:17 GMT-08:00

Electrolyte Disorders in Kidney Transplantation

Miles, Clifford D. — Mon, 17 Feb 2020 05:12:59 GMT-08:00

A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease

Bovée, Dominique M. — Wed, 29 Jan 2020 07:29:00 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 28 Feb 2020 10:00:27 GMT-08:00

Measuring Quality in Kidney Care: An Evaluation of Existing Quality Metrics and Approach to Facilitating Improvements in Care Delivery

Mendu, Mallika L. — Thu, 13 Feb 2020 11:00:13 GMT-08:00

A Randomized Trial of Empagliflozin to Increase Plasma Sodium Levels in Patients with the Syndrome of Inappropriate Antidiuresis

Refardt, Julie — Tue, 04 Feb 2020 09:07:32 GMT-08:00

Racial and Sex Disparities in Catheter Use and Dialysis Access in the United States Medicare Population

Arya, Shipra — Wed, 15 Jan 2020 06:42:02 GMT-08:00

Racial/Ethnic Disparities in Atrial Fibrillation Treatment and Outcomes among Dialysis Patients in the United States

Waddy, Salina P. — Thu, 20 Feb 2020 07:33:36 GMT-08:00

Aldosterone Regulates Pendrin and Epithelial Sodium Channel Activity through Intercalated Cell Mineralocorticoid Receptor–Dependent and –Independent Mechanisms over a Wide Range in Serum Potassium

Pham, Truyen D. — Thu, 13 Feb 2020 11:00:12 GMT-08:00

Inhibition of Endothelial PHD2 Suppresses Post-Ischemic Kidney Inflammation through Hypoxia-Inducible Factor-1

Rajendran, Ganeshkumar — Wed, 29 Jan 2020 07:29:00 GMT-08:00

Injured Podocytes Are Sensitized to Angiotensin II–Induced Calcium Signaling

Binz-Lotter, Julia — Fri, 10 Jan 2020 07:34:23 GMT-08:00

Bundled Payment Reform and Dialysis Facility Closures in ESKD

Norouzi, Sayna — Tue, 04 Feb 2020 09:07:33 GMT-08:00

Estimating Urine Albumin-to-Creatinine Ratio from Protein-to-Creatinine Ratio: Development of Equations using Same-Day Measurements

Weaver, Robert G. — Wed, 05 Feb 2020 07:27:32 GMT-08:00

How Does Aldosterone Work in the β-Intercalated Cell?

Leipziger, Jens — Thu, 13 Feb 2020 11:00:11 GMT-08:00

Aligning Albuminuria and Proteinuria Measurements

Coresh, Josef — Wed, 05 Feb 2020 07:27:32 GMT-08:00

Measuring Up

Palevsky, Paul M. — Thu, 13 Feb 2020 11:00:12 GMT-08:00

Erratum

American Society of Nephrology — Fri, 28 Feb 2020 10:00:27 GMT-08:00

Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease

Wesson, Donald E. — Mon, 27 Jan 2020 06:13:17 GMT-08:00

Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.

Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis

Koehler, Sybille — Tue, 11 Feb 2020 01:15:14 GMT-08:00

Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment

Batchelor, Elizabeth Katherine — Mon, 10 Feb 2020 08:18:57 GMT-08:00

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Hypothesis as to How a Common Missense Mutation in COL4A3 May Confer Protection against Diabetic Kidney Disease

Pieri, Myrtani — Mon, 27 Jan 2020 06:13:17 GMT-08:00

Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice

Sugahara, Mai — Wed, 29 Jan 2020 07:28:59 GMT-08:00

Transplantation-Induced Ischemia-Reperfusion Injury Modulates Antigen Presentation by Donor Renal CD11c+F4/80+ Macrophages through IL-1R8 Regulation

Aiello, Sistiana — Mon, 27 Jan 2020 06:13:17 GMT-08:00

Global Dialysis Perspective: Canada

Blake, Peter G. — Thu, 16 Jan 2020 05:30:10 GMT-08:00

Should My Patient Accept a Kidney from a Hepatitis C Virus–Infected Donor?

Pagan, Javier — Wed, 15 Jan 2020 05:30:09 GMT-08:00

Global Dialysis Perspective: Israel

Haviv, Yosef S. — Mon, 20 Jan 2020 07:20:02 GMT-08:00

Safety of Gadolinium-Based Contrast Agents in Patients with Stage 4 and 5 Chronic Kidney Disease: a Radiologist’s Perspective

Soloff, Erik V. — Thu, 27 Feb 2020 08:33:17 GMT-08:00

Trends in the Proportions of Women Program Chairs, Moderators, and Speakers at American Society of Nephrology Kidney Week 2011–2019

Malieckal, Deepa A. — Thu, 23 Jan 2020 07:59:44 GMT-08:00

Patient and Kidney Allograft Survival with National Kidney Paired Donation

Leeser, David B. — Tue, 28 Jan 2020 11:10:19 GMT-08:00

Socioeconomic Determinants of Quality of Life in Patients with Kidney Diseases

Jhamb, Manisha — Thu, 30 Jan 2020 01:02:25 GMT-08:00

Patient Perspective on CKD in India

Uppaluri, Rama Krishna Rao — Thu, 30 Jan 2020 01:02:25 GMT-08:00

Nonmedical Factors and Health-Related Quality of Life in CKD in India

Modi, Gopesh K. — Thu, 30 Jan 2020 01:02:26 GMT-08:00

Association of Sleep Apnea with Mortality in Patients with Advanced Kidney Disease

Jhamb, Manisha — Wed, 22 Jan 2020 07:48:33 GMT-08:00

Screening for CKD To Improve Processes of Care among Nondiabetic Veterans with Hypertension

Peralta, Carmen A. — Fri, 07 Feb 2020 10:00:21 GMT-08:00

Introduction to Genomics of Kidney Disease

Sampson, Matthew G. — Tue, 28 Jan 2020 11:10:18 GMT-08:00

The Genetic Architecture of Kidney Disease

Pollak, Martin R. — Tue, 28 Jan 2020 11:10:19 GMT-08:00

The kidney is subject to a wide range of abnormalities, many of which have a significant hereditable component. Next generation sequencing is increasingly bringing the genetic drivers of Mendelian disease into focus at the base pair level, whereas inexpensive genotyping arrays have surveyed hundreds of thousands of individuals to identify common variants that predispose to kidney dysfunction. In this first article in a CJASN series on kidney genomics, we review how both rare and common variants contribute to kidney disease, explore how evolution may influence the genetic variants that affect kidney function, consider how genetic information is and will be used in the clinic, and identify some of the most important future directions for kidney disease research. Forthcoming articles in the series will elaborate on many of these themes.

Sodium Bicarbonate Supplementation and Urinary TGF-β1 in Nonacidotic Diabetic Kidney Disease

Raphael, Kalani L. — Thu, 23 Jan 2020 07:59:43 GMT-08:00

Therapeutic Relowering of Plasma Sodium after Overly Rapid Correction of Hyponatremia

Rondon-Berrios, Helbert — Thu, 10 Oct 2019 04:05:04 GMT-07:00

Sodium Glucose Cotransporter 2 Inhibition Heralds a Call-to-Action for Diabetic Kidney Disease

Tuttle, Katherine R. — Mon, 18 Nov 2019 08:35:30 GMT-08:00

Peritoneal Dialysis in the Obese Patient

Kennedy, Claire — Mon, 18 Nov 2019 08:35:30 GMT-08:00

Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients

Gomes-Neto, António W. — Thu, 02 Jan 2020 05:50:18 GMT-08:00

Acute Kidney Injury and CKD Associated with Hematopoietic Stem Cell Transplantation

Renaghan, Amanda DeMauro — Fri, 13 Dec 2019 07:20:38 GMT-08:00

Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%–73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy.

Facing the Vexing Problem of Recurrent FSGS after Kidney Transplantation

Lafayette, Richard A. — Thu, 23 Jan 2020 07:59:43 GMT-08:00

Recurrence of FSGS after Kidney Transplantation in Adults

Uffing, Audrey — Thu, 23 Jan 2020 07:59:44 GMT-08:00

Personalizing the Kidney Transplant Decision

Sawinski, Deirdre — Tue, 01 Oct 2019 10:02:18 GMT-07:00

Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study

Olaniran, Kabir O. — Fri, 06 Dec 2019 08:00:11 GMT-08:00

FSGS-Causing INF2 Mutation Impairs Cleaved INF2 N-Fragment Functions in Podocytes

Subramanian, Balajikarthick — Fri, 10 Jan 2020 07:34:23 GMT-08:00

Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers

Mishima, Eikan — Mon, 25 Nov 2019 06:07:27 GMT-08:00

Unraveling the Complexity of the Renal Mononuclear Phagocyte System by Genetic Cell Lineage Tracing

Böhner, Alexander M.C. — Mon, 13 Jan 2020 08:46:56 GMT-08:00

The Kidney Contains Ontogenetically Distinct Dendritic Cell and Macrophage Subtypes throughout Development That Differ in Their Inflammatory Properties

Salei, Natallia — Mon, 13 Jan 2020 08:46:56 GMT-08:00

Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy

Levine, Adam P. — Thu, 09 Jan 2020 10:35:16 GMT-08:00

BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats

Bidani, Anil K. — Mon, 02 Dec 2019 08:42:19 GMT-08:00

Incident Hospitalization with Major Cardiovascular Diseases and Subsequent Risk of ESKD: Implications for Cardiorenal Syndrome

Ishigami, Junichi — Thu, 09 Jan 2020 10:35:15 GMT-08:00

Therapeutic Myeloperoxidase Inhibition Attenuates Neutrophil Activation, ANCA-Mediated Endothelial Damage, and Crescentic GN

Antonelou, Marilina — Thu, 26 Dec 2019 09:27:02 GMT-08:00

Clinical Features and Outcomes of Immune Checkpoint Inhibitor–Associated AKI: A Multicenter Study

Cortazar, Frank B. — Thu, 02 Jan 2020 05:51:25 GMT-08:00

Loss of Histone H3 K79 Methyltransferase Dot1l Facilitates Kidney Fibrosis by Upregulating Endothelin 1 through Histone Deacetylase 2

Zhang, Long — Mon, 16 Dec 2019 08:27:50 GMT-08:00

Kinin B1 Receptor Is Important in the Pathogenesis of Myeloperoxidase-Specific ANCA GN

Hu, Peiqi — Tue, 26 Nov 2019 07:04:59 GMT-08:00

Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

Issa, Naim — Thu, 23 Jan 2020 08:00:17 GMT-08:00

The Dialysis Safety Net: Who Cares for Those Without Medicare?

Thorsness, Rebecca — Fri, 24 Jan 2020 07:49:53 GMT-08:00

Renal Functional Decline in Sickle Cell Disease and Trait

Nath, Karl A. — Fri, 24 Jan 2020 07:49:54 GMT-08:00

New Paradigm for Cytoskeletal Organization in Podocytes: Proteolytic Fragments of INF2 Formin Function Independently of INF2 Actin Regulatory Activity

Krendel, Mira — Fri, 10 Jan 2020 07:34:23 GMT-08:00

Authors' Reply

Rule, Andrew D. — Mon, 23 Dec 2019 09:37:08 GMT-08:00

Current CKD Definition Takes into Account Both Relative and Absolute Risk

Coresh, Josef — Mon, 23 Dec 2019 09:37:08 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 31 Jan 2020 10:00:30 GMT-08:00

Age-Dependent Definition of CKD

Trachtman, Howard — Mon, 23 Dec 2019 09:37:08 GMT-08:00

Safety-Net Care for Maintenance Dialysis in the United States

Erickson, Kevin F. — Thu, 19 Dec 2019 06:49:04 GMT-08:00

CFHR Gene Variations Provide Insights in the Pathogenesis of the Kidney Diseases Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

Zipfel, Peter F. — Fri, 24 Jan 2020 07:49:53 GMT-08:00

Sequence and copy number variations in the human CFHR–Factor H gene cluster comprising the complement genes CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and Factor H are linked to the human kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Distinct genetic and chromosomal alterations, deletions, or duplications generate hybrid or mutant CFHR genes, as well as hybrid CFHR–Factor H genes, and alter the FHR and Factor H plasma repertoire. A clear association between the genetic modifications and the pathologic outcome is emerging: CFHR1, CFHR3, and Factor H gene alterations combined with intact CFHR2, CFHR4, and CFHR5 genes are reported in atypical hemolytic uremic syndrome. But alterations in each of the five CFHR genes in the context of an intact Factor H gene are described in C3 glomerulopathy. These genetic modifications influence complement function and the interplay of the five FHR proteins with each other and with Factor H. Understanding how mutant or hybrid FHR proteins, Factor H::FHR hybrid proteins, and altered Factor H, FHR plasma profiles cause pathology is of high interest for diagnosis and therapy.

Whole-Genome Sequencing of Finnish Type 1 Diabetic Siblings Discordant for Kidney Disease Reveals DNA Variants associated with Diabetic Nephropathy

Guo, Jing — Thu, 09 Jan 2020 10:35:16 GMT-08:00

AKI in a Patient with Hemolytic Anemia

Poloni, José Antonio Tesser — Wed, 29 Jan 2020 12:12:21 GMT-08:00

Clinical Images in Nephrology and Dialysis

Perazella, Mark A. — Mon, 06 Jan 2020 05:30:07 GMT-08:00

Is There a Role for Device Therapies in Resistant Hypertension?

Peixoto, Aldo J. — Thu, 02 Jan 2020 12:00:00 GMT-08:00

Introduction to Kidney360

Allon, Michael — Thu, 02 Jan 2020 05:30:08 GMT-08:00

Is There Any Role for Device Therapies in Resistant Hypertension? Commentary

Chang, Tara I. — Thu, 02 Jan 2020 12:00:00 GMT-08:00

Hemocompatibility of Polysulfone Hemodialyzers – Exploratory Studies on Impact of Treatment Modality and Dialyzer Characteristics

Wagner, Stephan — Thu, 09 Jan 2020 05:30:10 GMT-08:00

A Patient with Nephrotic Syndrome and Acute Flank Pain

Perazella, Mark A. — Wed, 29 Jan 2020 12:12:21 GMT-08:00

Is There Any Role for Device Therapies in Resistant Hypertension? PRO

Townsend, Raymond R. — Thu, 02 Jan 2020 05:30:08 GMT-08:00

Potassium Homeostasis, Chronic Kidney Disease, and the Plant-Enriched Diets

Palmer, Biff F. — Wed, 08 Jan 2020 08:30:10 GMT-08:00

There are data demonstrating that ingestion of potassium-rich foods reduces the incidence of stroke, hypertension, nephrolithiasis, and osteoporosis. Dietary-consumption data indicate Westernized diets are high in processed foods, high in sodium content, and low in potassium. In fact, there are data suggesting individuals are not consuming enough potassium in their diet. Although consumption of diets high in plant proteins, fruits, and vegetables—which are excellent sources of potassium—is recognized as healthy and beneficial, individuals with decrements in their kidney function have been advised to avoid these foods. In reviewing the literature that provides the rationale for potassium restriction in patients with reductions in kidney function, it appears there is little direct evidence to support the levels of restriction which are now prescribed. Additionally, there are two new potassium-binding agents which are well tolerated and have been documented to be effective in controlling serum potassium. Therefore, with the new binding agents and the lack of empirical evidence supporting the stringent dietary potassium restrictions, the authors conclude by indicating the pressing need for further research focusing on dietary liberalization of potassium in patients with reductions in kidney function to enhance overall health and well being, to provide them cardiovascular benefits, and to reduce overall risk of mortality through the incorporation of potassium-enriched foods.

The One Thing Clear About Buttonholes, is that Nothing is Clear About Buttonholes

Robb, Maile E. — Mon, 06 Jan 2020 05:30:08 GMT-08:00

Apolipoprotein L1 Gene Testing Comes of Age

Freedman, Barry I. — Wed, 29 Jan 2020 12:12:21 GMT-08:00

Management of Drug-Associated Acute Interstitial Nephritis

Barreto, Erin F. — Wed, 29 Jan 2020 12:12:21 GMT-08:00

Global Dialysis Perspective: Australia

Damasiewicz, Matthew J. — Fri, 03 Jan 2020 05:30:09 GMT-08:00

Global Dialysis Perspective: Korea

Kim, Yong-Soo — Fri, 03 Jan 2020 05:30:09 GMT-08:00

Acute Interstitial Nephritis and Checkpoint Inhibitor Therapy

Manohar, Sandhya — Wed, 29 Jan 2020 12:12:21 GMT-08:00

Can Behavioral Research Improve Transplant Decision-Making? A Mock Offer Study on the Role of Kidney Procurement Biopsies

Stewart, Darren — Mon, 06 Jan 2020 11:17:52 GMT-08:00

Prevention of Bloodstream Infections in Patients Undergoing Hemodialysis

Fisher, Molly — Thu, 05 Dec 2019 06:26:03 GMT-08:00

Bloodstream infections are an important cause of hospitalizations, morbidity, and mortality in patients receiving hemodialysis. Eliminating bloodstream infections in the hemodialysis setting has been the focus of the Centers for Disease Control and Prevention (CDC) Making Dialysis Safer for Patients Coalition and, more recently, the CDC’s partnership with the American Society of Nephrology’s Nephrologists Transforming Dialysis Safety Initiative. The majority of vascular access–associated bloodstream infections occur in patients dialyzing with central vein catheters. The CDC’s core interventions for bloodstream infection prevention are the gold standard for catheter care in the hemodialysis setting and have been proven to be effective in reducing catheter-associated bloodstream infection. However, in the United States hemodialysis catheter–associated bloodstream infections continue to occur at unacceptable rates, possibly because of lapses in adherence to strict aseptic technique, or additional factors not addressed by the CDC’s core interventions. There is a clear need for novel prophylactic therapies. This review highlights the recent advances and includes a discussion about the potential limitations and adverse effects associated with each option.

Racial and Ethnic Variations in Mortality Rates for Patients Undergoing Maintenance Dialysis Treated in US Territories Compared with the US 50 States

Yan, Guofen — Thu, 19 Dec 2019 06:46:20 GMT-08:00

Medical Therapies to Reduce Delayed Graft Function and Improve Long-Term Graft Survival

Lim, Mary Ann — Mon, 16 Dec 2019 08:15:48 GMT-08:00

Exclusion of Persons with Kidney Disease in Trials of Peripheral Artery Disease

Wen, Yumeng — Mon, 30 Dec 2019 06:49:48 GMT-08:00

Lipids and Cardiovascular Risk with CKD

Afshinnia, Farsad — Thu, 12 Dec 2019 08:29:07 GMT-08:00

Disparities in Health Outcomes with Dialysis in the United States Vary by Race

Briggs, Daronta L. — Thu, 19 Dec 2019 06:46:19 GMT-08:00

Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome

Landini, Samuela — Thu, 12 Dec 2019 08:29:08 GMT-08:00

“It’s In Your Genes”

Schaefer, Franz — Thu, 12 Dec 2019 08:29:07 GMT-08:00

Renin-Angiotensin System Blockade after Acute Kidney Injury

Menez, Steven — Mon, 16 Dec 2019 08:15:47 GMT-08:00

Keep Children with CKD Safe from Inappropriate Prescribing

Goldstein, Stuart L. — Thu, 12 Dec 2019 08:29:09 GMT-08:00

Tubular Acidification Defect in Adults with Sickle Cell Disease

Cazenave, Maud — Tue, 10 Dec 2019 07:39:15 GMT-08:00

Ambulatory Hemodialysis-Technology Landscape and Potential for Patient-Centered Treatment

Hojs, Nina — Thu, 14 Nov 2019 06:44:08 GMT-08:00

CKD is a worldwide health problem and the number of patients requiring kidney replacement therapy is rising. In the United States, most patients with ESKD rely on in-center hemodialysis, which is burdensome and does not provide the same long-term benefits as kidney transplantation. Intensive hemodialysis treatments have demonstrated improved clinical outcomes, but its wider adoption is limited by equipment complexity and patient apprehension. Ambulatory devices for hemodialysis offer the potential for self-care treatment outside the clinical setting as well as frequent and prolonged sessions. This article explains the motivation for ambulatory hemodialysis and provides an overview of the necessary features of key technologies that will be the basis for new wearable and implantable devices. Early work by pioneers of hemodialysis is described followed by recent experience using a wearable unit on patients. Finally, ongoing efforts to develop an implantable device for kidney replacement and its potential for implantable hemodialysis are presented.

Alterations of Proximal Tubular Secretion in Autosomal Dominant Polycystic Kidney Disease

Wang, Ke — Fri, 18 Oct 2019 07:10:00 GMT-07:00

Epidemiology of Autosomal Dominant Polycystic Kidney Disease in Olmsted County

Suwabe, Tatsuya — Mon, 02 Dec 2019 08:40:15 GMT-08:00

Primary Care Prescriptions of Potentially Nephrotoxic Medications in Children with CKD

Lefebvre, Claire E. — Thu, 12 Dec 2019 08:29:10 GMT-08:00

Apolipoprotein B, Triglyceride-Rich Lipoproteins, and Risk of Cardiovascular Events in Persons with CKD

Lamprea-Montealegre, Julio Alejandro — Thu, 12 Dec 2019 08:29:09 GMT-08:00

Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI

Hsu, Chi-yuan — Mon, 16 Dec 2019 08:15:48 GMT-08:00

Intraoperative Arterial Pressure Variability and Postoperative Acute Kidney Injury

Park, Sehoon — Mon, 30 Dec 2019 06:49:49 GMT-08:00

Prophylactic Anticoagulation in Adult Patients with Nephrotic Syndrome

Gordon-Cappitelli, Judit — Tue, 01 Oct 2019 10:02:18 GMT-07:00

Genetic Testing for APOL1 Genetic Variants in Clinical Practice

Kopp, Jeffrey B. — Mon, 18 Nov 2019 08:35:30 GMT-08:00

Preserving Kidney Function Instead of Replacing It

Kliger, Alan S. — Tue, 08 Oct 2019 07:00:10 GMT-07:00

Three-Year Outcomes of a Randomized, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients

Huang, Edmund — Mon, 16 Dec 2019 08:15:48 GMT-08:00

Pregnancy in a Kidney Transplant Patient

Ong, Song C. — Mon, 26 Aug 2019 06:39:41 GMT-07:00

GSTM1 Deletion Exaggerates Kidney Injury in Experimental Mouse Models and Confers the Protective Effect of Cruciferous Vegetables in Mice and Humans

Gigliotti, Joseph C. — Thu, 14 Nov 2019 06:44:32 GMT-08:00

Effects of Proximal Tubule Shortening on Protein Excretion in a Lowe Syndrome Model

Gliozzi, Megan L. — Fri, 01 Nov 2019 07:40:31 GMT-07:00

Proximal Tubule Translational Profiling during Kidney Fibrosis Reveals Proinflammatory and Long Noncoding RNA Expression Patterns with Sexual Dimorphism

Wu, Haojia — Thu, 19 Sep 2019 10:26:10 GMT-07:00

Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study

De Vriese, An S. — Fri, 08 Nov 2019 07:45:23 GMT-08:00

Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy

Reinhard, Linda — Mon, 16 Dec 2019 08:27:52 GMT-08:00

A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial

Raphael, Kalani L. — Tue, 17 Dec 2019 08:42:03 GMT-08:00

Periostin Promotes Cell Proliferation and Macrophage Polarization to Drive Repair after AKI

Kormann, Raphaёl — Tue, 05 Nov 2019 07:49:59 GMT-08:00

A Modified Peptide Derived from Goodpasture Autoantigen Arrested and Attenuated Kidney Injuries in a Rat Model of Anti-GBM Glomerulonephritis

Shi, Yue — Wed, 30 Oct 2019 08:48:13 GMT-07:00

Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy

Burbelo, Peter D. — Mon, 16 Dec 2019 08:27:51 GMT-08:00

Deletion in the Cobalamin Synthetase W Domain–Containing Protein 1 Gene Is associated with Congenital Anomalies of the Kidney and Urinary Tract

Kanda, Shoichiro — Fri, 20 Dec 2019 06:33:58 GMT-08:00

Erratum

American Society of Nephrology — Mon, 23 Dec 2019 10:56:17 GMT-08:00

Refining Our Understanding of the PLA2R-Antibody Response in Primary Membranous Nephropathy: Looking Forward, Looking Back

Beck, Laurence H. — Mon, 16 Dec 2019 08:27:51 GMT-08:00

Pilot Trials in Nephrology: Establishing a BASE for Large-Scale Randomized Trials

Neuen, Brendon L. — Tue, 17 Dec 2019 08:42:03 GMT-08:00

This Month's Highlights

American Society of Nephrology — Mon, 23 Dec 2019 10:56:17 GMT-08:00

Single-Cell RNA Sequencing Reveals Renal Endothelium Heterogeneity and Metabolic Adaptation to Water Deprivation

Dumas, Sébastien J. — Mon, 09 Dec 2019 07:20:45 GMT-08:00

Additive Therapeutic Effects of Mesenchymal Stem Cells and IL-37 for Systemic Lupus Erythematosus

Xu, Jianyong — Fri, 11 Oct 2019 08:04:38 GMT-07:00

Financial Neutrality in Organ Donation

Capron, Alexander M. — Mon, 09 Dec 2019 07:20:45 GMT-08:00

Can Dialysis Withdrawal Explain Why White Patients Have Worse Survival than Black Patients?

Norris, Keith C. — Fri, 13 Dec 2019 07:22:32 GMT-08:00

Endothelial Cell Identity, Heterogeneity and Plasticity in the Kidney

Ballermann, Barbara J. — Mon, 09 Dec 2019 07:20:44 GMT-08:00

When Less Becomes More: Life and Losses without the ‘Roids’?

Wong, Germaine — Wed, 18 Dec 2019 08:22:23 GMT-08:00

Racial/Ethnic Differences in Dialysis Discontinuation and Survival after Hospitalization for Serious Conditions among Patients on Maintenance Dialysis

Agunbiade, Abdulkareem — Fri, 13 Dec 2019 07:22:32 GMT-08:00

Clinical Pig Kidney Xenotransplantation: How Close Are We?

Cooper, David K. C. — Mon, 02 Dec 2019 08:42:19 GMT-08:00

Patients with ESKD who would benefit from a kidney transplant face a critical and continuing shortage of kidneys from deceased human donors. As a result, such patients wait a median of 3.9 years to receive a donor kidney, by which time approximately 35% of transplant candidates have died while waiting or have been removed from the waiting list. Those of blood group B or O may experience a significantly longer waiting period. This problem could be resolved if kidneys from genetically engineered pigs offered an alternative with an acceptable clinical outcome. Attempts to accomplish this have followed two major paths: deletion of pig xenoantigens, as well as insertion of “protective” human transgenes to counter the human immune response. Pigs with up to nine genetic manipulations are now available. In nonhuman primates, administering novel agents that block the CD40/CD154 costimulation pathway, such as an anti-CD40 mAb, suppresses the adaptive immune response, leading to pig kidney graft survival of many months without features of rejection (experiments were terminated for infectious complications). In the absence of innate and adaptive immune responses, the transplanted pig kidneys have generally displayed excellent function. A clinical trial is anticipated within 2 years. We suggest that it would be ethical to offer a pig kidney transplant to selected patients who have a life expectancy shorter than the time it would take for them to obtain a kidney from a deceased human donor. In the future, the pigs will also be genetically engineered to control the adaptive immune response, thus enabling exogenous immunosuppressive therapy to be significantly reduced or eliminated.

Economic Evaluation of Extending Medicare Immunosuppressive Drug Coverage for Kidney Transplant Recipients in the Current Era

Kadatz, Matthew — Fri, 08 Nov 2019 07:45:23 GMT-08:00

Early Steroid Withdrawal in Deceased-Donor Kidney Transplant Recipients with Delayed Graft Function

Bae, Sunjae — Wed, 18 Dec 2019 08:22:23 GMT-08:00

Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD

Locatelli, Francesco — Fri, 16 Aug 2019 05:18:49 GMT-07:00

Complement Activation and Thrombotic Microangiopathies

Palomo, Marta — Wed, 06 Nov 2019 10:55:51 GMT-08:00

Varying Association of Extended Hours Dialysis with Quality of Life

Smyth, Brendan — Thu, 31 Oct 2019 11:05:18 GMT-07:00

APOL1 Nephropathy Risk Alleles and Risk of Sepsis in Blacks

Chaudhary, Ninad S. — Fri, 08 Nov 2019 07:28:00 GMT-08:00

Change in Dyslipidemia with Declining Glomerular Filtration Rate and Increasing Proteinuria in Children with CKD

Saland, Jeffrey M. — Mon, 11 Nov 2019 08:13:34 GMT-08:00

Monitoring Complement Activation

Fakhouri, Fadi — Wed, 06 Nov 2019 10:55:50 GMT-08:00

Gaps in Care among Veterans with Urinary Stone Disease

Hsi, Ryan S. — Mon, 11 Nov 2019 08:13:34 GMT-08:00

Fibrillary Glomerulonephritis

Andeen, Nicole K. — Mon, 04 Nov 2019 07:22:03 GMT-08:00

Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease–Related Medications in Veterans

Song, Shen — Mon, 11 Nov 2019 08:13:35 GMT-08:00

Acute Kidney Injury with Immune Checkpoint Inhibitors

Carlos, Christopher A. — Thu, 31 Oct 2019 11:05:19 GMT-07:00

APOL1 Nephropathy Risk Variant Associations with Diseases beyond the Kidney

Ma, Lijun — Fri, 08 Nov 2019 07:28:00 GMT-08:00

How Extended Hemodialysis Treatment Time Can Affect Patient Quality of Life

Wilk, Adam S. — Thu, 31 Oct 2019 11:05:19 GMT-07:00

Trends in Peritoneal Dialysis Use in the United States after Medicare Payment Reform

Sloan, Caroline E. — Thu, 21 Nov 2019 08:40:21 GMT-08:00

Public Policy and Patient Choice of Dialysis Modality

Hartwell, Lori — Thu, 21 Nov 2019 08:40:20 GMT-08:00

Advancing American Kidney Health

Nissenson, Allen R. — Fri, 08 Nov 2019 07:28:00 GMT-08:00

A Patient’s Perspective on Advancing American Kidney Health Initiative

Knight, Richard — Wed, 06 Nov 2019 10:55:50 GMT-08:00

A Call to Action for the Kidney Community

Bieber, Scott D. — Thu, 07 Nov 2019 05:56:48 GMT-08:00

Advancing American Kidney Health

Kossmann, Robert J. — Fri, 08 Nov 2019 07:28:00 GMT-08:00

Transforming Care for Patients and Providers

Watnick, Suzanne — Fri, 08 Nov 2019 07:28:00 GMT-08:00

A Vision for Advancing American Kidney Health

Patel, Sandeep — Tue, 05 Nov 2019 07:41:47 GMT-08:00

July 10, 2019, A Day to Be Remembered

Scott, Nancy — Wed, 06 Nov 2019 10:55:50 GMT-08:00

Advancing American Kidney Health

Mehrotra, Rajnish — Tue, 05 Nov 2019 07:41:48 GMT-08:00

Preparing the Nephrology Workforce for the Transformation to Value-Based Kidney Care

Tummalapalli, Sri Lekha — Thu, 07 Nov 2019 05:56:48 GMT-08:00

Winning the War on Kidney Disease

Rosenberg, Mark E. — Tue, 05 Nov 2019 07:41:48 GMT-08:00

The Incidence, Causes, and Risk Factors of Acute Kidney Injury in Patients Receiving Immune Checkpoint Inhibitors

Seethapathy, Harish — Thu, 31 Oct 2019 11:05:19 GMT-07:00

Quantifying Donor Effects on Transplant Outcomes Using Kidney Pairs from Deceased Donors

Kerr, Kathleen F. — Fri, 01 Nov 2019 06:11:07 GMT-07:00

Think Twice before Postponing Chronic Dialysis in Children

Preka, Evgenia — Thu, 24 Oct 2019 04:50:02 GMT-07:00

Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury

Inoue, Kazunori — Wed, 11 Sep 2019 06:30:46 GMT-07:00

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research

Denburg, Michelle R. — Fri, 15 Nov 2019 06:06:26 GMT-08:00

APOL1 Kidney Risk Variants Induce Cell Death via Mitochondrial Translocation and Opening of the Mitochondrial Permeability Transition Pore

Shah, Shrijal S. — Thu, 26 Sep 2019 05:53:59 GMT-07:00

Anti-donor MHC Class II Alloantibody Induces Glomerular Injury in Mouse Renal Allografts Subjected to Prolonged Cold Ischemia

Gorbacheva, Victoria — Wed, 09 Oct 2019 06:26:09 GMT-07:00

Erratum

American Society of Nephrology — Fri, 29 Nov 2019 10:00:25 GMT-08:00

Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI

Chiba, Takuto — Tue, 01 Oct 2019 10:04:04 GMT-07:00

Exploring Care Attributes of Nephrologists Ranking Favorably on Measures of Value

Brady, Brian M. — Thu, 14 Nov 2019 06:44:31 GMT-08:00

Proximal Tubule–Derived Amphiregulin Amplifies and Integrates Profibrotic EGF Receptor Signals in Kidney Fibrosis

Kefaloyianni, Eirini — Fri, 01 Nov 2019 07:40:30 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 29 Nov 2019 10:00:25 GMT-08:00

Authors’ Reply

Winnicki, Erica — Thu, 24 Oct 2019 04:50:02 GMT-07:00

TBC1D8B Mutations Implicate RAB11-Dependent Vesicular Trafficking in the Pathogenesis of Nephrotic Syndrome

Kampf, Lina L. — Fri, 15 Nov 2019 06:06:27 GMT-08:00

Racial Differences and Factors Associated with Pregnancy in ESKD Patients on Dialysis in the United States

Shah, Silvi — Wed, 25 Sep 2019 07:13:11 GMT-07:00

Race, Pregnancy, and ESKD

Toth-Manikowski, Stephanie M. — Mon, 04 Nov 2019 07:24:29 GMT-08:00

Finding That Needle in the Haystack: Computable Phenotypes

Glenn, Dorey — Fri, 15 Nov 2019 06:06:26 GMT-08:00

Competing Risk Modeling: Time to Put it in Our Standard Analytical Toolbox

Li, Liang — Fri, 15 Nov 2019 06:06:27 GMT-08:00

Value-Based Kidney Care: Aligning Metrics and Incentives to Improve the Health of People with Kidney Disease

Garimella, Pranav S. — Thu, 14 Nov 2019 06:44:31 GMT-08:00

Identification of Acer2 as a First Susceptibility Gene for Lithium-Induced Nephrogenic Diabetes Insipidus in Mice

de Groot, Theun — Thu, 26 Sep 2019 05:53:58 GMT-07:00

Prioritizing Functional Goals as We Rebuild the Kidney

Humphreys, Benjamin D. — Fri, 01 Nov 2019 07:40:31 GMT-07:00

Looking Back 50 Years at the Biology of Mankind in Space: The Renal-Cardiovascular Fluid Shift Conundrum

Fine, Leon G. — Fri, 01 Nov 2019 07:40:31 GMT-07:00

Kidney Regeneration in Later-Stage Mouse Embryos via Transplanted Renal Progenitor Cells

Yamanaka, Shuichiro — Mon, 23 Sep 2019 08:22:20 GMT-07:00

Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome

Zuber, Julien — Tue, 01 Oct 2019 10:04:04 GMT-07:00

Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients

Ezekian, Brian — Mon, 28 Oct 2019 09:58:21 GMT-07:00

Optimizing Use of Deceased Donor Kidneys: Organ Waste While We Continue to Wait

Bensouda, Melissa — Thu, 17 Oct 2019 07:32:12 GMT-07:00

No Time to Wait

Davis, Scott — Thu, 17 Oct 2019 07:32:12 GMT-07:00

Survival and Kidney Outcomes of Children with an Early Diagnosis of Posterior Urethral Valves

Herbst, Katherine W. — Thu, 03 Oct 2019 06:59:36 GMT-07:00

Frailty and CKD

Delgado, Cynthia — Fri, 18 Oct 2019 07:10:00 GMT-07:00

Sex and the Incidence and Prevalence of Kidney Disease

Tomlinson, Laurie A. — Thu, 24 Oct 2019 04:51:53 GMT-07:00

A Validation Study of Employment Status in Late-Stage CKD

Kutner, Nancy G. — Fri, 09 Aug 2019 05:43:13 GMT-07:00

A Donor Utilization Index to Assess the Utilization and Discard of Deceased Donor Kidneys Perceived as High Risk

Brennan, Corey — Thu, 17 Oct 2019 07:32:12 GMT-07:00

Genetic and Environmental Influences on the Correlations between Traits of Metabolic Syndrome and CKD

Chen, Xu — Tue, 10 Sep 2019 07:05:02 GMT-07:00

Safe and Effective Management of Pain in People with CKD

Davison, Sara N. — Fri, 11 Oct 2019 07:57:27 GMT-07:00

Correction

American Society of Nephrology — Thu, 26 Sep 2019 05:40:23 GMT-07:00

Estimated Glomerular Filtration Rate Decline and Incident Frailty in Older Adults

Guerville, Florent — Fri, 18 Oct 2019 07:10:01 GMT-07:00

Sensitivity and Specificity of Pathologic Findings to Diagnose Lupus Nephritis

Kudose, Satoru — Fri, 25 Oct 2019 07:15:23 GMT-07:00

Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR

Novick, Tessa K. — Thu, 03 Oct 2019 06:59:36 GMT-07:00

Sex Differences in Kidney Replacement Therapy Initiation and Maintenance

Antlanger, Marlies — Thu, 24 Oct 2019 04:51:53 GMT-07:00

Serum Calcification Propensity and Clinical Events in CKD

Bundy, Joshua D. — Mon, 28 Oct 2019 10:00:16 GMT-07:00

How Does CREDENCE Inform Best Use of SGLT2 Inhibitors in CKD?

Neumiller, Joshua J. — Tue, 01 Oct 2019 10:02:18 GMT-07:00

CKD in Native Hawaiians and Pacific Islanders

Naʻai, David — Mon, 09 Sep 2019 05:18:27 GMT-07:00

Foamy Urine

Khitan, Zeid J. — Tue, 01 Oct 2019 10:02:18 GMT-07:00

Treatment of Growth Retardation in a Child with CKD

Stonebrook, Emily — Fri, 26 Jul 2019 07:26:36 GMT-07:00

Hypertension in a Pregnant Patient: How I Treat

August, Phyllis — Wed, 03 Jul 2019 08:04:11 GMT-07:00

Preoperative Noncoronary Cardiovascular Assessment and Management of Kidney Transplant Candidates

Baman, Jayson Rakesh — Wed, 25 Sep 2019 07:02:55 GMT-07:00

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.

Risk Factors for 1-Year Graft Loss After Kidney Transplantation

Foroutan, Farid — Fri, 20 Sep 2019 07:24:21 GMT-07:00

Serum Phosphate and Microvascular Function in a Population-Based Cohort

Ginsberg, Charles — Fri, 20 Sep 2019 07:24:20 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Thu, 31 Oct 2019 10:00:31 GMT-07:00

Influence of Mortality on Estimating the Risk of Kidney Failure in People with Stage 4 CKD

Ravani, Pietro — Fri, 20 Sep 2019 07:24:27 GMT-07:00

Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function

Thomas, Linto — Tue, 13 Aug 2019 06:35:01 GMT-07:00

Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD: Accurate or Not?

Collins, Michael G. — Wed, 09 Oct 2019 06:26:10 GMT-07:00

New Ways of Finding New Genes for Old Diseases

Sandford, Richard N. — Thu, 10 Oct 2019 04:07:17 GMT-07:00

Fistula Interventions: Less Is More

Lok, Charmaine E. — Mon, 14 Oct 2019 07:33:28 GMT-07:00

Tracking HLA Antibody Changes among Kidney Waitlist Candidates: One Protocol May Not Fit All

Jackson, Annette M. — Fri, 25 Oct 2019 07:14:13 GMT-07:00

ALG9 Mutation Carriers Develop Kidney and Liver Cysts

Besse, Whitney — Thu, 08 Aug 2019 06:51:48 GMT-07:00

In Remembrance of Thomas F. Ferris, MD, Former ASN President (1987–1988)

Hostetter, Thomas — Fri, 11 Oct 2019 08:04:39 GMT-07:00

Another Tool in the Fight Against Phosphate Toxicity: Where Will It Fit and What Does It Tell Us about Phosphate Homeostasis?

Lederer, Eleanor — Fri, 11 Oct 2019 08:04:39 GMT-07:00

Authors’ Reply

Wong, Germaine — Wed, 09 Oct 2019 06:26:10 GMT-07:00

Integrin-Linked Kinase Deficiency in Collecting Duct Principal Cell Promotes Necroptosis of Principal Cell and Contributes to Kidney Inflammation and Fibrosis

Huang, Ming — Fri, 25 Oct 2019 07:14:12 GMT-07:00

Single-Cell Transcriptomic Map of the Human and Mouse Bladders

Yu, Zhenyuan — Wed, 28 Aug 2019 07:31:44 GMT-07:00

Tolerogenic Dendritic Cells Attenuate Experimental Autoimmune Antimyeloperoxidase Glomerulonephritis

Odobasic, Dragana — Fri, 23 Aug 2019 08:29:46 GMT-07:00

Background Because of their capacity to induce antigen-specific immunosuppression, tolerogenic dendritic cells are a promising tool for treatment of autoimmune conditions, such as GN caused by autoimmunity against myeloperoxidase (MPO).

Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study

Lee, Timmy — Mon, 14 Oct 2019 07:33:28 GMT-07:00

Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease

Ma, Ming — Mon, 26 Aug 2019 07:14:51 GMT-07:00

Piperacillin/Tazobactam and Antibiotic-Associated Acute Kidney Injury in Critically Ill Children

Joyce, Emily L. — Mon, 09 Sep 2019 05:21:13 GMT-07:00

AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis

Chow, Bryna S. M. — Wed, 11 Sep 2019 06:30:46 GMT-07:00

Synergistic Genetic Interactions between Pkhd1 and Pkd1 Result in an ARPKD-Like Phenotype in Murine Models

Olson, Rory J. — Mon, 19 Aug 2019 08:11:55 GMT-07:00

Protection of Cystinotic Mice by Kidney-Specific Megalin Ablation Supports an Endocytosis-Based Mechanism for Nephropathic Cystinosis Progression

Janssens, Virginie — Mon, 23 Sep 2019 08:22:21 GMT-07:00

Iron Chelation as a Potential Therapeutic Strategy for AKI Prevention

Sharma, Shreyak — Wed, 25 Sep 2019 07:13:10 GMT-07:00

AKI remains a major public health concern. Despite years of investigation, no intervention has been demonstrated to reliably prevent AKI in humans. Thus, development of novel therapeutic targets is urgently needed. An important role of iron in the pathophysiology of AKI has been recognized for over three decades. When present in excess and in nonphysiologic labile forms, iron is toxic to the kidneys and multiple other organs, whereas iron chelation is protective across a broad spectrum of insults. In humans, small studies have investigated iron chelation as a novel therapeutic strategy for prevention of AKI and extrarenal acute organ injury, and have demonstrated encouraging initial results. In this review, we examine the existing data on iron chelation for AKI prevention in both animal models and human studies. We discuss practical considerations for future clinical trials of AKI prevention using iron chelators, including selection of the ideal clinical setting, patient population, iron chelating agent, and dosing regimen. Finally, we compare the key differences among the currently available iron chelators, including pharmacokinetics, routes of administration, and adverse effects.

Intradialytic Cerebral Hypoperfusion as Mechanism for Cognitive Impairment in Patients on Hemodialysis

Wolfgram, Dawn F. — Wed, 11 Sep 2019 06:30:46 GMT-07:00

The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis. Patients on hemodialysis may be at increased risk for cerebral ischemic injury disease due to vasculopathy associated with ESKD and from their comorbid diseases, such as hypertension and diabetes. This review focuses on the intradialytic cerebral hypoperfusion that can occur during routine hemodialysis due to the circulatory stress of hemodialysis. This includes a review of current methods used to monitor intradialytic cerebral perfusion and the structural and functional cognitive outcomes that have been associated with changes in intradialytic cerebral perfusion. Monitoring of intradialytic cerebral perfusion may become clinically relevant as nephrologists try to avoid the cognitive complications seen with hemodialysis. Identifying the appropriate methods to assess risk for cerebral ischemic injury and the relationship of intradialytic cerebral hypoperfusion to cognitive outcomes will help inform the decision to use intradialytic cerebral perfusion monitoring in the clinical setting as part of a strategy to prevent cognitive decline.

Pretransplant Kinetics of Anti-HLA Antibodies in Patients on the Waiting List for Kidney Transplantation

Togninalli, Matteo — Fri, 25 Oct 2019 07:14:13 GMT-07:00

New Trends in Regenerative Medicine: Reprogramming and Reconditioning

Goligorsky, Michael S. — Fri, 20 Sep 2019 07:24:26 GMT-07:00

Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program

Neuen, Brendon L. — Tue, 17 Sep 2019 06:24:04 GMT-07:00

Serious Illness Treatment Preferences for Older Adults with Advanced CKD

Baddour, Nicolas Awad — Wed, 11 Sep 2019 06:30:45 GMT-07:00

The Acute Dialysis Orders Objective Structured Clinical Examination (OSCE)

Prince, Lisa K. — Tue, 13 Aug 2019 06:30:31 GMT-07:00

Correction

American Society of Nephrology — Wed, 22 May 2019 08:23:43 GMT-07:00

Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts

Wang, Wei — Thu, 15 Aug 2019 08:08:35 GMT-07:00

NSAIDs and Nephrotic Syndrome

Mérida, Evangelina — Thu, 15 Aug 2019 08:08:34 GMT-07:00

Imaging as a Noninvasive Tool for Evaluating Interstitial Fibrosis in Kidney Allografts

Poggio, Emilio D. — Thu, 15 Aug 2019 08:08:35 GMT-07:00

Nephrology Advanced Practitioners in the United States, 2010-2018

Zuber, Kim — Thu, 11 Jul 2019 06:35:16 GMT-07:00

Association of Acute Increases in Plasma Creatinine after Renin-Angiotensin Blockade with Subsequent Outcomes

Fu, Edouard L. — Thu, 08 Aug 2019 06:51:32 GMT-07:00

An Electronic CKD Phenotype: A Step Forward in Improving Kidney Care

Tummalapalli, Sri Lekha — Mon, 12 Aug 2019 06:00:10 GMT-07:00

Psychiatric Problems Faced by Patients on Dialysis

Couch, Sasha — Thu, 22 Aug 2019 06:46:09 GMT-07:00

Psychiatric Illness and Mortality in Hospitalized ESKD Dialysis Patients

Kimmel, Paul L. — Thu, 22 Aug 2019 06:46:09 GMT-07:00

Burden of Psychiatric Illness in Patients with ESKD

Fischer, Michael J. — Thu, 22 Aug 2019 06:46:09 GMT-07:00

Biosimilars—Emerging Role in Nephrology

Wish, Jay B. — Mon, 06 Aug 2018 05:55:06 GMT-07:00

The Food and Drug Administration (FDA) defines a “biosimilar” agent as a biologic that is highly similar to the reference or originator biologic product notwithstanding minor differences in clinically inactive components with no clinically meaningful differences in terms of the safety, purity, and potency. The advantage of biosimilars is that they are usually about 15%–30% less expensive than the reference product, which results in system-wide cost savings and increased patient access. Because biologic drugs are produced by living organisms, they are by nature heterogeneous and identical copies cannot be made, unlike generic versions of small-molecule drugs. Proposed biosimilars must undergo a rigorous evaluation process to demonstrate a high degree of structural and functional similarity with the reference biologic. Once that is confirmed, a stepwise process of comparison with the reference agent with regard to animal trials, pharmacokinetics/pharmacodynamics, immunogenicity, and human efficacy/safety is conducted. The experience with biosimilars in other highly regulated markets where patent protection for originator biologics is not as robust as in the United States has been favorable in terms of safety, efficacy, and cost savings. An FDA approval pathway was created in 2009 to expedite the approval of biosimilars; as of early 2018 nine agents had been approved through that pathway, none in nephrology. The first United States biosimilar epoetin was approved on May 15, 2018, but does not have an interchangeability designation, meaning that prescribers must specifically write for the biosimilar product for patients to receive it. Given the unfamiliarity of biosimilars within the nephrology community it is recommended that educational programs be developed to address this unmet need and for research to be conducted addressing the perceptual, clinical, and economic effect of biosimilars on our patients.

Biomarkers to Predict Progression in IgA Nephropathy

Cheung, Chee Kay — Wed, 11 Sep 2019 05:09:38 GMT-07:00

Can Dietary Patterns Modify Risk for CKD?

Hu, Emily A. — Tue, 24 Sep 2019 07:39:20 GMT-07:00

Diet Patterns and Kidney Disease

Lennon, Michael J. — Tue, 24 Sep 2019 07:39:21 GMT-07:00

A Technology Roadmap for Innovative Approaches to Kidney Replacement Therapies

Bonventre, Joseph V. — Fri, 27 Sep 2019 05:40:12 GMT-07:00

The number of patients dialyzed for ESKD exceeds 500,000 in the United States and more than 2.6 million people worldwide, with the expectation that the worldwide number will double by 2030. The human cost of health and societal financial cost of ESKD is substantial. Dialytic therapy is associated with an unacceptably high morbidity and mortality rate and poor quality of life. Although innovation in many areas of science has been transformative, there has been little innovation in dialysis or alternatives for kidney replacement therapy (KRT) since its introduction approximately 70 years ago. Advances in kidney biology, stem cells and kidney cell differentiation protocols, biomaterials, sensors, nano/microtechnology, sorbents and engineering, and interdisciplinary approaches and collaborations can lead to disruptive innovation. The Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and the US Food and Drug Administration, has convened a multidisciplinary group to create a technology roadmap for innovative approaches to KRT to address patients’ needs. The Roadmap is a living document. It identifies the design criteria that must be considered to replace the myriad functions of the kidney, as well as scientific, technical, regulatory, and payor milestones required to commercialize and provide patient access to KRT alternatives. Various embodiments of potential solutions are discussed, but the Roadmap is agnostic to any particular solution set. System enablers are identified, including vascular access, biomaterial development, biologic and immunologic modulation, function, and safety monitoring. Important Roadmap supporting activities include regulatory alignment and innovative financial incentives and payment pathways. The Roadmap provides estimated timelines for replacement of specific kidney functions so that approaches can be conceptualized in ways that are actionable and attract talented innovators from multiple disciplines. The Roadmap has been used to guide the selection of KidneyX prizes for innovation in KRT.

Peritoneal Dialysis Patient Outcomes under the Medicare Expanded Dialysis Prospective Payment System

Young, Eric W. — Thu, 12 Sep 2019 06:09:24 GMT-07:00

Dietary Phosphorus and FGF23

Hill Gallant, Kathleen M. — Fri, 13 Sep 2019 06:59:38 GMT-07:00

Is Hypertension Following Donor Nephrectomy Cause For Elevated Living Donor Kidney Function Concern?

Asch, William S. — Thu, 19 Sep 2019 10:18:47 GMT-07:00

The Association of Fenofibrate with Kidney Tubular Injury in a Subgroup of Participants in the ACCORD Trial

Chauhan, Kinsuk — Tue, 13 Aug 2019 06:30:30 GMT-07:00

Short-Term Effects of Very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients

Tsai, Wan-Chuan — Fri, 13 Sep 2019 06:59:38 GMT-07:00

Self-Reported Incident Hypertension and Long-Term Kidney Function in Living Kidney Donors Compared with Healthy Nondonors

Holscher, Courtenay M. — Thu, 19 Sep 2019 10:18:48 GMT-07:00

Correction

American Society of Nephrology — Fri, 23 Aug 2019 08:29:28 GMT-07:00

Incidence of ESKD and Mortality among Children with Congenital Heart Disease after Cardiac Surgery

Parikh, Chirag R. — Mon, 09 Sep 2019 05:18:27 GMT-07:00

Healthy Dietary Patterns and Incidence of CKD

Bach, Katrina E. — Tue, 24 Sep 2019 07:39:21 GMT-07:00

Kidney Support in Children using an Ultrafiltration Device

Menon, Shina — Wed, 28 Aug 2019 07:01:44 GMT-07:00

Post-PIVOTAL Iron Dosing with Maintenance Hemodialysis

Collister, David — Mon, 10 Jun 2019 07:37:58 GMT-07:00

Interoperability of Electronic Health Information and Care of Dialysis Patients in the United States

Sutton, Paul R. — Fri, 06 Sep 2019 08:25:05 GMT-07:00

Real World Data and Evidence: Support for Drug Approval

Thompson, Aliza M. — Fri, 06 Sep 2019 08:25:05 GMT-07:00

Persistent Disparities in Preemptive Kidney Transplantation

Purnell, Tanjala S. — Thu, 26 Sep 2019 05:40:23 GMT-07:00

Circulating Advanced Glycation Endproducts and Long-Term Risk of Cardiovascular Mortality in Kidney Transplant Recipients

Sotomayor, Camilo G. — Tue, 17 Sep 2019 06:24:04 GMT-07:00

Trends in Disparities in Preemptive Kidney Transplantation in the United States

King, Kristen L. — Thu, 26 Sep 2019 05:40:23 GMT-07:00

Infection-Related Mortality in Recipients of a Kidney Transplant in Australia and New Zealand

Chan, Samuel — Tue, 27 Aug 2019 10:42:34 GMT-07:00

Intravenous Iron Use in the Care of Patients with Kidney Disease

Macdougall, Iain C. — Fri, 07 Jun 2019 08:33:52 GMT-07:00

Vaccinating the Patient with ESKD

Khan, Sana F. — Mon, 01 Jul 2019 09:00:39 GMT-07:00

KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis

Wen, Yi — Tue, 23 Jul 2019 07:31:25 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Mon, 30 Sep 2019 10:00:31 GMT-07:00

APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis

Grams, Morgan E. — Mon, 05 Aug 2019 07:09:32 GMT-07:00

Burden of CKD and Cardiovascular Disease on Life Expectancy and Health Service Utilization: a Cohort Study of Hong Kong Chinese Hypertensive Patients

Wan, Eric Yuk Fai — Fri, 06 Sep 2019 08:28:26 GMT-07:00

TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, and Motility

Farmer, Louise K. — Thu, 15 Aug 2019 07:51:34 GMT-07:00

Anti-CD45RB Antibody Therapy Attenuates Renal Ischemia-Reperfusion Injury by Inducing Regulatory B Cells

Fang, Taishi — Thu, 11 Jul 2019 06:35:30 GMT-07:00

From People to Lab Rats to People—Study of Exercise in CKD

Johansen, Kirsten L. — Mon, 09 Sep 2019 05:21:13 GMT-07:00

A Toolbox to Characterize Human Induced Pluripotent Stem Cell–Derived Kidney Cell Types and Organoids

Vanslambrouck, Jessica M. — Fri, 06 Sep 2019 08:28:26 GMT-07:00

Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury

Xu, Leyuan — Wed, 17 Jul 2019 07:58:21 GMT-07:00

Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)

Avin, Keith G. — Mon, 09 Sep 2019 05:21:13 GMT-07:00

Tissue-Resident Macrophages Promote Renal Cystic Disease

Zimmerman, Kurt A. — Tue, 23 Jul 2019 07:31:24 GMT-07:00

Mitochondria Permeability Transition versus Necroptosis in Oxalate-Induced AKI

Mulay, Shrikant Ramesh — Thu, 11 Jul 2019 06:35:30 GMT-07:00

Glomerular Function and Structural Integrity Depend on Hyaluronan Synthesis by Glomerular Endothelium

van den Berg, Bernard M. — Mon, 15 Jul 2019 04:33:32 GMT-07:00

Glomerular Immunodeposits of Patients with IgA Nephropathy Are Enriched for IgG Autoantibodies Specific for Galactose-Deficient IgA1

Rizk, Dana V. — Fri, 23 Aug 2019 08:29:46 GMT-07:00

Machine Learning Comes to Nephrology

Lemley, Kevin V. — Thu, 05 Sep 2019 06:03:15 GMT-07:00

Deep Learning–Based Histopathologic Assessment of Kidney Tissue

Hermsen, Meyke — Thu, 05 Sep 2019 06:03:15 GMT-07:00

CKD: A Call for an Age-Adapted Definition

Delanaye, Pierre — Tue, 10 Sep 2019 06:48:07 GMT-07:00

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2. This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2. Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

Effects of Selonsertib in Patients with Diabetic Kidney Disease

Chertow, Glenn M. — Tue, 10 Sep 2019 06:48:08 GMT-07:00

Computational Segmentation and Classification of Diabetic Glomerulosclerosis

Ginley, Brandon — Thu, 05 Sep 2019 06:03:14 GMT-07:00

Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Salem, Rany M. — Thu, 19 Sep 2019 10:26:09 GMT-07:00

Biologic Underpinnings of Type 1 Diabetic Kidney Disease

Sedor, John R. — Thu, 19 Sep 2019 10:26:08 GMT-07:00

Modification of eGFR-Based CKD Definitions: Perfect, or Enemy of the Good?

Chertow, Glenn M. — Tue, 10 Sep 2019 06:48:07 GMT-07:00

Does eGFR by Any Number Mean the Same?

Wesson, Donald E. — Tue, 10 Sep 2019 06:48:07 GMT-07:00

Transplantation of Kidneys from HCV Viremic Donors in the United States: A Missed Opportunity to Inform Clinical Decision Making and Health Policy

Gill, John S. — Thu, 12 Sep 2019 06:05:34 GMT-07:00

National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys

Potluri, Vishnu S. — Thu, 12 Sep 2019 06:05:35 GMT-07:00

Extracorporeal Removal of Poisons and Toxins

King, Joshua David — Thu, 22 Aug 2019 06:46:10 GMT-07:00

Extracorporeal therapies have been used to remove toxins from the body for over 50 years and have a greater role than ever before in the treatment of poisonings. Improvements in technology have resulted in increased efficacy of removing drugs and other toxins with hemodialysis, and newer extracorporeal therapy modalities have expanded the role of extracorporeal supportive care of poisoned patients. However, despite these changes, for at least the past three decades the most frequently dialyzed poisons remain salicylates, toxic alcohols, and lithium; in addition, the extracorporeal treatment of choice for therapeutic removal of nearly all poisonings remains intermittent hemodialysis. For the clinician, consideration of extracorporeal therapy in the treatment of a poisoning depends upon the characteristics of toxins amenable to extracorporeal removal (e.g., molecular mass, volume of distribution, protein binding), choice of extracorporeal treatment modality for a given poisoning, and when the benefit of the procedure justifies additive risk. Given the relative rarity of poisonings treated with extracorporeal therapies, the level of evidence for extracorporeal treatment of poisoning is not robust; however, extracorporeal treatment of a number of individual toxins have been systematically reviewed within the current decade by the Extracorporeal Treatment in Poisoning workgroup, which has published treatment recommendations with an improved evidence base. Some of these recommendations are discussed, as well as management of a small number of relevant poisonings where extracorporeal therapy use may be considered.

Development and Validation of a Pragmatic Electronic Phenotype for CKD

Norton, Jenna M. — Mon, 12 Aug 2019 06:00:11 GMT-07:00

Methods for Assessing Longitudinal Biomarkers of Time-to-Event Outcomes in CKD

Liu, Qian — Thu, 15 Aug 2019 08:08:33 GMT-07:00

Family Perceptions of Quality of End-of-Life Care for Veterans with Advanced CKD

Richards, Claire A. — Thu, 29 Aug 2019 05:42:19 GMT-07:00

The Role of Volume Regulation and Thermoregulation in AKI during Marathon Running

Mansour, Sherry G. — Wed, 14 Aug 2019 07:40:13 GMT-07:00

Secular Trends in Incidence, Modality and Mortality with Dialysis Receiving AKI in Children in Ontario

Chanchlani, Rahul — Fri, 23 Aug 2019 08:29:29 GMT-07:00

Risk of Nephrotic Syndrome for Non-Steroidal Anti-Inflammatory Drug Users

Bakhriansyah, Mohammad — Thu, 15 Aug 2019 08:08:34 GMT-07:00

Shared Hemodialysis Care

Wilkie, Martin — Fri, 26 Jul 2019 07:26:37 GMT-07:00

Role of the Nephro-Hospitalist

Yau, Timothy T. — Fri, 09 Aug 2019 05:43:13 GMT-07:00

Barriers to the Professional Advancement of Women in Nephrology

O’Lone, Emma — Fri, 26 Jul 2019 07:26:37 GMT-07:00

A Case of Drug-Induced Proximal Tubular Dysfunction

Hall, Andrew M. — Mon, 10 Jun 2019 07:37:57 GMT-07:00

Recurrent Calcium Kidney Stones

Beara-Lasic, Lada — Thu, 20 Jun 2019 05:45:26 GMT-07:00

GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-κB Pathway

Zambrano, Sonia — Mon, 08 Jul 2019 07:36:16 GMT-07:00

Mesangial Cells: The Tuft Guys of Glomerular Development

Marciano, Denise K. — Mon, 12 Aug 2019 06:04:51 GMT-07:00

Clinical Trial Data Sharing: The Time Is Now

Briggs, Josephine P. — Tue, 13 Aug 2019 06:35:02 GMT-07:00

Contribution of Coiled-Coil Assembly to Ca2+/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes

Polat, Onur K. — Tue, 02 Jul 2019 08:27:07 GMT-07:00

A Novel Role for GATA3 in Mesangial Cells in Glomerular Development and Injury

Grigorieva, Irina V. — Mon, 12 Aug 2019 06:04:51 GMT-07:00

Contributions of Rare Gene Variants to Familial and Sporadic FSGS

Wang, Minxian — Mon, 15 Jul 2019 04:33:32 GMT-07:00

The Role of the EGF Receptor in Sex Differences in Kidney Injury

Zhang, Ming-Zhi — Wed, 10 Jul 2019 06:16:04 GMT-07:00

Analysis of Other Confounding Factors Is Mandatory before Considering That Long-Acting Erythropoiesis Stimulating Agents Are Deleterious to Patients on Dialysis

Rostoker, Guy — Fri, 16 Aug 2019 05:39:06 GMT-07:00

Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression

Nelson, Tracy — Mon, 12 Aug 2019 06:04:52 GMT-07:00

The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus

Chiusa, Manuel — Mon, 05 Aug 2019 07:09:33 GMT-07:00

ESA Resistance May Be a Potential Confounder for Mortality among Different ESA Types

Tanaka, Mototsugu — Fri, 16 Aug 2019 05:39:06 GMT-07:00

Authors’ Reply

Sakaguchi, Yusuke — Fri, 16 Aug 2019 05:39:05 GMT-07:00

Another Example of Race Disparities in the US Healthcare System

Grubbs, Vanessa — Tue, 06 Aug 2019 08:18:21 GMT-07:00

Equivalent Doses Matter, Rather Than Types

Hanafusa, Norio — Fri, 16 Aug 2019 05:39:05 GMT-07:00

GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Meta-Analysis of Treatment Effects of Randomized Controlled Trials

Inker, Lesley A. — Wed, 10 Jul 2019 06:16:04 GMT-07:00

Performance of GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Statistical Simulation

Greene, Tom — Wed, 10 Jul 2019 06:16:05 GMT-07:00

Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data

Grams, Morgan E. — Wed, 10 Jul 2019 06:16:05 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 30 Aug 2019 10:00:28 GMT-07:00

Twist1 in Infiltrating Macrophages Attenuates Kidney Fibrosis via Matrix Metallopeptidase 13–Mediated Matrix Degradation

Ren, Jiafa — Wed, 17 Jul 2019 07:58:21 GMT-07:00

Trends and Racial Disparities of Palliative Care Use among Hospitalized Patients with ESKD on Dialysis

Wen, Yumeng — Tue, 06 Aug 2019 08:18:22 GMT-07:00

A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia

Fishbane, Steven — Fri, 14 Jun 2019 03:30:07 GMT-07:00

Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis

Clayton, Philip A. — Mon, 15 Jul 2019 04:33:33 GMT-07:00

Referral for Kidney Transplantation in Canadian Provinces

Kim, S. Joseph — Tue, 06 Aug 2019 08:18:21 GMT-07:00

Variation in Kidney Transplant Referral: How Much More Evidence Do We Need To Justify Data Collection on Early Transplant Steps?

Patzer, Rachel E. — Tue, 06 Aug 2019 08:18:21 GMT-07:00

The Effect of Medicaid Expansion on Self-Reported Kidney Disease

Tummalapalli, Sri Lekha — Thu, 16 May 2019 08:47:54 GMT-07:00

Correction

American Society of Nephrology — Wed, 22 May 2019 08:23:43 GMT-07:00

Bariatric Surgery for ESKD Patients

Erickson, Kevin F. — Thu, 25 Jul 2019 08:53:03 GMT-07:00

Does Epitope Spreading Influence Responsiveness to Rituximab in PLA2R-Associated Membranous Nephropathy?

Salant, David J. — Wed, 24 Jul 2019 06:56:00 GMT-07:00

An ADPKD Patient’s View on Screening for Intracranial Aneurysms

Fowler, Kevin John — Tue, 30 Jul 2019 07:23:20 GMT-07:00

Intracranial Aneurysms in ADPKD

Kuo, Ivana Y. — Tue, 30 Jul 2019 07:23:21 GMT-07:00

Expanded Prospective Payment System and Use of and Outcomes with Home Dialysis by Race and Ethnicity in the United States

Shen, Jenny I. — Thu, 18 Jul 2019 10:17:53 GMT-07:00

Prediction of Risk of Death for Patients Starting Dialysis

Anderson, Ryan T. — Tue, 30 Jul 2019 07:23:21 GMT-07:00

Presymptomatic Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease

Sanchis, Irina M. — Tue, 30 Jul 2019 07:23:21 GMT-07:00

Trends in Bariatric Surgery Procedures among Patients with ESKD in the United States

Sheetz, Kyle H. — Thu, 25 Jul 2019 08:53:02 GMT-07:00

Public Policy and Equal Access to Home Dialysis

Cavanaugh, Kerri L. — Thu, 18 Jul 2019 10:17:53 GMT-07:00

Clinical Pharmacology in Diuretic Use

Ellison, David H. — Mon, 01 Apr 2019 06:46:34 GMT-07:00

Managing Kidney Failure with Home Hemodialysis

Ibrahim, Ali — Wed, 24 Jul 2019 06:55:59 GMT-07:00

There is a resurgence in clinical adoption of home hemodialysis globally driven by several demonstrated clinical and economic advantages. Yet, the overall adoption of home hemodialysis remains under-represented in most countries. The practicality of managing ESKD with home hemodialysis is a common concern among practicing nephrologists in the United States. The primary objective of this invited feature is to deliver a practical guide to managing ESKD with home hemodialysis. We have included common clinical scenarios, clinical and infrastructure management problems, and approaches to the day-to-day management of patients undergoing home hemodialysis.

Trends in Quality of Care for Patients with CKD in the United States

Tummalapalli, Sri Lekha — Thu, 11 Jul 2019 06:35:15 GMT-07:00

Urinary Melamine Levels and Progression of CKD

Tsai, Yi-Chun — Tue, 23 Jul 2019 07:31:11 GMT-07:00

The Status of Provision of Standard Outpatient Dialysis for US Undocumented Immigrants with ESKD

Cervantes, Lilia — Thu, 06 Jun 2019 07:47:28 GMT-07:00

Performance Measurement and the Kidney Quality Improvement Registry

Fischer, Michael J. — Mon, 10 Jun 2019 07:37:58 GMT-07:00

IDEAL-ICU in Context

Leaf, David E. — Wed, 17 Jul 2019 07:59:38 GMT-07:00

Efficacy and Safety of Esaxerenone (CS-3150) for the Treatment of Type 2 Diabetes with Microalbuminuria

Ito, Sadayoshi — Thu, 27 Jun 2019 06:22:24 GMT-07:00

Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease

Flahault, Adrien — Wed, 19 Jun 2019 07:43:31 GMT-07:00

Metabolic Acidosis in a Patient with CKD

Qian, Qi — Wed, 24 Apr 2019 07:21:41 GMT-07:00

Access to Kidney Transplantation after a Failed First Kidney Transplant and Associations with Patient and Allograft Survival

Clark, Stephanie — Tue, 23 Jul 2019 07:31:11 GMT-07:00

Patient-Centered Outcomes with Second Kidney Transplant

Mohan, Sumit — Tue, 23 Jul 2019 07:31:12 GMT-07:00

High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy

Seitz-Polski, Barbara — Wed, 24 Jul 2019 06:56:00 GMT-07:00

IgA Nephropathy in Elderly Patients

Sevillano, Angel M. — Tue, 16 Jul 2019 09:23:20 GMT-07:00

Authors’ Reply

Chu, Nadia M. — Fri, 12 Jul 2019 07:10:03 GMT-07:00

The Complex Role of Interleukin 6 in Regulating T-cell Responses during Acute Glomerulonephritis

Cormican, Sarah — Tue, 16 Jul 2019 09:26:50 GMT-07:00

Time’s Up! Start Dialysis Later in Children

Larkins, Nicholas G. — Thu, 18 Jul 2019 10:18:05 GMT-07:00

Erratum

American Society of Nephrology — Wed, 31 Jul 2019 10:00:29 GMT-07:00

This Month's Highlights

American Society of Nephrology — Wed, 31 Jul 2019 10:00:29 GMT-07:00

A Novel Role for IL-6 Receptor Classic Signaling: Induction of RORγt+Foxp3+ Tregs with Enhanced Suppressive Capacity

Hagenstein, Julia — Tue, 16 Jul 2019 09:26:51 GMT-07:00

Sprouty1 Controls Genitourinary Development via its N-Terminal Tyrosine

Vaquero, Marta — Fri, 12 Jul 2019 07:10:03 GMT-07:00

Apoptotic Cell–Induced, Antigen-Specific Immunoregulation to Treat Experimental Antimyeloperoxidase GN

Gan, Poh-Yi — Tue, 23 Jul 2019 07:31:24 GMT-07:00

Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter

Cheng, Lei — Fri, 28 Jun 2019 06:38:24 GMT-07:00

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT

Beddhu, Srinivasan — Fri, 19 Jul 2019 06:09:30 GMT-07:00

Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome

Dufek, Stephanie — Mon, 01 Jul 2019 09:03:45 GMT-07:00

Glomerular Volume and Glomerulosclerosis at Different Depths within the Human Kidney

Denic, Aleksandar — Fri, 05 Jul 2019 10:37:54 GMT-07:00

Erythrocyte Adenosine A2B Receptor-Mediated AMPK Activation: A Missing Component Counteracting CKD by Promoting Oxygen Delivery

Peng, Zhangzhe — Fri, 05 Jul 2019 10:37:55 GMT-07:00

A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD

Block, Geoffrey A. — Fri, 05 Jul 2019 10:37:54 GMT-07:00

Automatic Measurement of Kidney and Liver Volumes from MR Images of Patients Affected by Autosomal Dominant Polycystic Kidney Disease

van Gastel, Maatje D.A. — Wed, 03 Jul 2019 08:02:01 GMT-07:00

A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection

Zhang, Weijia — Fri, 05 Jul 2019 10:37:55 GMT-07:00

Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium during Increased Dietary Potassium Intake

Wu, Peng — Tue, 25 Jun 2019 08:40:48 GMT-07:00

Higher eGFR at Dialysis Initiation Is Not Associated with a Survival Benefit in Children

Winnicki, Erica — Thu, 18 Jul 2019 10:18:05 GMT-07:00

Enemy Action in the Distal Convoluted Tubule

Ellison, David H. — Mon, 08 Jul 2019 07:36:16 GMT-07:00

Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Escherichia coli Infection

Eichler, Tad — Tue, 25 Jun 2019 08:40:47 GMT-07:00

Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study

Blanchard, Anne — Mon, 08 Jul 2019 07:36:17 GMT-07:00

Removing Disincentives to Kidney Donation: A Quantitative Analysis

McCormick, Frank — Thu, 25 Jul 2019 05:11:58 GMT-07:00

Cognitive Impairment after Kidney Transplant: a Hidden Consequence of Depression?

Moulton, Calum D. — Fri, 12 Jul 2019 07:10:03 GMT-07:00

Renal-Tubule Epithelial Cell Nomenclature for Single-Cell RNA-Sequencing Studies

Chen, Lihe — Fri, 28 Jun 2019 06:38:24 GMT-07:00

Fatal Attraction: Immunoglobulin A and the Glomerular Mesangium

Floege, Jürgen — Fri, 21 Jun 2019 06:33:20 GMT-07:00

Authors’ Reply

Wang, Virginia — Thu, 16 May 2019 08:48:44 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 28 Jun 2019 10:00:27 GMT-07:00

MAIT Cells as Drivers of Renal Fibrosis and CKD

Sawitzki, Birgit — Tue, 11 Jun 2019 07:46:34 GMT-07:00

Mesangial Deposition Can Strongly Involve Innate-Like IgA Molecules Lacking Affinity Maturation

Wehbi, Batoul — Fri, 21 Jun 2019 06:33:19 GMT-07:00

Human Tissue-Resident Mucosal-Associated Invariant T (MAIT) Cells in Renal Fibrosis and CKD

Law, Becker M. P. — Tue, 11 Jun 2019 07:46:34 GMT-07:00

Tyrosine Phosphorylation of CD2AP Affects Stability of the Slit Diaphragm Complex

Tossidou, Irini — Mon, 24 Jun 2019 05:02:30 GMT-07:00

Confounding of Race/Ethnicity and Age in the Survival among Veterans Obtaining Dialysis in VA and Non-VA Settings

Yan, Guofen — Thu, 16 May 2019 08:48:43 GMT-07:00

Bif-1 Interacts with Prohibitin-2 to Regulate Mitochondrial Inner Membrane during Cell Stress and Apoptosis

Cho, Sung-Gyu — Fri, 24 May 2019 08:25:14 GMT-07:00

The Case for Selective Withdrawal of Antidepressants in Patients with Advanced Kidney Disease

Chilcot, Joseph — Mon, 03 Jun 2019 08:25:07 GMT-07:00

Authors’ Reply

Assimon, Magdalene M. — Mon, 03 Jun 2019 08:25:08 GMT-07:00

Von Hippel-Lindau Acts as a Metabolic Switch Controlling Nephron Progenitor Differentiation

Cargill, Kasey — Wed, 29 May 2019 05:06:47 GMT-07:00

Safety of a Restrictive versus Liberal Approach to Red Blood Cell Transfusion on the Outcome of AKI in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial

Garg, Amit X. — Thu, 20 Jun 2019 06:00:03 GMT-07:00

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats

Krieger, Nancy S. — Fri, 17 May 2019 06:28:09 GMT-07:00

Trends in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use among Those with Impaired Kidney Function in the United States

Murphy, Daniel P. — Wed, 05 Jun 2019 05:17:49 GMT-07:00

Impact of AKI on Urinary Protein Excretion: Analysis of Two Prospective Cohorts

Hsu, Chi-yuan — Mon, 24 Jun 2019 05:02:30 GMT-07:00

Soluble Urokinase Plasminogen Activator Receptor and Decline in Kidney Function in Autosomal Dominant Polycystic Kidney Disease

Hayek, Salim S. — Thu, 06 Jun 2019 07:48:43 GMT-07:00

Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors: A Prospective Cohort Study

D’Costa, Matthew R. — Fri, 07 Jun 2019 08:41:24 GMT-07:00

The Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease (PSP-CKD) Study: A Cluster Randomized Trial in Primary Care

Major, Rupert W. — Thu, 16 May 2019 08:48:44 GMT-07:00

Restricting Red-Cell Transfusions in Cardiac Surgery: No Increase in AKI

Macdougall, Iain C. — Thu, 20 Jun 2019 06:00:03 GMT-07:00

Targeting Fall Risk in CKD

Kutner, Nancy G. — Mon, 24 Jun 2019 08:41:22 GMT-07:00

ESKD Risk in Living Kidney Donors “Like Me”

Newell, Kenneth A. — Tue, 25 Jun 2019 08:40:30 GMT-07:00

Statement of Clarification: Drug Coated Balloon Angioplasty in Failing AV Fistulas

American Society of Nephrology — Thu, 13 Jun 2019 07:54:28 GMT-07:00

Functioning on Dialysis

Abel, Daniel L. — Thu, 27 Jun 2019 06:22:24 GMT-07:00

Expression of Concern: Circulating Anti-endothelial Cell Antibodies Are Associated with Poor Outcome in Renal Allograft Recipients with Acute Rejection

American Society of Nephrology — Tue, 04 Jun 2019 08:58:09 GMT-07:00

Risk of ESKD in Older Live Kidney Donors with Hypertension

Al Ammary, Fawaz — Tue, 25 Jun 2019 08:40:31 GMT-07:00

Derivation and Validation of a Novel Risk Score to Predict Overcorrection of Severe Hyponatremia

Woodfine, Jason D. — Wed, 12 Jun 2019 05:58:36 GMT-07:00

Blood Pressure and Incident Atrial Fibrillation in Older Patients Initiating Hemodialysis

Chang, Tara I-Hsin — Fri, 07 Jun 2019 08:33:53 GMT-07:00

Treatment of Relapses in ANCA-Associated Vasculitis

McClure, Mark — Fri, 28 Jun 2019 05:10:22 GMT-07:00

Attitudes toward Peritoneal Dialysis among Peritoneal Dialysis and Hemodialysis Medical Directors

Shen, Jenny I. — Fri, 05 Jul 2019 10:00:22 GMT-07:00

Association of Initiation of Maintenance Dialysis with Functional Status and Caregiver Burden

Goto, Namiko A. — Thu, 27 Jun 2019 06:22:24 GMT-07:00

Clinical Pharmacology of Antibiotics

Eyler, Rachel F. — Tue, 12 Mar 2019 06:22:29 GMT-07:00

Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient’s individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug’s pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (e.g., β-lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (e.g., aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.

Association of CKD with Incident Tuberculosis

Park, Sehoon — Thu, 06 Jun 2019 07:47:28 GMT-07:00

Gait Abnormalities and the Risk of Falls in CKD

Tran, Jeannie — Mon, 24 Jun 2019 08:41:23 GMT-07:00

Use of a Medical-Alert Accessory in CKD

Farhy, Eli — Thu, 06 Jun 2019 07:47:29 GMT-07:00

Effects of Treatment of Metabolic Acidosis in CKD

Navaneethan, Sankar D. — Thu, 13 Jun 2019 07:54:29 GMT-07:00

AKI Associated with Acute Pancreatitis

Nassar, Tareq I. — Wed, 22 May 2019 08:23:43 GMT-07:00

Acute pancreatitis is a common disorder of the pancreas. It is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Its severity ranges from mild self-limited disease to severe acute necrotizing pancreatitis characterized by systemic complications and multiorgan failure. Severe acute pancreatitis develops in about 20% of patients with acute pancreatitis and may be associated with multiorgan failure (respiratory, cardiovascular, and kidney). AKI is a frequent complication of severe acute pancreatitis and develops late in the course of the disease, usually after the failure of other organs. It carries a very poor prognosis, particularly if kidney replacement therapy is required, with mortality rates exceeding 75%. The exact pathophysiology of AKI in acute pancreatitis remains unclear but appears to result from initial volume depletion followed by complex vascular and humoral factors. Here, we provide an overview of the epidemiology, pathogenesis, causes, and management of AKI in patients with severe acute pancreatitis.

Peritoneal Dialysis–Associated Peritonitis

Szeto, Cheuk-Chun — Wed, 08 May 2019 06:45:56 GMT-07:00

Peritonitis is a common and severe complication in peritoneal dialysis (PD). Detailed recommendations on the prevention and treatment of PD-associated peritonitis have been published by the International Society for Peritoneal Dialysis (ISPD), but there is a substantial variation in clinical practice among dialysis units. Prophylactic antibiotics administered before PD catheter insertion, colonoscopy, or invasive gynecologic procedures, daily topical application of antibiotic cream or ointment to the catheter exit site, and prompt treatment of exit site or catheter infection are key measures to prevent PD-associated peritonitis. When a patient on PD presents with clinical features compatible with PD-associated peritonitis, empirical antibiotic therapy, with coverage of both Gram-positive and Gram-negative organisms (including Pseudomonas species), should be started once the appropriate microbiologic specimens have been obtained. Intraperitoneal is the preferred route of administration. Antifungal prophylaxis, preferably oral nystatin, should be added to prevent secondary fungal peritonitis. Once the PD effluent Gram stain or culture and sensitivity results are available, antibiotic therapy can be adjusted accordingly. A detailed description on the dosage of individual antibiotic can be found in the latest recommendations by the ISPD. The duration of antibiotics is usually 2–3 weeks, depending on the specific organisms identified. Catheter removal and temporary hemodialysis support is recommended for refractory, relapsing, or fungal peritonitis. In some patients, a new PD catheter could be inserted after complete resolution of the peritonitis. PD catheter removal should also be considered for refractory exit site or tunnel infections. After the improvement in clinical practice, there is a worldwide trend of reduction in PD-associated peritonitis rate, supporting the use of PD as a first-line dialysis modality.

Mycophenolate Mofetil Versus Cyclophosphamide for the Induction of Remission in Nonlife-Threatening Relapses of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Tuin, Janneke — Fri, 28 Jun 2019 05:10:23 GMT-07:00

Advancing Equity in Nephrology

Mohottige, Dinushika — Wed, 22 May 2019 08:23:43 GMT-07:00

Burosumab Therapy for X-Linked Hypophosphatemia and Therapeutic Implications for CKD

Perwad, Farzana — Thu, 06 Jun 2019 07:47:27 GMT-07:00

Geriatric Assessment in Advanced Kidney Disease

Brown, Edwina Anne — Wed, 22 May 2019 08:23:44 GMT-07:00

AKI in Patients Receiving Immune Checkpoint Inhibitors

Perazella, Mark A. — Thu, 02 May 2019 10:52:51 GMT-07:00

The Hypertensive Adolescent

Flynn, Joseph T. — Wed, 24 Apr 2019 07:21:41 GMT-07:00

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation

Ziemann, Malte — Tue, 18 Jun 2019 06:12:23 GMT-07:00

Expression of Concern: Re-Establishing Brain Networks in Patients with ESRD after Successful Kidney Transplantation

American Society of Nephrology — Wed, 24 Apr 2019 07:21:39 GMT-07:00

Clinical and Public Policy Implications of Pre-Formed DSA and Transplant Outcomes

Huang, Edmund — Tue, 18 Jun 2019 06:12:23 GMT-07:00

Mitochondria in Sepsis-Induced AKI

Sun, Jian — Fri, 10 May 2019 06:03:23 GMT-07:00

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%–80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.

Compromising Outcomes

Imrey, Peter B. — Mon, 17 Jun 2019 05:01:56 GMT-07:00

Osmoregulation Performance and Kidney Transplant Outcome

Mazloum, Manal — Wed, 19 Jun 2019 07:57:40 GMT-07:00

A “Set Point” for Water Homeostasis Disturbed with Altered Kidney Transplantation Outcome

Bichet, Daniel G. — Wed, 19 Jun 2019 07:57:40 GMT-07:00

Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use

Kwun, Jean — Fri, 21 Jun 2019 06:33:21 GMT-07:00

Deceased Donor Kidneys Are Harder to Place on the Weekend

King, Kristen L. — Tue, 23 Apr 2019 08:39:18 GMT-07:00

Correction

American Society of Nephrology — Wed, 15 May 2019 06:17:59 GMT-07:00

Correction

American Society of Nephrology — Wed, 15 May 2019 06:17:58 GMT-07:00

Correction

American Society of Nephrology — Wed, 15 May 2019 06:17:58 GMT-07:00

Correction

American Society of Nephrology — Wed, 15 May 2019 06:17:58 GMT-07:00

A Combination of Change in Albuminuria and GFR as a Surrogate End Point for Progression of CKD

Coresh, Josef — Mon, 03 Jun 2019 08:23:17 GMT-07:00

Postdialysis Hypokalemia and All-Cause Mortality in Patients Undergoing Maintenance Hemodialysis

Ohnishi, Tsuyoshi — Thu, 02 May 2019 10:52:51 GMT-07:00

Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes

Ohkuma, Toshiaki — Mon, 03 Jun 2019 08:23:18 GMT-07:00

Quality Improvement Goals for Acute Kidney Injury

Kashani, Kianoush — Fri, 17 May 2019 06:27:52 GMT-07:00

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators.

Hyperfiltration

Tummalapalli, Sri Lekha — Thu, 23 May 2019 08:24:31 GMT-07:00

Managing Fluid Control in the Peritoneal Dialysis Population

Gilford, Shari — Thu, 23 May 2019 08:24:32 GMT-07:00

Therapeutic Potential of Newer Drugs for Treating Hyperkalemia

Weir, Matthew R. — Mon, 20 May 2019 06:37:19 GMT-07:00

CJASN and Disclosure of Conflicts of Interest

Mehrotra, Rajnish — Wed, 15 May 2019 06:17:58 GMT-07:00

Growth Pattern of Kidney Cyst Number and Volume in Autosomal Dominant Polycystic Kidney Disease

Bae, Kyongtae T. — Tue, 14 May 2019 05:21:59 GMT-07:00

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia

Spinowitz, Bruce S. — Mon, 20 May 2019 06:37:18 GMT-07:00

Proteomic Analysis of Urinary Microvesicles and Exosomes in Medullary Sponge Kidney Disease and Autosomal Dominant Polycystic Kidney Disease

Bruschi, Maurizio — Wed, 24 Apr 2019 07:21:40 GMT-07:00

Clinical Pharmacology Considerations in Pain Management in Patients with Advanced Kidney Failure

Davison, Sara N. — Mon, 04 Mar 2019 07:09:57 GMT-08:00

Pain is common and poorly managed in patients with advanced CKD, likely due to both under and over prescription of appropriate analgesics. Poorly managed pain contributes to patients’ poor quality of life and excessive health care use. There is tremendous variability within and between countries in prescribing patterns of analgesics, suggesting that factors other than patient characteristics account for these differences. This article discusses the pharmacologic management of acute and chronic pain in patients with advanced CKD, and the role analgesics, including opioids, play in the overall approach to pain management.

Evolution Over Time of Volume Status and PD-Related Practice Patterns in an Incident Peritoneal Dialysis Cohort

Van Biesen, Wim — Thu, 23 May 2019 08:24:31 GMT-07:00

Hypoglycemia in People with Type 2 Diabetes and CKD

Ahmad, Iram — Wed, 17 Apr 2019 05:03:09 GMT-07:00

Early Glomerular Hyperfiltration and Long-Term Kidney Outcomes in Type 1 Diabetes

Molitch, Mark E. — Thu, 23 May 2019 08:24:32 GMT-07:00

IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD

Hung, Adriana M. — Tue, 23 Apr 2019 08:39:19 GMT-07:00

A Nutritional Lie or Lifestyle?

Gee, Patrick O. — Thu, 25 Apr 2019 08:06:53 GMT-07:00

Serum Metabolites and Cardiac Death in Patients on Hemodialysis

Hu, Jiun-Ruey — Mon, 08 Apr 2019 05:21:09 GMT-07:00

Correction

American Society of Nephrology — Fri, 22 Mar 2019 06:46:37 GMT-07:00

Blood Microbiome in CKD

Mair, Robert D. — Mon, 08 Apr 2019 05:21:09 GMT-07:00

Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure

Charokopos, Antonios — Mon, 22 Apr 2019 04:37:36 GMT-07:00

Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients

Chauhan, Kinsuk — Thu, 04 Apr 2019 08:01:02 GMT-07:00

Diagnostic Performance of Blood Pressure Measurement Modalities in Living Kidney Donor Candidates

Armanyous, Sherif — Thu, 04 Apr 2019 08:01:01 GMT-07:00

Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients

Li, Xiaojuan — Mon, 15 Apr 2019 07:52:05 GMT-07:00

Treatment Options for Refractory Lupus Nephritis

Anders, Hans-Joachim — Fri, 12 Apr 2019 05:26:18 GMT-07:00

Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKD

Sinha, Arjun D. — Tue, 13 Nov 2018 05:46:38 GMT-08:00

CKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting α-agonists. Recent evidence suggests that β-adrenergic blocking agents may have a greater role in patients on dialysis and that thiazide diuretics may have a greater role in patients with advanced CKD. We conclude with sharing our general prescribing algorithm for both patients with predialysis CKD and patients with ESKD on dialysis.

Mechanistic Insights into Loop Diuretic Responsiveness in Heart Failure

Ellison, David H. — Mon, 22 Apr 2019 04:37:35 GMT-07:00

Evidence for Managing Hypernatremia

Sterns, Richard H. — Thu, 04 Apr 2019 08:01:01 GMT-07:00

Vascular Access for Hemodialysis Patients

Allon, Michael — Thu, 11 Apr 2019 05:03:23 GMT-07:00

This commentary critically examines key assumptions and recommendations in the 2006 Kidney Disease Outcomes Quality Initiative vascular access guidelines, and argues that several are not relevant to the contemporary United States hemodialysis population. First, the guidelines prefer arteriovenous fistulas (AVFs) over arteriovenous grafts (AVGs), on the basis of their superior secondary survival and lower frequency of interventions and infections. However, intent-to-treat analyses that incorporate the higher primary failure of AVFs, demonstrate equivalent secondary survival of both access types. Moreover, the lower rate of AVF versus AVG infections is counterbalanced by the higher rate of catheter-related bloodstream infections before AVF maturation. In addition, AVFs with assisted maturation (interventions before successful AVF use), which account for about 50% of new AVFs, are associated with inferior secondary patency compared with AVGs without intervention before successful use. Second, the guidelines posit lower access management costs for AVFs than AVGs. However, in patients who undergo AVF or AVG placement after starting dialysis with a central venous catheter (CVC), the overall cost of access management is actually higher in patients receiving an AVF. Third, the guidelines prefer forearm over upper arm AVFs. However, published data demonstrate superior maturation of upper arm versus forearm AVFs, likely explaining the progressive increase in upper arm AVFs in the United States. Fourth, AVFs are thought to fail primarily because of aggressive juxta-anastomotic stenosis. However, recent evidence suggests that many AVFs mature despite neointimal hyperplasia, and that suboptimal arterial vasodilation may be an equally important contributor to AVF nonmaturation. Finally, CVC use is believed to result in excess mortality in patients on hemodialysis. However, recent data suggest that CVC use is simply a surrogate marker of sicker patients who are more likely to die, rather than being a mediator of mortality.

Duration of Dual Antiplatelet Therapy in Patients with CKD and Drug-Eluting Stents

Mavrakanas, Thomas A. — Mon, 22 Apr 2019 04:37:35 GMT-07:00

Anticoagulant-Related Nephropathy

Glassock, Richard J. — Tue, 21 May 2019 07:29:07 GMT-07:00

Place of Percutaneous Fistula Devices in Contemporary Management of Vascular Access

Wasse, Haimanot — Mon, 01 Apr 2019 06:46:34 GMT-07:00

Vitamin D and Cardiovascular Complications of CKD

Banerjee, Debasish — Tue, 07 May 2019 04:07:29 GMT-07:00

The Bone after Kidney Transplantation

Drüeke, Tilman B. — Tue, 14 May 2019 05:22:00 GMT-07:00

Changes in Bone Histomorphometry after Kidney Transplantation

Keronen, Satu — Tue, 14 May 2019 05:22:00 GMT-07:00

Management of Adult Minimal Change Disease

Korbet, Stephen M. — Fri, 05 Apr 2019 06:39:38 GMT-07:00

Cerebral Ischemia and Cognitive Dysfunction in Patients on Dialysis

Moist, Louise M. — Mon, 22 Apr 2019 04:37:36 GMT-07:00

Nephrin Signaling Results in Integrin β1 Activation

Dlugos, Christopher Philipp — Thu, 16 May 2019 08:48:43 GMT-07:00

Exostosin 1/Exostosin 2–Associated Membranous Nephropathy

Sethi, Sanjeev — Mon, 06 May 2019 05:56:59 GMT-07:00

A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD

Sakaguchi, Yusuke — Mon, 29 Apr 2019 09:08:26 GMT-07:00

Erythropoiesis-Stimulating Agents and Mortality

Drüeke, Tilman B. — Tue, 23 Apr 2019 08:44:18 GMT-07:00

Authors’ Reply

Pun, Patrick H. — Mon, 06 May 2019 05:56:59 GMT-07:00

CPR for OHCA Is Rarely Successful, and What Is “Success” Anyway?

Gelfand, Samantha L. — Mon, 06 May 2019 05:56:59 GMT-07:00

Podocyte-Specific Sialylation-Deficient Mice Serve as a Model for Human FSGS

Niculovic, Kristina M. — Tue, 30 Apr 2019 09:11:00 GMT-07:00

Exome-Based Rare-Variant Analyses in CKD

Cameron-Christie, Sophia — Mon, 13 May 2019 07:09:19 GMT-07:00

Dual Inhibition of Gastrointestinal Phosphate Absorption: More Questions Than Answers

Yeung, Wing-Chi G. — Mon, 13 May 2019 07:09:20 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 31 May 2019 10:00:29 GMT-07:00

One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study)

Wong, Germaine — Tue, 30 Apr 2019 09:11:01 GMT-07:00

Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells

Giesecke, Torsten — Thu, 16 May 2019 08:48:44 GMT-07:00

Matching Human Unilateral AKI, a Reverse Translational Approach to Investigate Kidney Recovery after Ischemia

Soranno, Danielle E. — Thu, 09 May 2019 07:00:23 GMT-07:00

Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial

Ix, Joachim H. — Mon, 13 May 2019 07:09:20 GMT-07:00

Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null Mice

Salerno, Emily E. — Tue, 30 Apr 2019 09:10:59 GMT-07:00

Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate Cooling

Marants, Raanan — Fri, 03 May 2019 06:45:00 GMT-07:00

Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis

Sakaguchi, Yusuke — Tue, 23 Apr 2019 08:44:17 GMT-07:00

Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes

Sakai, Shinsuke — Tue, 30 Apr 2019 09:11:01 GMT-07:00

Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 Diabetes

Looker, Helen C. — Fri, 31 May 2019 10:00:30 GMT-07:00

Protein O-GlcNAcylation Is Essential for the Maintenance of Renal Energy Homeostasis and Function via Lipolysis during Fasting and Diabetes

Sugahara, Sho — Wed, 01 May 2019 12:15:13 GMT-07:00

Arterial Stiffness in the Heart Disease of CKD

Zanoli, Luca — Tue, 30 Apr 2019 09:11:00 GMT-07:00

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.

Pyelonephritis: A Historical Reappraisal

Anumudu, Samaya — Fri, 26 Apr 2019 06:42:40 GMT-07:00

Solving Baroreceptor Mystery: Role of PIEZO Ion Channels

Burke, Suzanne D. — Wed, 01 May 2019 12:15:12 GMT-07:00

Blood Microbiome Profile in CKD

Shah, Neal B. — Mon, 08 Apr 2019 05:21:09 GMT-07:00

Pruritus and Patient Reported Outcomes in Non-Dialysis CKD

Sukul, Nidhi — Thu, 11 Apr 2019 05:03:23 GMT-07:00

Plant-Based Diets and Incident CKD and Kidney Function

Kim, Hyunju — Thu, 25 Apr 2019 08:06:53 GMT-07:00

Hepatorenal Syndrome

Francoz, Claire — Wed, 17 Apr 2019 05:03:07 GMT-07:00

Hepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver–kidney transplantation.

Major Adverse Kidney Events in Pediatric Sepsis

Weiss, Scott L. — Thu, 18 Apr 2019 06:41:38 GMT-07:00

How Community Engagement Is Enhancing NIDDK Research

Kimmel, Paul L. — Wed, 27 Mar 2019 07:03:06 GMT-07:00

Transitional Care Units: Greater Than the Sum of Their Parts

Bowman, Brendan T. — Wed, 27 Mar 2019 07:03:06 GMT-07:00

Retooling Nephrology with Ultrasound

O’Neill, W. Charles — Wed, 27 Mar 2019 07:03:06 GMT-07:00

Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

Huang, Xianghua — Fri, 12 Apr 2019 05:26:17 GMT-07:00

Post-Transplant Lymphoproliferative Disorder in a Kidney Transplant Recipient

Agarwal, Gaurav — Mon, 25 Feb 2019 09:10:54 GMT-08:00

A Case of ANCA-Associated Vasculitis

Hogan, Jonathan J. — Fri, 05 Apr 2019 06:39:37 GMT-07:00

Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital Imaging

Nakano, Daisuke — Wed, 08 Apr 2015 01:17:09 GMT-07:00

Urine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4–dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation.

Cellular Senescence in the Kidney

Docherty, Marie-Helena — Thu, 18 Apr 2019 07:55:21 GMT-07:00

Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease—implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.

This Month's Highlights

American Society of Nephrology — Tue, 30 Apr 2019 10:00:25 GMT-07:00

Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance

Opdebeeck, Britt — Tue, 02 Apr 2019 06:59:55 GMT-07:00

Protein Phosphatase 1 Inhibitor–1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl Cotransporter

Penton, David — Fri, 22 Mar 2019 06:46:48 GMT-07:00

Thrombospondin Type 1 Domain–Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated Podocytes

Herwig, Johanna — Wed, 10 Apr 2019 08:09:50 GMT-07:00

Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic Syndrome

Zhao, Feng — Mon, 25 Mar 2019 04:21:47 GMT-07:00

Filling the Gap: Drosophila Nephrocytes as Model System in Kidney Research

Marelja, Zvonimir — Mon, 25 Mar 2019 04:21:46 GMT-07:00

Severe Arterial Hypertension from Cullin 3 Mutations Is Caused by Both Renal and Vascular Effects

Abdel Khalek, Waed — Tue, 09 Apr 2019 04:37:58 GMT-07:00

An Antifungal for Antidiuresis?

Verbalis, Joseph G. — Fri, 12 Apr 2019 05:27:19 GMT-07:00

Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study

Jarrick, Simon — Wed, 10 Apr 2019 08:09:50 GMT-07:00

Authors’ Reply

Marques, Igor Denizarde Bacelar — Mon, 25 Mar 2019 04:21:48 GMT-07:00

Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking

Vukićević, Tanja — Mon, 15 Apr 2019 07:52:24 GMT-07:00

Mortality Risk in IgA Nephropathy

Glassock, Richard J. — Wed, 10 Apr 2019 08:09:50 GMT-07:00

Single-Cell RNA Sequencing Identifies Candidate Renal Resident Macrophage Gene Expression Signatures across Species

Zimmerman, Kurt A. — Thu, 04 Apr 2019 08:01:11 GMT-07:00

GNAS: A New Nephrogenic Cause of Inappropriate Antidiuresis

Bichet, Daniel G. — Mon, 08 Apr 2019 05:32:29 GMT-07:00

Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population

Tanikawa, Chizu — Thu, 11 Apr 2019 05:08:13 GMT-07:00

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration

Dember, Laura M. — Thu, 18 Apr 2019 07:55:21 GMT-07:00

Germline-Derived Gain-of-Function Variants of Gsα-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis

Miyado, Mami — Mon, 08 Apr 2019 05:32:29 GMT-07:00

Inhibition of Sodium Glucose Cotransporter 2 Attenuates the Dysregulation of Kelch-Like 3 and NaCl Cotransporter in Obese Diabetic Mice

Ishizawa, Kenichi — Tue, 26 Mar 2019 06:34:53 GMT-07:00

How to Find a Resident Kidney Macrophage: the Single-Cell Sequencing Solution

Clatworthy, Menna R. — Thu, 04 Apr 2019 08:01:11 GMT-07:00

Biphosphonate Therapy, Risk of Fracture, and Sites of Bone Mineral Density Assessments in Kidney Transplantation

Tabibzadeh, Nahid — Mon, 25 Mar 2019 04:21:47 GMT-07:00

T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy

Winterberg, Pamela D. — Wed, 06 Feb 2019 07:08:20 GMT-08:00

Iron, Hepcidin, and Death in Human AKI

Leaf, David E. — Fri, 08 Feb 2019 05:19:07 GMT-08:00

Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting Ducts

Ishikawa, Yasunobu — Mon, 11 Feb 2019 03:41:49 GMT-08:00

Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Coq6 Knockout Mice

Widmeier, Eugen — Fri, 08 Feb 2019 05:19:07 GMT-08:00

Long-Range Chromatin Interactions in the Kidney

Guan, Yuting — Wed, 13 Feb 2019 06:28:49 GMT-08:00

Cardiopulmonary Resuscitation in Outpatient Dialysis Clinics: Perception of Futility?

Imbeault, Benoit — Thu, 07 Feb 2019 06:03:22 GMT-08:00

Erratum

American Society of Nephrology — Thu, 28 Feb 2019 10:00:23 GMT-08:00

Erratum

American Society of Nephrology — Thu, 28 Feb 2019 10:00:23 GMT-08:00

Erratum

American Society of Nephrology — Thu, 28 Feb 2019 10:00:23 GMT-08:00

An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized Trial

Selby, Nicholas M. — Thu, 21 Feb 2019 12:58:52 GMT-08:00

A Pragmatic Step Forward: AKI and Beyond

Dember, Laura M. — Thu, 21 Feb 2019 12:58:52 GMT-08:00

Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci

Sieber, Karsten B. — Wed, 13 Feb 2019 06:28:49 GMT-08:00

Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis

Khamaysi, Ahlam — Wed, 06 Feb 2019 07:08:21 GMT-08:00

Lower Extremity Amputation and Health Care Utilization in the Last Year of Life among Medicare Beneficiaries with ESRD

Butler, Catherine R. — Tue, 19 Feb 2019 06:47:10 GMT-08:00

Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis Clinics

Pun, Patrick H. — Thu, 07 Feb 2019 06:03:21 GMT-08:00

This Month's Highlights

American Society of Nephrology — Thu, 28 Feb 2019 10:00:23 GMT-08:00

Traditional Urinary Biomarkers in the Assessment of Hospital-Acquired AKI

mark.perazella@yale.edu — Thu, 17 Nov 2011 08:23:00 GMT-08:00

Traditional biomarkers, such as urine chemistries and urine microscopic elements, are used in the diagnosis and care of patients with AKI. Urine chemistries, such as fractional excretion of sodium and fractional excretion of urea, are useful for differentiating prerenal AKI from acute tubular necrosis only in select patients. Urine microscopy using a quantitative evaluation of the urine sediment for renal tubular epithelial cells, renal tubular epithelial cell casts, and granular casts has recently been shown to differentiate prerenal AKI from acute tubular necrosis and also provide prognostic information. Urine microscopy has also been noted to compare favorably with new urine biomarkers for diagnosis and prognosis of AKI. Thus, current information on urine diagnostics suggests that urine chemistries have a limited role in differential diagnosis of AKI, whereas urine microscopy and new urine biomarkers may be used together to differentiate prerenal AKI from acute tubular necrosis and predict such outcomes as worsened AKI, acute dialysis, and death.

Recovery of Kidney Function in Children Treated with Maintenance Dialysis

Bonthuis, Marjolein — Thu, 20 Sep 2018 09:05:10 GMT-07:00

Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant Polycystic Kidney Disease

Nowak, Kristen L. — Tue, 18 Sep 2018 08:09:52 GMT-07:00

The Relationship between Intradialytic Hypotension and Hospitalized Mesenteric Ischemia

Seong, Eun Young — Thu, 20 Sep 2018 09:05:09 GMT-07:00

Inching toward a Greater Understanding of Genetic Hypercalciuria

Shah, Ronak Jagdeep — Wed, 19 Sep 2018 07:31:57 GMT-07:00

Proton Pump Inhibitors in Kidney Disease

Lazarus, Benjamin — Thu, 27 Sep 2018 07:58:47 GMT-07:00

Uromodulin and Nephron Mass

Pivin, Edward — Fri, 27 Jul 2018 09:42:09 GMT-07:00

Metabolic Acidosis and Cardiovascular Disease Risk in CKD

Abramowitz, Matthew K. — Thu, 20 Sep 2018 09:05:11 GMT-07:00

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

Stanifer, John W. — Thu, 13 Sep 2018 10:03:40 GMT-07:00

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis

Vangala, Chandan — Thu, 27 Sep 2018 07:58:48 GMT-07:00

Young Kidney Professionals’ Perspectives and Attitudes about Consuming Scientific Information

Tong, Allison — Fri, 24 Aug 2018 05:38:16 GMT-07:00

The digital era has seen rapid changes in how information is consumed. Traditional dissemination of scholarly work through biomedical journals may not be optimally tailored to the preferences of younger clinicians and researchers. We aimed to describe the perspectives of young clinicians and researchers in kidney disease on consuming scientific information. Three focus groups were conducted during the 2017 American Society of Nephrology Kidney Week with a total of 29 nephrologists and researchers (ages 40 years old and younger) purposively sampled through our networks and the American Society of Nephrology registration database. Data were analyzed thematically. Of the 72 participants invited, 29 participated from 28 centers across 13 countries. Five themes were identified: capturing and retaining attention (with subthemes of triggering interest, optimizing readability, and navigation to sustain motivation); having discernible relevance (resonating with clinical and research interests, supporting professional development, action-oriented and readily applicable, able to disseminate, contextualizing the study, and filtering out informational noise); immediacy and efficiency in processing information (requiring instantaneous and easy access, enabling rapid understanding, and facilitating comprehension of complex concepts); trusting legitimate and credible sources (authoritative indicator of importance and quality, reputable experts broadening perspective, certainty and confidence with collegial input, accurate framing and translation of the message, ascertaining methodologic detail and nuances, and integrating the patient perspective); and social dialoguing and debate. Immediate and digitally optimized access motivated young kidney professionals to consume scientific information. Mechanisms that enable them to distil relevant and new evidence, appraise and apply information to clinical practice and research, disseminate studies to colleagues, and engage in discussion and debate may enhance their comprehension, confidence, interpretation, and use of scientific literature.

PD Solutions and Peritoneal Health

Cho, Yeoungjee — Fri, 31 Aug 2018 06:55:10 GMT-07:00

Beware Intradialytic Hypotension

Inrig, Jula K. — Thu, 20 Sep 2018 09:05:10 GMT-07:00

Biocompatible Solutions and Long-Term Changes in Peritoneal Solute Transport

Elphick, Emma H. — Fri, 31 Aug 2018 06:55:11 GMT-07:00

Site of Care and Health Outcomes of Veterans Undergoing Maintenance Dialysis

Kourany, Wissam — Thu, 14 Jun 2018 06:51:37 GMT-07:00

The Changing Spectrum of Heroin-Associated Kidney Disease

Sethi, Sanjeev — Fri, 15 Jun 2018 07:25:42 GMT-07:00

Correction

American Society of Nephrology — Wed, 30 May 2018 07:37:14 GMT-07:00

Clinical Pharmacokinetics in Kidney Disease

Lea-Henry, Tom N. — Fri, 22 Jun 2018 06:19:46 GMT-07:00

Kidney disease is an increasingly common comorbidity that alters the pharmacokinetics of many drugs. Prescribing to patients with kidney disease requires knowledge about the drug, the extent of the patient’s altered physiology, and pharmacokinetic principles that influence the design of dosing regimens. There are multiple physiologic effects of impaired kidney function, and the extent to which they occur in an individual at any given time can be difficult to define. Although some guidelines are available for dosing in kidney disease, they may be on the basis of limited data or not widely applicable, and therefore, an understanding of pharmacokinetic principles and how to apply them is important to the practicing clinician. Whether kidney disease is acute or chronic, drug clearance decreases, and the volume of distribution may remain the same or increase. Although in CKD, these changes progress relatively slowly, they are dynamic in AKI, and recovery is possible depending on the etiology and treatments. This, and the use of kidney replacement therapies further complicate attempts to quantify drug clearance at the time of prescribing and dosing in AKI. The required change in the dosing regimen can be estimated or even quantitated in certain instances through the application of pharmacokinetic principles to guide rational drug dosing. This offers an opportunity to provide personalized medical care and minimizes adverse drug events from either under- or overdosing. We discuss the principles of pharmacokinetics that are fundamental for the design of an appropriate dosing regimen in this review.

Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis

Streja, Elani — Thu, 14 Jun 2018 06:51:36 GMT-07:00

12 Tips to Nephrology Teams Supporting Patients with Advanced Kidney Disease

Hickey, Edward V. — Thu, 28 Jun 2018 06:16:43 GMT-07:00

Overcoming Translational Barriers in Acute Kidney Injury

Zuk, Anna — Fri, 09 Mar 2018 06:45:09 GMT-08:00

AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “AKI Outcomes: Overcoming Barriers in AKI” workshop on February 10–12, 2015. The workshop used a reverse translational medicine approach to identify steps necessary to achieve clinical success. During the workshop, breakout groups were charged first to design feasible, phase 2, proof-of-concept clinical trials for delayed transplant graft function, prevention of AKI (primary prevention), and treatment of AKI (secondary prevention and recovery). Breakout groups then were responsible for identification of preclinical animal models that would replicate the pathophysiology of the phase 2 proof-of-concept patient population, including primary and secondary end points. Breakout groups identified considerable gaps in knowledge regarding human AKI, our understanding of the pathophysiology of AKI in preclinical animal models, and the fidelity of cellular and molecular targets that have been evaluated preclinically to provide information regarding human AKI of various etiologies. The workshop concluded with attendees defining a new path forward to a better understanding of the etiology, pathology, and pathophysiology of human AKI.

Urinary Phosphorus Excretion

Cupisti, Adamasco — Tue, 19 Jun 2018 08:09:53 GMT-07:00

Emotional Impact of Illness and Care on Patients with Advanced Kidney Disease

O’Hare, Ann M. — Thu, 28 Jun 2018 06:16:44 GMT-07:00

Evolving Epidemiology of Pediatric Glomerular Disease

Rheault, Michelle N. — Mon, 18 Jun 2018 08:20:51 GMT-07:00

Prevalence of Central Vein Stenosis in Patients Referred for Vein Mapping

Tedla, Fasika M. — Tue, 08 May 2018 08:04:08 GMT-07:00

Risk Factors and Outcomes of Rapid Correction of Severe Hyponatremia

George, Jason C. — Tue, 05 Jun 2018 06:50:04 GMT-07:00

Introduction to Nephropharmacology for the Clinician

Nolin, Thomas D. — Mon, 16 Apr 2018 07:17:07 GMT-07:00

Commentary on “Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in CKD”

Kestenbaum, Bryan R. — Fri, 28 Dec 2018 08:27:50 GMT-08:00

Correction

American Society of Nephrology — Mon, 19 Nov 2018 07:17:42 GMT-08:00

The Millennial Physician and the Obesity Epidemic

Kramer, Holly — Thu, 27 Dec 2018 07:36:17 GMT-08:00

Good Guys, Bad Guys, Guesses, and Near Misses in Nephrology

Edmonston, Daniel — Mon, 17 Dec 2018 07:27:02 GMT-08:00

Diet and Risk for Developing Kidney Disease

Sunwold, Duane — Thu, 27 Dec 2018 07:36:18 GMT-08:00

Patient Priorities for Research Involving Peritoneal Dialysis

Haydak, Jonathan — Thu, 20 Dec 2018 08:52:59 GMT-08:00

A Patient’s View on Exercise and ESKD

Jefferson, Nichole M. — Tue, 29 Jan 2019 08:36:56 GMT-08:00

Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis

Saglimbene, Valeria M. — Thu, 31 Jan 2019 09:00:36 GMT-08:00

Benefits and Barriers to and Desired Outcomes with Exercise in Patients with ESKD

Moorman, Danielle — Tue, 29 Jan 2019 08:36:57 GMT-08:00

Assessing Clinical Relevance of Uremic Toxins

Flythe, Jennifer E. — Mon, 21 Jan 2019 07:45:34 GMT-08:00

Correction

American Society of Nephrology — Thu, 10 Jan 2019 12:47:20 GMT-08:00

Influence of Reimbursement Policies on Dialysis Modality Distribution around the World

Brown, Edwina Anne — Thu, 13 Dec 2018 10:20:08 GMT-08:00

Fostering Innovation in Symptom Management among Hemodialysis Patients

Flythe, Jennifer E. — Mon, 05 Nov 2018 09:59:00 GMT-08:00

Individuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue.

An International Analysis of Dialysis Services Reimbursement

van der Tol, Arjan — Thu, 13 Dec 2018 10:20:08 GMT-08:00

Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney Disease

Garlo, Katherine G. — Fri, 28 Dec 2018 08:27:50 GMT-08:00

Patients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25–30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.

Utility of Electronic Medical Record Alerts to Prevent Drug Nephrotoxicity

Martin, Melissa — Thu, 05 Apr 2018 06:42:12 GMT-07:00

Nephrotoxin-induced AKI is an iatrogenic form of AKI that can be potentially avoided or ameliorated by prompt recognition and appropriate prescriber actions. Drug-targeted alerts, either for patients at risk of AKI or patients with existing AKI, may lead to more appropriate drug dosing and management and improved clinical outcomes. However, alerts of this type are complicated to create, have a high potential for error and off-target effects, and may be difficult to evaluate. Although many studies have shown that these alerts can reduce the rate of inappropriate prescribing, few studies have examined the utility of such alerts in terms of patient benefit. In this review, we examine the current state of the literature in this area, identify key technical challenges, and suggest methods of evaluation for drug-targeted AKI alerts.

Bleeding Complications after Pediatric Kidney Biopsy

Varnell, Charles D. — Thu, 06 Dec 2018 07:04:03 GMT-08:00

The Use of Selected Urine Chemistries in the Diagnosis of Kidney Disorders

Palmer, Biff F. — Wed, 09 Jan 2019 02:18:02 GMT-08:00

Urinary chemistries vary widely in both health and disease and are affected by diet, volume status, medications, and disease states. When properly examined, these tests provide important insight into the mechanism and therapy of various clinical disorders that are first detected by abnormalities in plasma chemistries. These tests cannot be interpreted in isolation, but instead require knowledge of key clinical information, such as medications, physical examination, and plasma chemistries, to include kidney function. When used appropriately and with knowledge of limitations, urine chemistries can provide important insight into the pathophysiology and treatment of a wide variety of disorders.

Diuretic use in incident ESKD

Wang, Ke — Wed, 19 Dec 2018 06:42:44 GMT-08:00

Patient and Caregiver Priorities for Outcomes in Peritoneal Dialysis

Manera, Karine E. — Thu, 20 Dec 2018 08:52:59 GMT-08:00

Association of Continuation of Loop Diuretics at Hemodialysis Initiation with Clinical Outcomes

Sibbel, Scott — Wed, 19 Dec 2018 06:42:43 GMT-08:00

Increasing Awareness of Early Risk of AKI in Neonates

Kamath, Nivedita — Thu, 31 Jan 2019 09:00:34 GMT-08:00

Blood Pressure Variability in CKD

Murphy, Daniel — Fri, 18 Jan 2019 08:36:27 GMT-08:00

Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGS

Yao, Tony — Tue, 15 Jan 2019 05:33:02 GMT-08:00

Clinical Pharmacology of Oral Anticoagulants in Patients with Kidney Disease

Jain, Nishank — Fri, 25 May 2018 07:36:53 GMT-07:00

Oral anticoagulants are commonly used drugs in patients with CKD and patients with ESKD to treat atrial fibrillation to reduce stroke and systemic embolism. Some of these drugs are used to treat or prevent deep venous thrombosis and pulmonary embolism in patients with CKD who undergo knee and hip replacement surgeries. Warfarin is the only anticoagulant that is approved for use by the Food and Drug Administration in individuals with mechanical heart valves. Each oral anticoagulant affects the coagulation profile in the laboratory uniquely. Warfarin and apixaban are the only anticoagulants that are Food and Drug Administration approved for use in patients with CKD and patients with ESKD. However, other oral anticoagulants are commonly used off label in this patient population. Given the acquired risk of bleeding from uremia, these drugs are known to cause increased bleeding events, hospitalization, and overall morbidity. Each anticoagulant has unique pharmacologic properties of which nephrologists need to be aware to optimally manage patients. In addition, nephrologists are increasingly asked to aid in the management of adverse bleeding events related to oral anticoagulant use in patients with CKD and patients with ESKD. This article summarizes the clinical pharmacology of these drugs and identifies knowledge gaps in the literature related to their use.

Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis

Stubbs, Jason R. — Mon, 21 Jan 2019 07:45:34 GMT-08:00

Variability in Cinacalcet Prescription across US Hemodialysis Facilities

Fuller, Douglas S. — Mon, 21 Jan 2019 07:45:33 GMT-08:00

Blood Pressure Variability, Mortality, and Cardiovascular Outcomes in CKD Patients

Mallamaci, Francesca — Wed, 02 Jan 2019 07:01:12 GMT-08:00

Medication Prescription Patterns for Secondary Hyperparathyroidism

Seethapathy, Harish — Mon, 21 Jan 2019 07:45:32 GMT-08:00

Does an Apple (or Many) Each Day, Keep Mortality Away?

Moorthi, Ranjani N. — Thu, 31 Jan 2019 09:00:35 GMT-08:00

Inadequate Dietary Potassium and Progression of CKD

DuBose, Thomas D. — Thu, 14 Feb 2019 05:53:10 GMT-08:00

Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis

Bobulescu, I. Alexandru — Mon, 11 Feb 2019 03:40:22 GMT-08:00

Correction

American Society of Nephrology — Thu, 20 Dec 2018 08:52:58 GMT-08:00

Enhanced Removal of Protein-Bound Uremic Toxins Using Displacers

Van Biesen, Wim — Wed, 06 Feb 2019 07:08:09 GMT-08:00

Differences in Dialysis Center Practices in Determining Hemodialysis Patient Postdialysis Target Weight and Patient Survival and Hospitalizations

Davenport, Andrew — Tue, 05 Feb 2019 06:51:23 GMT-08:00

Central Venous Stenosis, Access Outcome and Survival in Patients undergoing Maintenance Hemodialysis

Adwaney, Anamika — Thu, 14 Feb 2019 05:53:10 GMT-08:00

Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy

Thompson, Aliza — Fri, 11 Jan 2019 09:16:22 GMT-08:00

IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment’s effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment’s effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment’s effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.

Clinical Pharmacology in HIV Therapy

Atta, Mohamed G. — Tue, 29 May 2018 07:21:32 GMT-07:00

The success of combination antiretroviral therapy in the treatment of HIV-1–positive individuals has shifted clinical attention toward combination antiretroviral drug regimens that optimize tolerability, long-term safety, and durable efficacy. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non–HIV-associated comorbidities, which may be observed earlier than in age-matched controls and despite the best available combination antiretroviral therapy. Similarly, HIV-1–positive individuals are now diagnosed and treated earlier with anticipated lifelong therapy. The contribution of specific antiretroviral agents to long-term morbidity and mortality is dependent on the pharmacologic characteristics of these agents, and it is increasingly important in this context.

Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient Outcomes

Dasgupta, Indranil — Tue, 05 Feb 2019 06:51:23 GMT-08:00

Buttonhole versus Stepladder Cannulation for Home Hemodialysis

Huang, Shih-Han S. — Fri, 18 Jan 2019 08:36:27 GMT-08:00

Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor

Madero, Magdalena — Tue, 12 Feb 2019 07:06:19 GMT-08:00

Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and Microalbuminuria

Ito, Sadayoshi — Tue, 12 Feb 2019 07:06:19 GMT-08:00

The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease

Bressendorff, Iain — Tue, 21 Aug 2018 05:47:50 GMT-07:00

Magnesium Concentration in Dialysate

Floege, Jürgen — Tue, 21 Aug 2018 05:47:50 GMT-07:00

Dementia in Dialysis

Weintraub, Judy — Thu, 09 Aug 2018 09:22:40 GMT-07:00

Determinants of Arteriovenous Fistula Maturation

Hentschel, Dirk M. — Thu, 23 Aug 2018 06:23:54 GMT-07:00

Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis Initiation

McAdams-DeMarco, Mara A. — Thu, 09 Aug 2018 09:22:40 GMT-07:00

Regulatory Considerations for Hemodiafiltration in the United States

Ward, Richard A. — Tue, 06 Mar 2018 06:04:23 GMT-08:00

Online hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10−6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.

Clinical Pharmacodynamics

Keller, Frieder — Wed, 16 May 2018 08:01:30 GMT-07:00

Pharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is found, but pharmacodynamics is as important. Alterations of pharmacodynamic parameters are conceivable but only rarely reported in kidney failure. Sometimes surprising dosing adjustments are needed when pharmacodynamic concepts are brought into the decision process of which dose to choose. Pharmacokinetics and pharmacodynamics should both be considered when any dosing regimen is determined.

Gut-Derived Metabolites and Chronic Kidney Disease

Vanholder, Raymond — Tue, 07 Aug 2018 08:07:05 GMT-07:00

Circumstances of Death among Undocumented Immigrants Who Rely on Emergency-Only Hemodialysis

Cervantes, Lilia — Fri, 13 Jul 2018 12:26:28 GMT-07:00

IgA Nephropathy Susceptibility Loci and Disease Progression

Shi, Manman — Tue, 24 Jul 2018 01:47:04 GMT-07:00

Characteristics of Colon-Derived Uremic Solutes

Mair, Robert D. — Tue, 07 Aug 2018 08:07:06 GMT-07:00

Variations in 24-Hour BP Profiles in Cohorts of Patients with Kidney Disease around the World

Drawz, Paul E. — Thu, 05 Jul 2018 05:09:31 GMT-07:00

Hemodiafiltration to Address Unmet Medical Needs ESKD Patients

Canaud, Bernard — Tue, 06 Mar 2018 06:04:22 GMT-08:00

Hemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient’s blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.

Association of Preexisting Arterial Intimal Hyperplasia with Arteriovenous Fistula Outcomes

Allon, Michael — Thu, 23 Aug 2018 06:23:53 GMT-07:00

Association of Urinary Biomarkers of Kidney Injury with Estimated GFR Decline in HIV-Infected Individuals following Tenofovir Disoproxil Fumarate Initiation

Ascher, Simon B. — Tue, 28 Aug 2018 07:51:51 GMT-07:00

Postoperative Ultrasound, Unassisted Maturation, and Subsequent Primary Patency of Arteriovenous Fistulas

Farrington, Crystal A. — Thu, 23 Aug 2018 06:23:55 GMT-07:00

Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis Facilities

D’Agata, Erika M.C. — Thu, 23 Aug 2018 06:23:54 GMT-07:00

Two-Year Observational Study of Bloodstream Infection Rates in Hemodialysis Facility Patients with and without Catheters

Brown, Robert S. — Fri, 07 Sep 2018 01:00:24 GMT-07:00

Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney Disease

Chettiar, Alexis — Thu, 19 Jul 2018 05:51:09 GMT-07:00

Drug Coated Balloon Angioplasty in Failing AV Fistulas

Trerotola, Scott O. — Tue, 24 Jul 2018 01:47:04 GMT-07:00

Commentary on Complications of Immunosuppressive Treatments for Glomerulonephritis

Kestenbaum, Bryan R. — Tue, 24 Jul 2018 01:47:05 GMT-07:00

Metabolic Changes with Base-Loading in CKD

Scialla, Julia J. — Fri, 22 Jun 2018 06:19:45 GMT-07:00

Proximal Tubular Secretory Clearance

Wang, Ke — Wed, 28 Feb 2018 07:15:55 GMT-08:00

The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.

Complications of Immunosuppression in Glomerular Disease

Jefferson, J. Ashley — Tue, 24 Jul 2018 01:47:03 GMT-07:00

Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.

Alteration of HDL Protein Composition with Hemodialysis Initiation

Wang, Ke — Wed, 25 Jul 2018 10:04:32 GMT-07:00

Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

Edwards, Marie E. — Thu, 19 Jul 2018 05:51:10 GMT-07:00

Cost of Dialysis Therapy by Modality in Manitoba

Beaudry, Alain — Wed, 18 Jul 2018 06:16:05 GMT-07:00

End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis Therapy

Chen, Joy Chieh-Yu — Thu, 19 Jul 2018 05:51:09 GMT-07:00

Meeting the Palliative Care Needs of Maintenance Hemodialysis Patients

Grubbs, Vanessa — Thu, 19 Jul 2018 05:51:08 GMT-07:00

Characterizing Approaches to Dialysis Decision Making with Older Adults

Ladin, Keren — Thu, 26 Jul 2018 06:21:31 GMT-07:00

Clinical Pharmacokinetics in Kidney Disease

Roberts, Darren M. — Tue, 24 Jul 2018 01:47:03 GMT-07:00

A change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug’s properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.

Person-Centered Approach to Deciding on Long-Term Dialysis

Eilers, Denise — Thu, 26 Jul 2018 06:21:30 GMT-07:00

Correction

American Society of Nephrology — Fri, 15 Jun 2018 07:25:44 GMT-07:00

Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease

Fishbane, Steven — Tue, 19 Jun 2018 08:09:52 GMT-07:00

Drug-Coated Balloon Angioplasty for Hemodialysis Fistula Maintenance

Sachdeva, Bharat — Tue, 24 Jul 2018 01:47:04 GMT-07:00

COL4A3 Gene Variants and Diabetic Kidney Disease in MODY

Wang, Yiting — Mon, 16 Jul 2018 07:44:52 GMT-07:00

Ptolemy and Copernicus Revisited

Coca, Steven G. — Thu, 17 May 2018 06:08:05 GMT-07:00

Donor Outcomes

Saunders, Milda R. — Thu, 31 May 2018 07:11:29 GMT-07:00

Living Donation

Díaz-González de Ferris, Maria E. — Thu, 31 May 2018 07:11:28 GMT-07:00

Comparative Effects of Cholecalciferol and Calcitriol on Circulating Markers of CKD Mineral Bone Disorder

Zelnick, Leila R. — Wed, 07 Mar 2018 05:44:58 GMT-08:00

Identifying Outcomes that Are Important to Living Kidney Donors

Hanson, Camilla S. — Thu, 31 May 2018 07:11:29 GMT-07:00

Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis Patients

Tonelli, Marcello — Thu, 29 Mar 2018 06:09:57 GMT-07:00

Association between Duration of Predialysis Care and Mortality after Dialysis Start

Liu, Ping — Mon, 05 Mar 2018 07:48:22 GMT-08:00

Prevalence of Hypertension in Children with Early-Stage ADPKD

Massella, Laura — Thu, 19 Apr 2018 07:58:40 GMT-07:00

Teaching Pediatric Peritoneal Dialysis Globally through Virtual Simulation

Olszewski, Aleksandra E. — Wed, 02 May 2018 05:56:47 GMT-07:00

Race in America

Tuttle, Katherine R. — Thu, 24 May 2018 06:17:07 GMT-07:00

Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes

Gerber, Claire — Thu, 24 May 2018 06:17:08 GMT-07:00

Clear the Fog around Parathyroid Hormone Assays

Hocher, Berthold — Mon, 05 Mar 2018 07:48:22 GMT-08:00

Community-Based CKD Screening in Black Americans

Norris, Keith C. — Thu, 15 Mar 2018 06:59:34 GMT-07:00

Metabolic and Hypertensive Complications of Pregnancy in Women with Nephrolithiasis

Tangren, Jessica Sheehan — Thu, 22 Feb 2018 07:39:25 GMT-08:00

β-Blocker Dialyzability in Maintenance Hemodialysis Patients

Tieu, Alvin — Thu, 08 Mar 2018 10:12:42 GMT-08:00

Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults

Dobre, Mirela — Thu, 22 Mar 2018 05:49:23 GMT-07:00

Treatment of Severe Hyponatremia

Sterns, Richard H. — Tue, 02 Jan 2018 10:59:16 GMT-08:00

Patients with severe (serum sodium ≤120 mEq/L), symptomatic hyponatremia can develop life-threatening or fatal complications from cerebral edema if treatment is inadequate and permanent neurologic disability from osmotic demyelination if treatment is excessive. Unfortunately, as is true of all electrolyte disturbances, there are no randomized trials to guide the treatment of this challenging disorder. Rather, therapeutic decisions rest on physiologic principles, animal models, observational studies, and single-patient reports. European guidelines and recommendations of an American Expert panel have come to similar conclusions on how much correction of hyponatremia is enough and how much is too much, but there are important differences. We review the evidence supporting these recommendations, identifying areas that rest on relatively solid ground and highlighting areas in greatest need of additional data.

Systems Thinking and Leadership

Wong, Leslie P. — Thu, 22 Mar 2018 05:49:24 GMT-07:00

Infections are the second leading cause of death for patients with ESKD. Despite multiple efforts, nephrologists have been unable to prevent infections in dialysis facilities. The American Society of Nephrology and the Centers for Disease Control and Prevention have partnered to create Nephrologists Transforming Dialysis Safety to promote nephrologist leadership and engagement in efforts to “Target Zero” preventable dialysis infections. Because traditional approaches to infection control and prevention in dialysis facilities have had limited success, Nephrologists Transforming Dialysis Safety is reconceptualizing the problem in the context of the complexity of health care systems and organizational behavior. By identifying different parts of a problem and attempting to understand how these parts interact and produce a result, systems thinking has effectively tackled difficult problems in dynamic settings. The dialysis facility is composed of different physical and human elements that are interconnected and affect not only behavior but also, the existence of a culture of safety that promotes infection prevention. Because dialysis infections result from a complex system of interactions between caregivers, patients, dialysis organizations, and the environment, attempts to address infections by focusing on one element in isolation often fail. Creating a sense of urgency and commitment to eradicating dialysis infections requires leadership and motivational skills. These skills are not taught in the standard nephrology or medical director curriculum. Effective leadership by medical directors and engagement in infection prevention by nephrologists are required to create a culture of safety. It is imperative that nephrologists commit to leadership training and embrace their potential as change agents to prevent infections in dialysis facilities. This paper explores the systemic factors contributing to the ongoing dialysis infection crisis in the United States and the role of nephrologists in instilling a culture of safety in which infections can be anticipated and prevented.

The Role of Bicarbonate in Cognition

Sozio, Stephen M. — Thu, 22 Mar 2018 05:49:23 GMT-07:00

Commentary on Treatment of Severe Hyponatremia

Seliger, Stephen — Tue, 02 Jan 2018 10:59:15 GMT-08:00

Central Blood Pressure and Cardiovascular Outcomes in Chronic Kidney Disease

Rahman, Mahboob — Fri, 23 Feb 2018 11:41:49 GMT-08:00

Performance on the Nephrology In-Training Examination and ABIM Nephrology Certification Examination Outcomes

Jurich, Daniel — Wed, 28 Feb 2018 07:15:54 GMT-08:00

The Effect of Learning Styles on Adverse Events in Home Hemodialysis Patients

Auguste, Bourne L. — Mon, 16 Apr 2018 07:17:07 GMT-07:00

Survey of Kidney Biopsy Clinical Practice and Training in the United States

Yuan, Christina M. — Wed, 18 Apr 2018 07:10:55 GMT-07:00

Antimalarial Drugs for the Prevention of Chronic Kidney Disease in Patients with Rheumatoid Arthritis

Rodrigues, Jennifer C. — Mon, 16 Apr 2018 07:17:07 GMT-07:00

Is There a Need for Additional DQ Matching?

Süsal, Caner — Mon, 23 Apr 2018 05:36:44 GMT-07:00

Symptom Prioritization among Adults Receiving In-Center Hemodialysis

Flythe, Jennifer E. — Tue, 20 Mar 2018 06:45:41 GMT-07:00

Long-Term Consequences of Acute Kidney Injury in Children

Sutherland, Scott M. — Fri, 20 Apr 2018 07:37:14 GMT-07:00

Does the Kidney Biopsy Portend the Future of Nephrology?

Gilbert, Scott J. — Wed, 18 Apr 2018 07:10:54 GMT-07:00

Opioid Analgesics and Adverse Outcomes among Hemodialysis Patients

Ishida, Julie H. — Thu, 19 Apr 2018 07:58:40 GMT-07:00

Appropriate Use of Opioids in Patients with Kidney Diseases

White, David M. — Thu, 19 Apr 2018 07:58:40 GMT-07:00

Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes

Schroeder, Emily B. — Fri, 23 Mar 2018 05:56:14 GMT-07:00

Pharmacology behind Common Drug Nephrotoxicities

Perazella, Mark A. — Thu, 05 Apr 2018 06:42:13 GMT-07:00

Patients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various agents administered enhance risk for drug-induced nephrotoxicity. This paper will review these clinically relevant aspects of drug-induced nephrotoxicity for the clinical nephrologist.

Correction

American Society of Nephrology — Fri, 09 Nov 2018 05:47:19 GMT-08:00

Home-Based Care for CKD for High-Risk Populations

Rodgers, Wendy — Thu, 15 Nov 2018 07:48:00 GMT-08:00

Health Insurance in the First 3 Months of Hemodialysis and Early Vascular Access

Lin, Eugene — Thu, 01 Nov 2018 09:08:47 GMT-07:00

Procurement Biopsies in the Evaluation of Deceased Donor Kidneys

Carpenter, Dustin — Thu, 25 Oct 2018 02:00:13 GMT-07:00

Does What Goes Around Always Come Around?

Trachtman, Howard — Thu, 15 Nov 2018 07:47:58 GMT-08:00

Persistent Hematuria in ANCA Vasculitis

Mahoney, Shannon L. — Thu, 25 Jan 2018 06:03:51 GMT-08:00

Anion Gap as a Determinant of Ionized Fraction of Divalent Cations in Hemodialysis Patients

Sakaguchi, Yusuke — Mon, 27 Nov 2017 06:42:21 GMT-08:00

Why Nomenclature for Pharmacist-Led Interventions Matters

Pai, Amy Barton — Tue, 02 Jan 2018 10:59:16 GMT-08:00

Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome

Legrand, Anne — Thu, 16 Nov 2017 06:49:11 GMT-08:00

Employment among Patients on Dialysis

Hallab, Ayman — Thu, 18 Jan 2018 07:19:29 GMT-08:00

Medicare’s New Prospective Payment System on Facility Provision of Peritoneal Dialysis

Wang, Virginia — Mon, 19 Nov 2018 07:17:42 GMT-08:00

Novel Models for Health Care Delivery for CKD for Disadvantaged Populations

Lunyera, Joseph — Thu, 15 Nov 2018 07:47:59 GMT-08:00

Clinical and Regulatory Considerations for Central Venous Catheters for Hemodialysis

Silverstein, Douglas M. — Thu, 11 Oct 2018 05:36:10 GMT-07:00

Central venous catheters remain a vital option for access for patients receiving maintenance hemodialysis. There are many important and evolving clinical and regulatory considerations for all stakeholders for these devices. Innovation and transparent and comprehensive regulatory review of these devices is essential to stimulate innovation to help promote better outcomes for patients receiving maintenance hemodialysis. A workgroup that included representatives from academia, industry, and the US Food and Drug Administration was convened to identify the major design considerations and clinical and regulatory challenges of central venous catheters for hemodialysis. Our intent is to foster improved understanding of these devices and provide the foundation for strategies to foster innovation of these devices.

Monoclonal Gammopathies and Kidney Disease

Wang, Christina Hao — Thu, 15 Nov 2018 07:47:58 GMT-08:00

Treatment of Drug-Induced Acute Tubulointerstitial Nephritis

Moledina, Dennis G. — Mon, 05 Nov 2018 09:59:01 GMT-08:00

Prevalence of Opioid, Gabapentinoid, and NSAID Use in Patients with CKD

Novick, Tessa K. — Thu, 08 Nov 2018 06:21:10 GMT-08:00

Still Asking “Which Rate Is Right?” Years Later

Woodell, Tyler B. — Thu, 29 Nov 2018 07:49:44 GMT-08:00

Facility-Level Variations in Kidney Disease Care among Veterans with Diabetes and CKD

Navaneethan, Sankar D. — Thu, 29 Nov 2018 07:49:44 GMT-08:00

Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite Profiles

Kalim, Sahir — Wed, 14 Feb 2018 06:44:28 GMT-08:00

Twenty-Four–Hour Ambulatory Blood Pressure versus Clinic Blood Pressure Measurements and Risk of Adverse Outcomes in Children with CKD

Ku, Elaine — Tue, 13 Feb 2018 07:28:17 GMT-08:00

Rest Easy with Intravenous Iron for Dialysis Patients?

Li, Xiaojuan — Tue, 20 Feb 2018 07:08:12 GMT-08:00

Serum Sodium and Cognition in Older Community-Dwelling Men

Nowak, Kristen L. — Thu, 08 Feb 2018 05:51:07 GMT-08:00

Neurocognitive and Educational Outcomes in Children and Adolescents with CKD

Chen, Kerry — Thu, 22 Feb 2018 07:39:26 GMT-08:00

Definitions and End Points for Interventional Studies for Arteriovenous Dialysis Access

Beathard, Gerald A. — Thu, 20 Jul 2017 01:51:37 GMT-07:00

This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access’ evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1—patent arteriovenous access, stage 2—physiologically mature arteriovenous access, and stage 3—clinically functional arteriovenous access. Once the requirements of a stage 3—clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.

FDA Regulatory Perspectives for Studies on Hemodialysis Vascular Access

Hurst, Frank P. — Mon, 24 Jul 2017 06:07:47 GMT-07:00

In an effort to foster innovation and new product development, the American Society of Nephrology and the US Food and Drug Administration partnered to form the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative’s mission is to foster development of therapies by creating a collaborative environment where the US Food and Drug Administration and the greater nephrology community can interact to optimize product evaluation. This particular Kidney Health Initiative project focused on products related to hemodialysis vascular access, with the goal of clarifying appropriate trial end points that could subsequently inform clinical, regulatory, and coverage decisions. Both the lack of common definitions and the lack of consensus on trial end points have been viewed as barriers to innovation in this area. Toward this end, the Kidney Health Initiative convened teams of expert stakeholders to address these issues for each major vascular access category (arteriovenous grafts, arteriovenous fistulas, and central venous catheters), and each team provided recommendations. This commentary provides an overview of the US Food and Drug Administration centers that regulate hemodialysis vascular access and certain laws and regulations that affect these products as well as our perspectives on some of the issues raised and end points proposed by the Kidney Health Initiative teams. The standardized definitions and clinical trial end points proposed by the teams represent an important step forward to improve innovation in this area.

Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator Hemodialysis Catheter Locking Solution

Hemmelgarn, Brenda R. — Mon, 15 Jan 2018 09:38:04 GMT-08:00

Responsive Designed Interventions Are Needed to Support Positive Outcomes of Children and Adolescents with CKD

Hartwell, Lori M. — Thu, 22 Feb 2018 07:39:25 GMT-08:00

Safety of Intravenous Iron in Dialysis

Hougen, Ingrid — Tue, 20 Feb 2018 07:08:13 GMT-08:00

Recommended Clinical Trial End Points for Dialysis Catheters

Allon, Michael — Thu, 20 Jul 2017 01:51:36 GMT-07:00

Central venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.

Clinical Trial End Points for Hemodialysis Vascular Access

Shenoy, Surendra — Tue, 27 Feb 2018 08:03:55 GMT-08:00

Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center Hemodialysis

Rivara, Matthew B. — Thu, 11 Jan 2018 11:49:59 GMT-08:00

Intensive Hemodialysis Fails to Reduce Plasma Levels of Uremic Solutes

Sirich, Tammy L. — Wed, 14 Feb 2018 06:44:28 GMT-08:00

The Enigma of Blood Pressure Measurement in Children with CKD

Falkner, Bonita — Tue, 13 Feb 2018 07:28:17 GMT-08:00

Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes

Garlo, Katherine G. — Tue, 16 Jan 2018 06:07:31 GMT-08:00

ACCORDION: Ensuring That We Hear the Music Clearly

Wong, Muh Geot — Thu, 25 Oct 2018 02:00:11 GMT-07:00

Kidney Function Reserve Capacity in Early and Later Stage Autosomal Dominant Polycystic Kidney Disease

Messchendorp, A. Lianne — Tue, 25 Sep 2018 07:56:06 GMT-07:00

MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access

Wu, Chih-Cheng — Fri, 21 Sep 2018 06:27:11 GMT-07:00

High-Dose Seasonal Influenza Vaccine in Patients Undergoing Dialysis

Miskulin, Dana C. — Tue, 23 Oct 2018 07:00:25 GMT-07:00

Changes in Transfusion Coding Among Hospitalized Medicare Beneficiaries after Implementation of ICD-10

Weinhandl, Eric D. — Tue, 16 Oct 2018 07:57:47 GMT-07:00

Kidney Biopsy in Hospitalized Patients with Acute Kidney Disease

Weisbord, Steven Darrow — Mon, 22 Oct 2018 07:26:59 GMT-07:00

Medication Safety Principles and Practice in CKD

Whittaker, Chanel F. — Mon, 18 Jun 2018 08:20:52 GMT-07:00

Ensuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.

Treatment Adherence in Young Adults Receiving Kidney Replacement Therapy

Duquette, Pam — Tue, 16 Oct 2018 07:57:46 GMT-07:00

Increasing Protection of Dialysis Patients against Influenza

Lindley, Megan C. — Tue, 23 Oct 2018 07:00:24 GMT-07:00

Urea for the Treatment of Hyponatremia

Rondon-Berrios, Helbert — Tue, 04 Sep 2018 06:32:18 GMT-07:00

Associations with Wellbeing and Medication Adherence in Young Adults Receiving Kidney Replacement Therapy

Hamilton, Alexander James — Tue, 16 Oct 2018 07:57:48 GMT-07:00

Treatment Adherence in Young Adults Receiving Kidney Replacement Therapy

Grandinetti, Amanda — Tue, 16 Oct 2018 07:57:48 GMT-07:00

Better Patient Ambulatory Care Experience

Tuot, Delphine S. — Thu, 18 Oct 2018 07:16:24 GMT-07:00

Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney Outcomes

Mottl, Amy K. — Thu, 25 Oct 2018 02:00:12 GMT-07:00

Accessing the Access

Zimmerman, Deborah — Thu, 13 Sep 2012 08:04:47 GMT-07:00

Fluid First or Not So Fast: Ultrafiltration Rate and the ESRD Quality Incentive Program

Weiner, Daniel E. — Wed, 22 Jun 2016 06:42:58 GMT-07:00

Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility Implications

Flythe, Jennifer E. — Wed, 22 Jun 2016 06:42:59 GMT-07:00

Provider Knowledge, Attitudes, and Practices Surrounding Conservative Management for Patients with Advanced CKD

Parvez, Sanah — Fri, 15 Apr 2016 09:07:54 GMT-07:00

Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis

Verde, Eduardo — Mon, 03 Oct 2016 08:49:28 GMT-07:00

Managing Disruptive Behavior by Patients and Physicians: A Responsibility of the Dialysis Facility Medical Director

Jones, Edward R. — Mon, 17 Nov 2014 07:02:45 GMT-08:00

The Centers for Medicare & Medicaid Services’ Conditions for Coverage make the medical director of an ESRD facility responsible for all aspects of care, including high-quality health care delivery (e.g., safe, effective, timely, efficient, and patient centered). Because of the high-pressure environment of the dialysis facility, conflicts are common. Conflict frequently occurs when aberrant behaviors disrupt the dialysis facility. Patients, family members, friends, and, less commonly appreciated, nephrology clinicians (i.e., nephrologists and advanced care practitioners) may manifest disruptive behavior. Disruptive behavior in the dialysis facility impairs the ability to deliver high-quality care. Furthermore, disruptive behavior is the leading cause for involuntary discharge (IVD) or involuntary transfer (IVT) of a patient from a facility. IVD usually results in loss of continuity of care, increased emergency department visits, and increased unscheduled, acute dialysis treatments. A sufficient number of IVDs and IVTs also trigger an extensive review of the facility by the regional ESRD Networks, exposing the facility to possible Medicare-imposed sanctions. Medical directors must be equipped to recognize and correct disruptive behavior. Nephrology-based literature and tools exist to help dialysis facility medical directors successfully address and resolve disruptive behavior before medical directors must involuntarily discharge a patient or terminate an attending clinician.

The Medical Director in Integrated Clinical Care Models

Parker, Thomas F. — Tue, 28 Oct 2014 07:56:54 GMT-07:00

Integrated clinical care models, like Accountable Care Organizations and ESRD Seamless Care Organizations, present new opportunities for dialysis facility medical directors to affect changes in care that result in improved patient outcomes. Currently, there is little scholarly information on what role the medical director should play. In this opinion-based review, it is predicted that dialysis providers, the hospitals in which the medical director and staff physicians practice, and the payers with which they contract are going to insist that, as care becomes more integrated, dialysis facility medical directors participate in new ways to improve quality and decrease the costs of care. Six broad areas are proposed where dialysis unit medical directors can have the greatest effect on shifting the quality-care paradigm where integrated care models are used. The medical director will need to develop an awareness of the regional medical care delivery system, collect and analyze actionable data, determine patient outcomes to be targeted that are mutually agreed on by participating physicians and institutions, develop processes of care that result in improved patient outcomes, and lead and inform the medical staff. Three practical examples of patient-centered, quality-focused programs developed and implemented by dialysis unit medical directors and their practice partners that targeted dialysis access, modality choice, and fluid volume management are presented. Medical directors are encouraged to move beyond traditional roles and embrace responsibilities associated with integrated care.

Infection Prevention and the Medical Director: Uncharted Territory

Kapoian, Toros — Fri, 20 Feb 2015 06:37:53 GMT-08:00

Infections continue to be a major cause of disease and contributor to death in patients on dialysis. Despite our knowledge and acceptance that hemodialysis catheters should be avoided and eliminated, most patients who begin dialysis initiate treatment through a central vein hemodialysis catheter. Dialysis Medical Directors must be the instrument through which our industry changes. We must lead the charge to educate our dialysis staff and our dialysis patients. We must also educate ourselves so that we not only know that our facility policies are consistent with the best evidence available, but we must also know where local and federal regulations differ. When these differences impact on patient care, we must speak out and have these regulations changed. But it is not enough to know the rules and write them. We must lead by example and show our patients, our nephrology colleagues and our dialysis staff that we always follow these same policies. We need to practice what we preach and be willing and available to redirect those individuals who have difficulty following the rules. In order to effectively change process meaningful data must be collected, analyzed and acted upon. Dialysis Medical Directors must direct and lead the quality improvement process. We hope this review provides Dialysis Medical Directors with the necessary tools to effectively drive this process and improve care.

Associations of Posthemodialysis Weights above and below Target Weight with All-Cause and Cardiovascular Mortality

Flythe, Jennifer E. — Fri, 10 Apr 2015 10:00:22 GMT-07:00

Posthemodialysis Weights and Mortality: Another Narrow Range Target?

Jablonski, Kristen L. — Fri, 10 Apr 2015 10:00:24 GMT-07:00

What Medical Directors Need to Know about Dialysis Facility Water Management

Kasparek, Ted — Fri, 15 May 2015 07:18:13 GMT-07:00

The medical directors of dialysis facilities have many operational clinic responsibilities, which on first glance, may seem outside the realm of excellence in patient care. However, a smoothly running clinic is integral to positive patient outcomes. Of the conditions for coverage outlined by the Centers for Medicare and Medicaid Services, one most critical to quality dialysis treatment is the provision of safe purified dialysis water, because there are many published instances where clinic failure in this regard has resulted in patient harm. As the clinical leader of the facility, the medical director is obliged to have knowledge of his/her facility’s water treatment system to reliably ensure that the purified water used in dialysis will meet the standards for quality set by the Association for the Advancement of Medical Instrumentation and used by the Centers for Medicare and Medicaid Services for conditions for coverage. The methods used to both achieve and maintain these quality standards should be a part of quality assessment and performance improvement program meetings. The steps for water treatment, which include pretreatment, purification, and distribution, are largely the same, regardless of the system used. Each water treatment system component has a specific role in the process and requires individualized maintenance and monitoring. The medical director should provide leadership by being engaged with the process, knowing the facility’s source water, and understanding water treatment system operation as well as the clinical significance of system failure. Successful provision of quality water will be achieved by those medical directors who learn, know, and embrace the requirements of dialysis water purification and system maintenance.

American Society of Nephrology Quiz and Questionnaire 2014: RRT

Mehrotra, Rajnish — Mon, 20 Apr 2015 09:20:15 GMT-07:00

The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology (ASN). Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, end-stage renal disease/dialysis, and transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Prior to the meeting, program directors of U.S. nephrology training programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors (TPDs). The correct and incorrect answers were then discussed after the audience responses and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis

Ogna, Adam — Fri, 10 Apr 2015 10:00:21 GMT-07:00

Maintaining Safety in the Dialysis Facility

Kliger, Alan S. — Thu, 06 Nov 2014 06:42:34 GMT-08:00

Errors in dialysis care can cause harm and death. While dialysis machines are rarely a major cause of morbidity, human factors at the machine interface and suboptimal communication among caregivers are common sources of error. Major causes of potentially reversible adverse outcomes include medication errors, infections, hyperkalemia, access-related errors, and patient falls. Root cause analysis of adverse events and "near misses" can illuminate care processes and show system changes to improve safety. Human factors engineering and simulation exercises have strong potential to define common clinical team purpose, and improve processes of care. Patient observations and their participation in error reduction increase the effectiveness of patient safety efforts.

The Medical Director and Quality Requirements in the Dialysis Facility

Schiller, Brigitte — Thu, 06 Nov 2014 06:42:32 GMT-08:00

Four decades after the successful implementation of the ESRD program currently providing life-saving dialysis therapy to >430,000 patients, the definitions of and demands for a high-quality program have evolved and increased at the same time. Through substantial technological advances ESRD care improved, with a predominant focus on the technical aspects of care and the introduction of medications such as erythropoiesis-stimulating agents and active vitamin D for anemia and bone disease management. Despite many advances, the size of the program and the increasingly older and multimorbid patient population have contributed to continuing challenges for providing consistently high-quality care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define the medical director of the dialysis center as the leader of the interdisciplinary team and the person ultimately accountable for quality, safety, and care provided in the center. Knowledge and active leadership with a hands-on approach in the quality assessment and performance improvement process (QAPI) is essential for the achievement of high-quality outcomes in dialysis centers. A collaborative approach between the dialysis provider and medical director is required to optimize outcomes and deliver evidence-based quality care. In 2011 the Centers for Medicare & Medicaid Services introduced a pay-for-performance program—the ESRD quality incentive program (QIP)— with yearly varying quality metrics that result in payment reductions in subsequent years when targets are not achieved during the performance period. Success with the QIP requires a clear understanding of the structure, metrics, and scoring methods. Information on achievement and nonachievement is publicly available, both in facilities (through the facility performance score card) and on public websites (including Medicare’s Dialysis Facility Compare). By assuming the leadership role in the quality program of dialysis facilities, the medical director is given an important opportunity to improve patients’ lives and effect true change in a patient population dealing with a very challenging chronic disease. This article in the series on the role of the medical director summarizes the medical director’s specific role in the quality improvement process in the dialysis facility and the associated requirements and programs, including QAPI and QIP.

Disparities in Electronic Health Record Patient Portal Use in Nephrology Clinics

Jhamb, Manisha — Thu, 22 Oct 2015 07:05:21 GMT-07:00

Introduction: Role of the Medical Director Series

Provenzano, Robert — Mon, 12 Jan 2015 06:54:16 GMT-08:00

The Evolving Role of the Medical Director of a Dialysis Facility

Maddux, Franklin W. — Thu, 02 Oct 2014 12:56:17 GMT-07:00

The medical director has been a part of the fabric of Medicare’s ESRD program since entitlement was extended under Section 299I of Public Law 92-603, passed on October 30, 1972, and implemented with the Conditions for Coverage that set out rules for administration and oversight of the care provided in the dialysis facility. The role of the medical director has progressively increased over time to effectively extend to the physicians serving in this role both the responsibility and accountability for the performance and reliability related to the care provided in the dialysis facility. This commentary provides context to the nature and expected competencies and behaviors of these medical director roles that remain central to the delivery of high-quality, safe, and efficient delivery of RRT, which has become much more intensive as the dialysis industry has matured.

Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics

Nasr, Samih H. — Tue, 14 Apr 2015 10:56:29 GMT-07:00

Amyloidosis derived from leukocyte cell–derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell–derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell–derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell–derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis as Ig light chain–derived amyloidosis to avoid harmful chemotherapy.

Medical Director Responsibilities to the ESRD Network

DeOreo, Peter B. — Thu, 25 Sep 2014 04:42:28 GMT-07:00

The 18 regional ESRD Networks are established in legislation and contract with the Centers for Medicare and Medicaid Services to improve the quality and safety of dialysis, maximize patient rehabilitation, encourage collaboration among and between providers toward common quality goals, and improve the reliability and the use of data in pursuit of quality improvement. The Networks are funded by a $0.50 per treatment fee deducted from the reimbursement to dialysis providers, and their deliverables are determined by a statement of work, which is updated in a new contract every 3 years. The Conditions for Coverage require dialysis providers to participate in Network activities, and failure to do so can be the basis for sanctions against the provider. However, the Networks attempt to foster a collegial relationship with dialysis facilities by offering tools, educational activities, and other resources to assist the facilities in meeting the evolving requirements by the Centers for Medicare and Medicaid Services on the basis of national aims and domains for quality improvement in health care that transcend the ESRD program. Because of his/her responsibility for implementing the quality assessment and performance improvement activities in the facility, the medical director has much to gain by actively participating in Network activities, especially those focused on quality, safety, patient grievance, patient engagement, and coordination of care. Membership on Network committees can also foster the professional growth of the medical director through participation in quality improvement activity development and implementation, authorship of articles in peer-reviewed journals, creation of educational tools and presentations, and application of Network-sponsored materials to improve patient outcomes, engagement, and satisfaction in the medical director’s facility. The improvement of care of patients on dialysis will be beneficial to the facility in achieving its goals of quality, safety, and financial viability.

Developing Risk Prediction Models for Kidney Injury and Assessing Incremental Value for Novel Biomarkers

Kerr, Kathleen F. — Thu, 22 May 2014 09:35:47 GMT-07:00

The field of nephrology is actively involved in developing biomarkers and improving models for predicting patients’ risks of AKI and CKD and their outcomes. However, some important aspects of evaluating biomarkers and risk models are not widely appreciated, and statistical methods are still evolving. This review describes some of the most important statistical concepts for this area of research and identifies common pitfalls. Particular attention is paid to metrics proposed within the last 5 years for quantifying the incremental predictive value of a new biomarker.

Vascular Effects of Exercise Training in CKD: Current Evidence and Pathophysiological Mechanisms

Van Craenenbroeck, Amaryllis H. — Thu, 15 May 2014 08:29:57 GMT-07:00

Cardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group.

Which Patients Benefit from Initiation of Dialysis for AKI?

Pannu, Neesh — Thu, 20 Mar 2014 11:56:15 GMT-07:00

Propagating the Nephrology Research Workforce: A Kidney Research National Dialogue Training Commentary

Kohan, Donald E. — Thu, 13 Mar 2014 09:35:09 GMT-07:00

The National Institute of Diabetes and Digestive and Kidney Diseases conducted the Kidney Research National Dialogue as an interactive means to formulate and prioritize research goals necessary to address the needs of patients with renal disease. This commentary summarizes the discussion and priorities arising from the training domain of the dialogue and posits three overall strategies to broaden the nephrology research workforce pipeline. The community needs to recruit and provide support for mentors in nephrology, target medical and graduate students earlier in their education for exposure to renal research, and expand the research workforce to include basic scientists from many disciplines as well as under-represented minorities.

Improving Outcomes for ESRD Patients: Shifting the Quality Paradigm

Nissenson, Allen R. — Thu, 07 Nov 2013 03:34:02 GMT-08:00

The availability of life-saving dialysis therapy has been one of the great successes of medicine in the past four decades. Over this time period, despite treatment of hundreds of thousands of patients, the overall quality of life for patients with ESRD has not substantially improved. A narrow focus by clinicians and regulators on basic indicators of care, like dialysis adequacy and anemia, has consumed time and resources but not resulted in significantly improved survival; also, frequent hospitalizations and dissatisfaction with the care experience continue to be seen. A new quality paradigm is needed to help guide clinicians, providers, and regulators to ensure that patients’ lives are improved by the technically complex and costly therapy that they are receiving. This paradigm can be envisioned as a quality pyramid: the foundation is the basic indicators (outstanding performance on these indicators is necessary but not sufficient to drive the primary outcomes). Overall, these basics are being well managed currently, but there remains an excessive focus on them, largely because of publically reported data and regulatory requirements. With a strong foundation, it is now time to focus on the more complex intermediate clinical outcomes—fluid management, infection control, diabetes management, medication management, and end-of-life care among others. Successfully addressing these intermediate outcomes will drive improvements in the primary outcomes, better survival, fewer hospitalizations, better patient experience with the treatment, and ultimately, improved quality of life. By articulating this view of quality in the ESRD program (pushing up the quality pyramid), the discussion about quality is reframed, and also, clinicians can better target their facilities in the direction of regulatory oversight and requirements about quality. Clinicians owe it to their patients, as the ESRD program celebrates its 40th anniversary, to rekindle the aspirations of the creators of the program, whose primary goal was to improve the lives of the patients afflicted with this devastating condition.

Use of Desmopressin Acetate in Severe Hyponatremia in the Intensive Care Unit

Rafat, Cédric — Thu, 21 Nov 2013 12:17:41 GMT-08:00

Intradialytic Hypotension and Risk of Cardiovascular Disease

Stefánsson, Bergur V. — Thu, 06 Nov 2014 06:42:34 GMT-08:00

Fluid Management: The Challenge of Defining Standards of Care

Flythe, Jennifer E. — Thu, 06 Nov 2014 06:42:34 GMT-08:00

Association of Left Ventricular Longitudinal Strain with Mortality among Stable Hemodialysis Patients with Preserved Left Ventricular Ejection Fraction

Liu, Yen-Wen — Thu, 23 May 2013 06:39:38 GMT-07:00

Time to Improve Fluid Management in Hemodialysis: Should We Abandon Clinical Assessment and Routinely Use Bioimpedance?

Covic, Adrian — Thu, 15 Aug 2013 07:48:54 GMT-07:00

Bioimpedance-Guided Fluid Management in Hemodialysis Patients

Moissl, Ulrich — Thu, 15 Aug 2013 07:48:55 GMT-07:00

Type 2 Translational Research for CKD

Tuttle, Katherine R. — Thu, 25 Apr 2013 08:56:42 GMT-07:00

Strategies to effectively treat people with CKD have been identified by conventional clinical research. Despite this evidence, awareness, screening, detection, diagnosis, risk factor control, treatment, and outcomes remain substandard. Translating clinical evidence into actionable measures that reduce the burden of CKD is a pressing need. Expansion from a “bench-to-bedside” paradigm (conventional type 1 translation) to research that encompasses “clinic and community” is the core concept of type 2 translation. Specifically, this is the discipline of identifying factors and using strategies that lead to adoption, maintenance, and sustainability of science-based interventions in practice. This review identifies key elements of type 2 translational research and highlights the current scope of this type of research for CKD. For type 2 translation to achieve the goals of providing high-quality care and better health outcomes, key facilitators (e.g., theory-based frameworks, adaptable interventions, and inclusion of sustainability and evaluation metrics) and essential elements (e.g., multidisciplinary team care, health information technology, and stakeholder engagement) must be integrated. The National Institute of Diabetes and Digestive and Kidney Diseases recently funded five proposals that aim to improve outcomes for people with CKD, focusing on diverse components of the healthcare continuum: patient safety and transitions; delivery of high-quality, evidence-based CKD care; and elimination of disparities. The need for type 2 translational research in CKD is urgent because of preventable human suffering and unsustainable costs of providing care. Focus on the theory, framework, and approaches we have suggested may help us meet that challenge.

Antiplatelet Therapy in the Management of Cardiovascular Disease in Patients with CKD: What Is the Evidence?

Jain, Nishank — Thu, 27 Sep 2012 12:51:56 GMT-07:00

Antiplatelet agents (APAs) are proven to reduce risk of major cardiovascular events in patients with cardiovascular disease and normal kidney function. With recent post hoc analyses of large trials questioning the safety and efficacy of APAs in CKD, major gaps exist in our understanding of platelet aggregability and the effects of APAs on thrombosis and bleeding in CKD. Clinical practice guidelines are ambiguous about use of such agents in CKD patients, because patients with moderate to advanced CKD were systematically excluded from clinical trials of APAs. CKD patients experience excessive rates of cardiovascular thrombotic events, yet paradoxically are at higher risk for major bleeding while receiving APAs. Furthermore, observational studies suggest that CKD patients may exhibit poor response to APAs. High residual platelet aggregability, as determined by inhibition of platelet aggregation, is associated with increased risk for cardiovascular events. In addition, metabolism of certain APAs may be altered in CKD patients. It is, therefore, imperative to explore the mechanisms responsible for poor response to APAs in CKD patients in order to use these drugs more safely and effectively. This review identifies the knowledge gaps and future trials needed to address those issues with the use of APAs in CKD patients.

Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

Lee, Timmy — Thu, 29 Aug 2013 12:30:42 GMT-07:00

Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.

Ongoing Clinical Trials in AKI

Faubel, Sarah — Thu, 22 Mar 2012 06:16:04 GMT-07:00

AKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with clinicaltrials.gov that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.

Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK Workshop on Trial Methodology

Palevsky, Paul M. — Thu, 22 Mar 2012 06:16:03 GMT-07:00

Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients’ health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled “Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers” in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

Obstetric Nephrology: Pregnancy in Women with Diabetic Nephropathy—The Role of Antihypertensive Treatment

Mathiesen, Elisabeth R. — Thu, 23 Aug 2012 10:13:11 GMT-07:00

This review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.

Obstetric Nephrology: AKI and Thrombotic Microangiopathies in Pregnancy

Fakhouri, Fadi — Thu, 09 Aug 2012 06:07:33 GMT-07:00

AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).

Early Start of Dialysis: A Critical Review

Rosansky, Steven — Mon, 09 May 2011 09:47:43 GMT-07:00

Prevention and Control of Phosphate Retention/Hyperphosphatemia in CKD-MBD: What Is Normal, When to Start, and How to Treat?

Martin, Kevin J. — Thu, 03 Feb 2011 07:44:55 GMT-08:00

Phosphate retention and, later, hyperphosphatemia are key contributors to chronic kidney disease (CKD)–mineral and bone disorder (MBD). Phosphate homeostatic mechanisms maintain normal phosphorus levels until late-stage CKD, because of early increases in parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Increased serum phosphorus, and these other mineral abnormalities, individually and collectively contribute to bone disease, vascular calcification, and cardiovascular disease. Earlier phosphate control may, therefore, help reduce the early clinical consequences of CKD-MBD, and help control hyperphosphatemia and secondary hyperparathyroidism in late-stage CKD. Indeed, it is now widely accepted that achieving normal phosphorus levels is associated with distinct clinical benefits. This therapeutic goal is achievable in CKD stages 3 to 5 but more difficult in dialysis patients. Currently, phosphate control is only initiated when hyperphosphatemia occurs, but a potentially beneficial and simple approach may be to intervene earlier, for example, when tubular phosphate reabsorption is substantially diminished. Early CKD-MBD management includes dietary phosphate restriction, phosphate binder therapy, and vitamin D supplementation. Directly treating phosphorus may be the most beneficial approach because this can reduce serum phosphorus, PTH, and FGF-23. This involves dietary measures, but these are not always sufficient, and it can be more effective to also consider phosphate binder use. Vitamin D sterols can improve vitamin D deficiency and PTH levels but may worsen phosphate retention and increase FGF-23 levels, and thus, may also require concomitant phosphate binder therapy. This article discusses when and how to optimize phosphate control to provide the best clinical outcomes in CKD-MBD patients.

Hemodialysis Treatment Time: A Fresh Perspective

Lacson, Eduardo — Thu, 01 Sep 2011 11:25:15 GMT-07:00

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental Glomerulosclerosis

McCarthy, Ellen T. — Thu, 21 Oct 2010 08:49:13 GMT-07:00

Circulating permeability factors may be important in idiopathic nephrotic syndrome (INS) including focal segmental glomerulosclerosis (FSGS) and in recurrence after renal transplantation. Evidence for plasma factors includes posttransplant recurrence of proteinuria and its response to plasmapheresis or immunoadsorption and induction of proteinuria in experimental animals by infusion of patient plasma or its fractions. The authors and other investigators have used proteomic techniques to seek pathogenic molecules. The authors have recently proposed cardiotrophin-like cytokine-1 (CLC-1) as an active factor in FSGS. Other potential permeability factors include hemopexin and vascular permeability factor in minimal change nephrotic syndrome (MCNS) and soluble urokinase receptor in FSGS. In the authors' studies, in vitro plasma permeability activity is blocked by diverse substances that may decrease levels of active molecules or block the effects of circulating permeability factors. It has been shown that the simple sugar galactose blocks the effect of FSGS serum on albumin permeability in vitro and decreases permeability activity when administered to patients. Because identities of permeability factors and their mechanisms of action are not well defined, therapy of INS/FSGS is empiric. Corticosteroids are the mainstay of initial therapy whereas calcineurin inhibitors such as cyclosporine A (CsA) and immunosuppressive medications provide adjunctive therapy. Nonspecific therapies such as blocking the renin-angiotensin system and controlling blood pressure and plasma lipids may also diminish proteinuria and slow progression. Identification of molecules that initiate proteinuria and application of findings from in vitro studies may lead to development of new treatments to arrest progression and prevent recurrence after transplantation.

The Spectrum of MYH9-Associated Nephropathy

Bostrom, Meredith A. — Thu, 18 Mar 2010 08:28:00 GMT-07:00

Causes of the excess incidence rates of chronic kidney disease in the African American population have long been under study. Recently, polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) have been associated with nondiabetic kidney diseases in African- and European-derived populations. Risk variants in MYH9 contribute to approximately 70% of nondiabetic forms of ESRD in African Americans and 40 to 45% of all ESRD in this ethnic group, with lesser effects in European Americans. It is clear that MYH9 polymorphisms have a significant impact on the incidence rates of kidney disease in African Americans. This article describes the current spectrum of biopsy-proven MYH9-associated kidney diseases, along with potential effects of MYH9 on ethnic differences in clinical outcome. MYH9 risk variants exhibit the most impressive association with any common complex kidney disease yet identified.

Control of Secondary Hyperparathyroidism by Vitamin D Receptor Agonists in Chronic Kidney Disease

Sprague, Stuart M. — Thu, 04 Feb 2010 09:20:21 GMT-08:00

Effective treatment options for managing secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) have advanced steadily since the early 1980s, from surgical removal of the parathyroid gland to pharmacologic intervention focused on reestablishing hormonal and mineral balances. In addition, earlier recognition of CKD via estimated GFR and educational efforts have led to advancements in diagnosis and treatment of elevated parathyroid hormone (PTH) and vitamin D deficiency. Clinical studies support the efficacy and safety of vitamin D receptor (VDR) agonists as effective treatments for SHPT. A number of considerations to ensure optimal SHPT control in CKD patients are apparent. VDR agonists effectively treat SHPT and vitamin D deficiency, but dosing needs to be optimized for each patient because the patient responds in an individualized manner to treatment to suppress and stabilize PTH levels. VDR agonist therapy should be continuous to ensure continued PTH suppression, coupled with strict monitoring of calcium and phosphorus to ensure compliance within target ranges. Awareness of the complex and beneficial effects of VDR agonists contributes to improved benefits in bone mineral disease and lower mortality risks.

Hepcidin for Clinicians

Young, Brian — Thu, 25 Jun 2009 08:16:47 GMT-07:00

Despite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.

Phosphate Levels and Cardiovascular Disease in the General Population

Foley, Robert N. — Thu, 07 May 2009 08:21:41 GMT-07:00

Phosphate levels are consistently linked with cardiac calcification, cardiovascular disease (CVD), and death in populations with chronic kidney disease. In addition, mechanistic insights suggest that phosphate levels that span the conventional normal range could lead to CVD. Examining these associations in the general population may be relevant because several interventions that may be suitable for primary or secondary prevention trials already exist. This review summarizes findings described from several community-based, prospective, observational studies. Graded associations with cardiac calcification, left ventricular hypertrophy, cardiovascular events, and death were evident, and cardiovascular risk seemed to accelerate with phosphate >3.5 to 4.0 mg/dl. Although the cause of these associations remains to be determined, several existing interventions may allow in-depth examination of the hypothesis that reducing phosphate levels could prevent CVD in the general population. Even as proof-of-concept trials and mechanistic studies are awaited, phosphate levels may be useful for cardiovascular risk stratification in adults without overt kidney disease.

Impact of Renal Failure on the Outcome of Dengue Viral Infection

Kuo, Mei-Chuan — Wed, 30 Jul 2008 11:41:41 GMT-07:00

Background and objectives: In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. Design, setting, participants, & measurements: A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. Results: From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. Conclusions: The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.

Interpreting Results of Clinical Trials: A Conceptual Framework

Singh, Ajay K. — Tue, 26 Aug 2008 10:01:51 GMT-07:00

Utility and Limitations of a Multicenter Nocturnal Home Hemodialysis Cohort

Pauly, Robert P. — Wed, 01 Oct 2008 11:43:18 GMT-07:00

Nocturnal home hemodialysis (NHD) is the most intensive dialysis strategy among dialytic renal replacement options and is receiving increased attention as more research reveals its physiologic restorative potential compared with conventional hemodialysis; however, a significant gap in knowledge remains concerning the predictors of program success and the clinical outcomes of NHD. This review aims to highlight the methodologic strengths and pitfalls of various study designs as they pertain to NHD research and lays the foundation for the CANandian Slow Long nightly ExtEnded dialysis Programs (CAN-SLEEP), a multicenter NHD research network aimed to facilitate investigation of NHD.

Commentary on Risks of Living Kidney Donation

Kestenbaum, Bryan R. — Mon, 11 Mar 2019 07:56:01 GMT-07:00

Correction

American Society of Nephrology — Mon, 18 Mar 2019 09:56:34 GMT-07:00

Dynamics of Organic Anion Transporter-Mediated Tubular Secretion during Postnatal Human Kidney Development and Maturation

Momper, Jeremiah D. — Mon, 18 Mar 2019 09:56:34 GMT-07:00

Complex Decision Making about Dialysis in Critically Ill Older Adults with AKI

Butler, Catherine R. — Thu, 21 Mar 2019 08:05:29 GMT-07:00

Prediction Models for AKI

Kwong, Yuenting Diana — Wed, 27 Mar 2019 07:03:06 GMT-07:00

Patient Perspective of Smartphone-Based Apps for CKD Self-Care

Rogers, Dale — Thu, 21 Mar 2019 08:05:30 GMT-07:00

Risks of Living Kidney Donation

Lentine, Krista L. — Mon, 11 Mar 2019 07:56:01 GMT-07:00

In the past decade, there have been increasing efforts to better define and quantify the short- and long-term risks of living kidney donation. Recent studies have expanded upon the previous literature by focusing on outcomes that are important to potential and previous donors, applying unique databases and/or registries to follow large cohorts of donors for longer periods of time, and comparing outcomes with healthy nondonor controls to estimate attributable risks of donation. Leading outcomes important to living kidney donors include kidney health, surgical risks, and psychosocial effects of donation. Recent data support that living donors may experience a small increased risk of severe CKD and ESKD compared with healthy nondonors. For most donors, the 15-year risk of kidney failure is <1%, but for certain populations, such as young, black men, this risk may be higher. New risk prediction tools that combine the effects of demographic and health factors, and innovations in genetic risk markers are improving kidney risk stratification. Minor perioperative complications occur in 10%–20% of donor nephrectomy cases, but major complications occur in <3%, and the risk of perioperative death is <0.03%. Generally, living kidney donors have similar or improved psychosocial outcomes, such as quality of life, after donation compared with before donation and compared with nondonors. Although the donation process should be financially neutral, living kidney donors may experience out-of-pocket expenses and lost wages that may or may not be completely covered through regional or national reimbursement programs, and may face difficulties arranging subsequent life and health insurance. Living kidney donors should be fully informed of the perioperative and long-term risks before making their decision to donate. Follow-up care allows for preventative care measures to mitigate risk and ongoing surveillance and reporting of donor outcomes to inform prior and future living kidney donors.

Recommendations for the Care of Patients Receiving Conservative Kidney Management

Davison, Sara N. — Thu, 28 Feb 2019 07:48:11 GMT-08:00

Conservative kidney management is increasingly accepted as an appropriate treatment option for patients with eGFR category 5 CKD who are unlikely to benefit from dialysis and/or who choose a nondialysis care option. However, there remains great variation in the delivery of their care. As part of the development of a conservative kidney management pathway that is undergoing evaluation, a set of recommendations specific to conservative kidney management for managing the complications of CKD and common symptoms was developed. These recommendations focus on the patient’s values and preferences and aim to optimize comfort and quality of life. Explanations for the interventions are provided to support the shared decision-making process between health care professionals, patients, and family members. The recommendations generally emphasize the preservation of function (cognitive, physical, and kidney) and address symptom burden, acknowledging that management priorities can change over time. The recommendations should be used in conjunction with other key elements of conservative kidney management, including clear communication and shared decision making for choosing conservative kidney management, advance care planning, and psychosocial support. Although there are limitations to the existing evidence specific to conservative kidney management, these recommendations are intended as a starting point toward reaching consensus and generating further evidence.

Estimation of Kidney Function in Oncology

Casal, Morgan A. — Tue, 19 Mar 2019 06:55:43 GMT-07:00

Estimation of kidney function in patients with cancer directly affects drug dosing, agent selection, and eligibility for clinical trials of novel agents. Overestimation of kidney function may lead to overdosing or inappropriate agent selection and corresponding toxicity. Conversely, underestimation of kidney function may lead to underdosing or inappropriate agent exclusion and subsequent therapeutic failure. It would seem obvious that the most accurate estimates of kidney function should be used to reduce variability in decision making and ultimately, the therapeutic outcomes of toxicity and clinical benefit. However, clinical decision making is often more complex. The Cockcroft–Gault formula remains the most universally implemented estimator of kidney function in patients with cancer, despite its relative inaccuracy compared with the Chronic Kidney Disease Epidemiology Collaboration equation. The Chronic Kidney Disease Epidemiology Collaboration equation is a more precise estimator of kidney function; however, many currently used kidney function cutoff values were determined before the development of the Chronic Kidney Disease Epidemiology Collaboration equation and creatinine assay standardization using Cockcroft–Gault estimates. There is a need for additional studies investigating the validity of currently used estimates of kidney function in patients with cancer and the applicability of traditional anticancer dosing and eligibility guidelines to modern and more accurate estimates of kidney function. In this review, we consider contemporary calculation methods used to estimate kidney function in patients with cancer. We discuss the clinical implications of using these various methods, including the potential influence on drug dosing, drug selection, and clinical trial eligibility, using carboplatin and cisplatin as case studies.

A Conceptual Framework of Palliative Care across the Continuum of Advanced Kidney Disease

Lam, Daniel Y. — Wed, 06 Feb 2019 07:08:09 GMT-08:00

Kidney palliative care is a growing discipline within nephrology. Kidney palliative care specifically addresses the stress and burden of advanced kidney disease through the provision of expert symptom management, caregiver support, and advance care planning with the goal of optimizing quality of life for patients and families. The integration of palliative care principles is necessary to address the multidimensional impact of advanced kidney disease on patients. In particular, patients with advanced kidney disease have a high symptom burden and experience greater intensity of care at the end of life compared with other chronic serious illnesses. Currently, access to kidney palliative care is lacking, whether delivered by trained kidney care professionals or by palliative care clinicians. These barriers include a gap in training and workforce, policies limiting access to hospice and outpatient palliative care services for patients with ESKD, resistance to integrating palliative care within the nephrology community, and the misconception that palliative care is synonymous with end-of-life care. As such, addressing kidney palliative care needs on a population level will require not only access to specialized kidney palliative care initiatives, but also equipping kidney care professionals with the skills to address basic kidney palliative care needs. This article will address the role of kidney palliative care for patients with advanced kidney disease, describe models of care including primary and specialty kidney palliative care, and outline strategies to improve kidney palliative care on a provider and system level.

Got CKD? There's an App for That!

Topf, Joel M. — Thu, 21 Mar 2019 08:05:30 GMT-07:00

Usability Testing of a Sick-Day Protocol in CKD

Doerfler, Rebecca M. — Wed, 13 Mar 2019 08:02:19 GMT-07:00

Estimated Glomerular Filtration Rate and the Risk of Cancer

Xu, Hong — Thu, 14 Mar 2019 06:59:51 GMT-07:00

Secondhand Smoke and CKD

Jhee, Jong Hyun — Thu, 07 Mar 2019 07:45:10 GMT-08:00

Rates of Cardiac Rhythm Abnormalities in Patients with CKD and Diabetes

Akoum, Nazem — Tue, 19 Mar 2019 06:55:45 GMT-07:00

Patients’ and Nephrologists’ Evaluation of Patient-Facing Smartphone Apps for CKD

Singh, Karandeep — Thu, 21 Mar 2019 08:05:30 GMT-07:00

A Prediction Model for Severe AKI in Critically Ill Adults That Incorporates Clinical and Biomarker Data

Bhatraju, Pavan Kumar — Wed, 27 Mar 2019 07:03:06 GMT-07:00

Selection and Receipt of Kidney Replacement in Critically Ill Older Patients with AKI

Bagshaw, Sean M. — Thu, 21 Mar 2019 08:05:29 GMT-07:00

Kidney Xenotransplantation

Shaw, Brian I. — Wed, 06 Feb 2019 07:08:08 GMT-08:00

Stopping RAS Inhibitors to Minimize AKI

Tomson, Charles — Wed, 27 Feb 2019 07:36:18 GMT-08:00

From Patient-Centered to Person-Centered Care for Kidney Diseases

Morton, Rachael L. — Wed, 27 Feb 2019 07:36:18 GMT-08:00

Management of the Hemodialysis Patient with Catheter-Related Bloodstream Infection

Farrington, Crystal A. — Tue, 05 Mar 2019 06:39:32 GMT-08:00

Frailty and Cognitive Deficits Limit Access to Kidney Transplantation

Harhay, Meera N. — Tue, 19 Mar 2019 06:55:45 GMT-07:00

Kidney Transplantation in a HIV-Positive Recipient

Sawinski, Deirdre — Mon, 18 Mar 2019 09:56:33 GMT-07:00

Subclinical Cognitive Impairment and Listing for Kidney Transplantation

Gupta, Aditi — Tue, 19 Mar 2019 06:55:44 GMT-07:00

Frailty and Access to Kidney Transplantation

Haugen, Christine E. — Tue, 19 Mar 2019 06:55:44 GMT-07:00

Etiology and Outcomes of Thrombotic Microangiopathies

Bayer, Guillaume — Tue, 12 Mar 2019 06:22:29 GMT-07:00

Authors’ Reply

Haddock, Bryan T. — Wed, 13 Feb 2019 06:28:49 GMT-08:00

The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells

Ignarski, Michael — Wed, 13 Mar 2019 08:05:07 GMT-07:00

Complementary Roles for Single-Nucleus and Single-Cell RNA Sequencing in Kidney Disease Research

O’Sullivan, Eoin D. — Wed, 13 Mar 2019 08:05:05 GMT-07:00

Renal Perfusion and Renal Nerve Activity

Lifschitz, Meyer D. — Wed, 13 Feb 2019 06:28:49 GMT-08:00

DNMT1 in Six2 Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development

Li, Szu-Yuan — Fri, 08 Mar 2019 01:16:28 GMT-08:00

Authors’ Reply

Wu, Haojia — Wed, 13 Mar 2019 08:05:06 GMT-07:00

Piecing Together the Risk of Sudden Cardiac Death on Dialysis

Weinhandl, Eric D. — Mon, 18 Mar 2019 09:03:42 GMT-07:00

Patient-Reported Outcomes: Toward Better Measurement of Patient-Centered Care in CKD

Wu, Albert W. — Thu, 21 Mar 2019 08:05:38 GMT-07:00

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study

Shroff, Rukshana — Thu, 07 Mar 2019 07:45:23 GMT-08:00

Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia

Zhang, Jie — Wed, 13 Mar 2019 08:05:06 GMT-07:00

Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis

Assimon, Magdalene M. — Mon, 18 Mar 2019 09:03:42 GMT-07:00

Improving CKD-Specific Patient-Reported Measures of Health-Related Quality of Life

Ware, John E. — Thu, 21 Mar 2019 08:05:39 GMT-07:00

Kidney Disease Quality of Life 36-Item Short Form Survey (KDQOL-36) Normative Values for the United States Dialysis Population and New Single Summary Score

Peipert, John D. — Thu, 21 Mar 2019 08:05:38 GMT-07:00

Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial

Block, Geoffrey A. — Thu, 07 Mar 2019 07:45:22 GMT-08:00

This Month's Highlights

American Society of Nephrology — Fri, 29 Mar 2019 10:00:27 GMT-07:00

LRG1 Promotes Diabetic Kidney Disease Progression by Enhancing TGF-β–Induced Angiogenesis

Hong, Quan — Mon, 11 Mar 2019 07:58:43 GMT-07:00

Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney Disease

Fu, Jia — Thu, 07 Mar 2019 07:45:22 GMT-08:00

The Other Glucose Transporter, SGLT1 – Also a Potential Trouble Maker in Diabetes?

Carlström, Mattias — Wed, 13 Mar 2019 08:05:05 GMT-07:00

Expanding the Patient’s Voice in Nephrology with Patient-Reported Outcomes

Peipert, John D. — Thu, 07 Mar 2019 07:45:22 GMT-08:00

You Are Just Now Telling Us About This? African American Perspectives of Testing for Genetic Susceptibility to Kidney Disease

Umeukeje, Ebele M. — Mon, 11 Mar 2019 07:58:42 GMT-07:00

Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens

Delville, Marianne — Fri, 08 Mar 2019 01:16:28 GMT-08:00

Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival

Aubert, Olivier — Thu, 14 Mar 2019 07:25:56 GMT-07:00

Requirements for Procedural Skills in Nephrology Training Programs

Norby, Suzanne M. — Fri, 15 Jun 2018 07:25:43 GMT-07:00

Training Nephrology Fellows in Temporary Hemodialysis Catheters and Kidney Biopsies Is Not Needed and Should Not Be Required

Shankland, Stuart J. — Fri, 15 Jun 2018 07:25:44 GMT-07:00

Kidney Biopsy Training and the Future of Nephrology

Brown, Robert S. — Fri, 15 Jun 2018 07:25:46 GMT-07:00

Mandating Staffing Ratios in Hemodialysis Facilities

Rastogi, Anjay — Wed, 06 Jun 2018 06:00:25 GMT-07:00

Burden of Proof for Tolvaptan in ADPKD

Mustafa, Reem A. — Fri, 13 Apr 2018 07:18:23 GMT-07:00

Training Nephrology Fellows in Temporary Hemodialysis Catheter Placement and Kidney Biopsies is Needed and Should be Required

Berns, Jeffrey S. — Fri, 15 Jun 2018 07:25:43 GMT-07:00

Contrast-Induced Acute Kidney Injury in the PRESERVE Trial

Siew, Edward D. — Thu, 19 Apr 2018 07:58:39 GMT-07:00

Trial Design Innovations to Accelerate Therapeutic Advances in Chronic Kidney Disease

Heerspink, Hiddo J.L. — Thu, 26 Apr 2018 06:24:14 GMT-07:00

Treatment of Depression in CKD Patients with an SSRI

Cukor, Daniel — Fri, 13 Apr 2018 07:18:23 GMT-07:00

Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence Report

Tucker, Bryan M. — Tue, 17 Oct 2017 06:48:10 GMT-07:00

A View of the Bundle from a Home Dialysis Perspective

Golper, Thomas A. — Mon, 18 Dec 2017 06:42:07 GMT-08:00

The Affordable Care Act, Medicaid Expansion, and Disparities in Kidney Disease

Trivedi, Amal N. — Thu, 14 Dec 2017 06:26:35 GMT-08:00

Striving to Achieve an Integrated Home Dialysis System

McCormick, Brendan B. — Thu, 14 Dec 2017 06:26:35 GMT-08:00

The Dialysis Facility Compare Five-Star Rating System at 2 Years

Pozniak, Alyssa — Mon, 18 Dec 2017 06:42:08 GMT-08:00

Integrated Care in ESKD

Brady, Brian M. — Tue, 29 Jan 2019 08:36:57 GMT-08:00

Integrated Care for People with Kidney Disease

Johnson, Douglas S. — Tue, 29 Jan 2019 08:36:57 GMT-08:00

Integrated Care in ESKD

Becker, Bryan N. — Tue, 29 Jan 2019 08:36:57 GMT-08:00

Urinary Potassium Excretion and Progression of CKD

Kim, Hyung Woo — Thu, 14 Feb 2019 05:53:09 GMT-08:00

Serum Metabolomic Alterations Associated with Proteinuria in CKD

Luo, Shengyuan — Thu, 07 Feb 2019 06:03:10 GMT-08:00

Hypernatremia

Qian, Qi — Wed, 06 Feb 2019 07:08:09 GMT-08:00

Complement Gene Variants and Shiga Toxin–Producing Escherichia coli–Associated Hemolytic Uremic Syndrome

Frémeaux-Bacchi, Véronique — Wed, 23 Jan 2019 05:42:18 GMT-08:00

MicroRNAs in AKI and Kidney Transplantation

Ledeganck, Kristien J. — Wed, 02 Jan 2019 07:01:12 GMT-08:00

MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation.

Are Generic Immunosuppressive Drugs the Solution for Providing Lifelong Medication Coverage to Transplant Recipients?

Potter, Lisa M. — Thu, 28 Feb 2019 07:48:11 GMT-08:00

Cost of Immunosuppressive Drugs and the Patient with a Kidney Transplant

Thomas, Cher — Thu, 28 Feb 2019 07:48:11 GMT-08:00

Secular Trends in the Cost of Immunosuppressants after Solid Organ Transplantation in the United States

Helmuth, Margaret E. — Thu, 28 Feb 2019 07:48:11 GMT-08:00

Cultivating a Research-Ready Dialysis Community

Flythe, Jennifer E. — Fri, 08 Feb 2019 05:19:08 GMT-08:00

Staying the Course: Through End of Life in ESRD

Perry, Erica — Tue, 19 Feb 2019 06:47:10 GMT-08:00

Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney Transplant

Au, Eric H. — Thu, 14 Feb 2019 06:15:05 GMT-08:00

Background Patients with ESRD have a substantially increased cancer risk, but few studies have examined the patterns of cancer mortality along a patient's journey from dialysis to transplantation.

The Case for a Bariatric-Centered Approach to CKD Care

Friedman, Allon N. — Thu, 10 Jan 2019 12:47:19 GMT-08:00

Mentorship in the Digital Age

Shah, Silvi — Tue, 15 Jan 2019 05:33:01 GMT-08:00

Patient Entrepreneurs to Drive Health Care Innovation for Kidney Disease

Hehenberger, Karin — Mon, 21 Jan 2019 07:45:33 GMT-08:00

Assessment and Management of Hypertension among Patients on Peritoneal Dialysis

Vaios, Vasilios — Fri, 19 Oct 2018 08:18:09 GMT-07:00

Approximately 7%–10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.

Patients,’ Nephrologists,’ and Predicted Estimations of ESKD Risk Compared with 2-Year Incidence of ESKD

Potok, O. Alison — Thu, 10 Jan 2019 12:47:20 GMT-08:00

Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD

Bathini, Lavanya — Thu, 10 Jan 2019 12:47:20 GMT-08:00

Incidence and Risk Factors of Early Onset Neonatal AKI

Charlton, Jennifer R. — Thu, 31 Jan 2019 09:00:35 GMT-08:00

Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka

Anand, Shuchi — Fri, 18 Jan 2019 08:36:27 GMT-08:00

Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis

Lin, Eugene — Thu, 03 Jan 2019 08:29:50 GMT-08:00

Kir4.1/Kir5.1 Activity Is Essential for Dietary Sodium Intake–Induced Modulation of Na-Cl Cotransporter

Wu, Peng — Mon, 17 Dec 2018 07:27:16 GMT-08:00

New Insights into the Mechanism of NO3- Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein Family

Lagostena, Laura — Fri, 11 Jan 2019 09:16:33 GMT-08:00

Producing Purer Podocytes

Freedman, Benjamin S. — Fri, 11 Jan 2019 09:16:34 GMT-08:00

Readmissions Metrics in Hemodialysis: Do the Specifics Matter?

Dad, Taimur — Thu, 03 Jan 2019 08:29:50 GMT-08:00

Activation and Proliferation of PD-1+ Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-2

Sadasivam, Mohanraj — Tue, 08 Jan 2019 07:41:33 GMT-08:00

IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice

Wada, Yukihiro — Tue, 08 Jan 2019 07:41:33 GMT-08:00

This Month’s Highlights

American Society of Nephrology — Thu, 31 Jan 2019 10:00:30 GMT-08:00

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population

Gilbertson, David T. — Thu, 24 Jan 2019 06:22:31 GMT-08:00

Hepatocyte Growth Factor–Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD

Oka, Masatoshi — Fri, 11 Jan 2019 09:16:34 GMT-08:00

Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells

Yoshimura, Yasuhiro — Fri, 11 Jan 2019 09:16:35 GMT-08:00

Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16A

Schreiber, Rainer — Thu, 03 Jan 2019 08:29:51 GMT-08:00

Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities

Estrada, Chelsea C. — Mon, 14 Jan 2019 08:13:21 GMT-08:00

Inhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of this pathway. We also review the renal effects of VEGF inhibition’s mediation of key downstream signaling pathways, specifically MAPK/ERK1/2, endothelial nitric oxide synthase, and mammalian target of rapamycin (mTOR). Direct VEGFA inhibition via antibody binding or VEGF trap (a soluble decoy receptor) is associated with renal-specific thrombotic microangiopathy (TMA). Reports also indicate that tyrosine kinase inhibition of the VEGF receptors is preferentially associated with glomerulopathies such as minimal change disease and FSGS. Inhibition of the downstream pathway RAF/MAPK/ERK has largely been associated with tubulointerstitial injury. Inhibition of mTOR is most commonly associated with albuminuria and podocyte injury, but has also been linked to renal-specific TMA. In all, we review the experimentally validated mechanisms by which VEGFA-VEGFR2 inhibitors contribute to nephrotoxicity, as well as the wide range of clinical manifestations that have been reported with their use. We also highlight potential avenues for future research to elucidate mechanisms for minimizing nephrotoxicity while maintaining therapeutic efficacy.

A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation

Marques, Igor Denizarde Bacelar — Thu, 03 Jan 2019 08:29:51 GMT-08:00

Frailty and Changes in Cognitive Function after Kidney Transplantation

Chu, Nadia M. — Thu, 24 Jan 2019 06:22:32 GMT-08:00

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients

Mann, Nina — Thu, 17 Jan 2019 11:46:29 GMT-08:00

Women in Nephrology Today

Lederer, Eleanor — Mon, 22 Oct 2018 07:26:58 GMT-07:00

The New HHS Kidney Innovation Accelerator

Fowler, Kevin John — Thu, 25 Oct 2018 11:00:08 GMT-07:00

The Kidney Accelerator

Watnick, Suzanne — Thu, 25 Oct 2018 11:00:08 GMT-07:00

Extracorporeal Removal of Light Chains

Finkel, Kevin W. — Mon, 22 Oct 2018 07:26:59 GMT-07:00

Persistent Bias: A Threat to Diversity among Health Care Leaders

Crews, Deidra C. — Tue, 07 Aug 2018 08:07:06 GMT-07:00

Inclusion of Phosphorus in the Nutrition Facts Label

Borgi, Lea — Fri, 30 Nov 2018 06:20:11 GMT-08:00

Plant-Based Diets in CKD

Clegg, Deborah J. — Wed, 26 Dec 2018 11:00:42 GMT-08:00

Kidneys on Chips

Yeung, Catherine K. — Mon, 01 Oct 2018 08:12:25 GMT-07:00

Timing of Kidney Replacement Therapy in Acute Kidney Injury

Zarbock, Alexander — Fri, 30 Nov 2018 06:20:11 GMT-08:00

Blood Pressure Goals in Patients with CKD

Chang, Alex R. — Mon, 19 Nov 2018 07:17:42 GMT-08:00

Hypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4–5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.

Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

de Jong, Maarten A. — Mon, 17 Dec 2018 07:27:02 GMT-08:00

Variability of Two Metabolomic Platforms in CKD

Rhee, Eugene P. — Thu, 20 Dec 2018 08:52:58 GMT-08:00

Patterns of Beverages Consumed and Risk of Incident Kidney Disease

Rebholz, Casey M. — Thu, 27 Dec 2018 07:36:18 GMT-08:00

Effects of Molidustat in the Treatment of Anemia in CKD

Macdougall, Iain C. — Mon, 17 Dec 2018 07:27:01 GMT-08:00

Effects of the Potassium-Binding Polymer Patiromer on Markers of Mineral Metabolism

Bushinsky, David A. — Wed, 31 Oct 2018 10:53:46 GMT-07:00

Population-Based Study of Risk of AKI with Levetiracetam

Yau, Kevin — Tue, 11 Dec 2018 08:43:42 GMT-08:00

Screening Transplant Waitlist Candidates for Coronary Artery Disease

Gill, John S. — Fri, 28 Dec 2018 08:27:50 GMT-08:00

The Quality of Reporting of Kidney Research: A Challenge to JASN

Briggs, Josephine P. — Thu, 13 Dec 2018 10:20:19 GMT-08:00

The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling

Andrikopoulos, Petros — Mon, 10 Dec 2018 08:13:36 GMT-08:00

DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation

Wanner, Nicola — Wed, 05 Dec 2018 06:49:23 GMT-08:00

Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis

Mukherjee, Malini — Tue, 04 Dec 2018 10:57:43 GMT-08:00

Survival among Veterans Obtaining Dialysis in VA and Non-VA Settings

Wang, Virginia — Fri, 07 Dec 2018 04:11:08 GMT-08:00

Morphological Processes of Foot Process Effacement in Puromycin Aminonucleoside Nephrosis Revealed by FIB/SEM Tomography

Ichimura, Koichiro — Tue, 04 Dec 2018 10:57:43 GMT-08:00

Growth of the ESKD Population: Progress or Peril?

Collins, Allan J. — Mon, 17 Dec 2018 07:27:17 GMT-08:00

Sex-Related Disparities in CKD Progression

Ricardo, Ana C. — Mon, 03 Dec 2018 07:33:16 GMT-08:00

Nucleophosmin Phosphorylation as a Diagnostic and Therapeutic Target for Ischemic AKI

Wang, Zhiyong — Thu, 20 Dec 2018 06:45:08 GMT-08:00

Background Ischemic AKI lacks a urinary marker for early diagnosis and an effective therapy. Differential nucleophosmin (NPM) phosphorylation is a potential early marker of ischemic renal cell injury and a therapeutic target. Methods Differential NPM phosphorylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithelial cells, fresh kidney tissue, and urine before and after ischemic injury. The biologic behavior and toxicity of NPM was assessed using phospho-NPM mutant proteins that either mimic stress-induced or normal NPM phosphorylation. Peptides designed to interfere with NPM function were used to explore NPM as a therapeutic target. Results Within hours of stress, virtually identical phosphorylation changes were detected at distinct serine/threonine sites in NPM harvested from primary renal cells, tissue, and urine. A phosphomimic NPM protein that replicated phosphorylation under stress localized to the cytosol, formed monomers that interacted with Bax, a cell death protein, coaccumulated with Bax in isolated mitochondria, and significantly increased cell death after stress; wild-type NPM or a phosphomimic NPM with a normal phosphorylation configuration did not. Three renal targeted peptides designed to interfere with NPM at distinct functional sites significantly protected against cell death, and a single dose of one peptide administered several hours after ischemia that would be lethal in untreated mice significantly reduced AKI severity and improved survival. Conclusions These findings establish phosphorylated NPM as a potential early marker of ischemic AKI that links early diagnosis with effective therapeutic interventions.

Postoperative AKI—Prevention Is Better than Cure?

Bell, Samira — Tue, 18 Dec 2018 04:10:46 GMT-08:00

Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients

Findlay, Mark Duncan — Fri, 07 Dec 2018 04:11:09 GMT-08:00

Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation

Park, Sehoon — Tue, 18 Dec 2018 04:10:47 GMT-08:00

Projecting ESRD Incidence and Prevalence in the United States through 2030

McCullough, Keith P. — Mon, 17 Dec 2018 07:27:15 GMT-08:00

Expression Profiling of Fibroblasts in Chronic and Acute Disease Models Reveals Novel Pathways in Kidney Fibrosis

Higashi, Atsuko Y. — Thu, 13 Dec 2018 10:20:20 GMT-08:00

Improving Clinical Outcomes in the Era of Information Ubiquity

Califf, Robert M. — Thu, 20 Dec 2018 06:45:07 GMT-08:00

Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis

Wu, Haojia — Mon, 03 Dec 2018 07:33:15 GMT-08:00

Quantity and Reporting Quality of Kidney Research

Chatzimanouil, Markos Kyriakos Tomidis — Thu, 13 Dec 2018 10:20:19 GMT-08:00

Intravenous Fluids

Palevsky, Paul M. — Tue, 06 Nov 2018 08:25:14 GMT-08:00

Renal Fellow Network

Farouk, Samira — Fri, 14 Sep 2018 07:12:57 GMT-07:00

Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKD

Yamamoto, Ryohei — Thu, 15 Nov 2018 07:47:59 GMT-08:00

Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni Indians

Nelson, Robert G. — Thu, 15 Nov 2018 07:47:59 GMT-08:00

Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans

Burwick, Nicholas — Thu, 15 Nov 2018 07:48:00 GMT-08:00

PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT

Ginsberg, Charles — Tue, 13 Nov 2018 05:46:39 GMT-08:00

BK Virus Nephropathy

Sawinski, Deirdre — Fri, 21 Sep 2018 06:27:12 GMT-07:00

Lung Ultrasonography in the Acutely Dyspneic Hemodialysis Patient

Ross, Daniel W. — Wed, 17 Oct 2018 08:58:13 GMT-07:00

Addressing Disparities in Living Donor Kidney Transplantation

Lentine, Krista L. — Wed, 14 Nov 2018 07:21:55 GMT-08:00

Helping More Patients Receive a Living Donor Kidney Transplant

Garg, Amit X. — Mon, 06 Aug 2018 05:55:05 GMT-07:00

The best treatment option for many patients with kidney failure is a kidney transplant from a living donor. Countries that successfully increase their rate of living kidney donation will decrease their reliance on dialysis, the most expensive and high-risk form of kidney replacement therapy. Outlined here are some barriers that prevent some patients from pursuing living kidney donation and current knowledge on some potential solutions to these barriers. Also described are strategies to promote living kidney donation in a defensible system of practice. Safely increasing the rate of living kidney donation will require better programs and policies to improve the experiences of living donors and their recipients, to safeguard the practice for years to come.

Acute Kidney Injury among Hospitalized Children in China

Xu, Xin — Thu, 04 Oct 2018 06:09:52 GMT-07:00

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome

Wang, Chia-shi — Thu, 15 Nov 2018 07:48:00 GMT-08:00

Duration of Treatment with Corticosteroids and Recovery of Kidney Function in Acute Interstitial Nephritis

Fernandez-Juarez, Gema — Mon, 05 Nov 2018 09:59:01 GMT-08:00

The Terrible Toll of the Kidney Shortage

McCormick, Frank — Mon, 12 Nov 2018 08:03:51 GMT-08:00

Authors’ Reply

Sethi, Sanjeev — Fri, 02 Nov 2018 05:06:10 GMT-07:00

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Ide, Shintaro — Tue, 30 Oct 2018 07:39:27 GMT-07:00

A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation

Monteiro, Maria B. — Thu, 25 Oct 2018 11:00:10 GMT-07:00

Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort Study

Przech, Sebastian — Wed, 07 Nov 2018 09:13:02 GMT-08:00

Genetic Analysis of 400 Patients Refines Understanding and Implicates a New Gene in Atypical Hemolytic Uremic Syndrome

Bu, Fengxiao — Tue, 30 Oct 2018 07:39:26 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 30 Nov 2018 01:00:21 GMT-08:00

Smoldering Myeloma Presenting with Renal Histopathology of Monoclonal Gammopathy of Renal Significance: Adding to the Complexity

Kousios, Andreas — Tue, 30 Oct 2018 07:39:28 GMT-07:00

Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry Disease

Lenders, Malte — Thu, 01 Nov 2018 09:09:02 GMT-07:00

Cardiovascular Events after New-Onset Atrial Fibrillation in Adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) Study

Bansal, Nisha — Tue, 30 Oct 2018 07:39:27 GMT-07:00

Health Outcome Priorities of Older Adults with Advanced CKD and Concordance with Their Nephrology Providers’ Perceptions

Ramer, Sarah J. — Thu, 01 Nov 2018 09:09:02 GMT-07:00

Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age

Zheng, Wenling — Mon, 12 Nov 2018 08:03:52 GMT-08:00

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial

Saglimbene, Valeria — Mon, 12 Nov 2018 08:03:52 GMT-08:00

Are Current Strategies for Building a Human Kidney Misguided? Speculative Alternatives

Fine, Leon G. — Tue, 30 Oct 2018 07:39:28 GMT-07:00

Persistent Underrepresentation of Kidney Disease in Randomized, Controlled Trials of Cardiovascular Disease in the Contemporary Era

Maini, Rohit — Fri, 02 Nov 2018 05:06:09 GMT-07:00

Evaluating the Evidence behind Policy Mandates in US Dialysis Care

Erickson, Kevin F. — Fri, 02 Nov 2018 05:06:10 GMT-07:00

Anticoagulant-Related Nephropathy

Brodsky, Sergey — Mon, 12 Nov 2018 08:03:52 GMT-08:00

Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of “renal events” described in the post hoc analyses of three pivotal anticoagulation trials and three retrospective analyses of large clinical databases. Taken together, these analyses suggest that ARN is not a rare occurrence in the anticoagulated patient with atrial fibrillation. However, much work needs to be done to understand the condition, particularly prospective studies, to avoid the biases inherent in post hoc and retrospective analyses. Finally, we provide recommendations regarding the diagnosis and management of ARN on the basis of the best information available.

Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease

Chebib, Fouad T. — Thu, 26 Jul 2018 06:21:31 GMT-07:00

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.

CKD in Patients with Bilateral Oophorectomy

Kattah, Andrea G. — Wed, 19 Sep 2018 07:31:58 GMT-07:00

End-Stage Kidney Disease following Surgical Management of Kidney Cancer

Ellis, Robert J. — Fri, 28 Sep 2018 05:26:41 GMT-07:00

Patient Experience with Primary Care Physician and Risk for Hospitalization in Hispanics with CKD

Cedillo-Couvert, Esteban A. — Thu, 18 Oct 2018 07:16:25 GMT-07:00

Kidney Biopsy–Related Complications in Hospitalized Patients with Acute Kidney Disease

Moledina, Dennis G. — Mon, 22 Oct 2018 07:27:00 GMT-07:00

Hepatitis C Virus Infection in ESKD Patients

Ladino, Marco — Tue, 31 Jul 2018 06:31:28 GMT-07:00

The Patient Receiving Automated Peritoneal Dialysis with Volume Overload

Trinh, Emilie — Mon, 10 Sep 2018 04:48:34 GMT-07:00

Acute Kidney Injury in Children with Kidney Transplantation

Alkandari, Omar — Fri, 21 Sep 2018 06:27:14 GMT-07:00

Regulatory T Cells and Kidney Transplantation

Martin-Moreno, Paloma Leticia — Tue, 22 May 2018 06:32:31 GMT-07:00

The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.

Maintenance of Certification

Weinstein, Adam — Tue, 10 Oct 2017 07:48:57 GMT-07:00

Maintenance of Certification

Rosner, Mitchell H. — Tue, 10 Oct 2017 07:48:57 GMT-07:00

Coaching Nephrology Trainees Who Struggle with Clinical Performance

Warburton, Karen M. — Wed, 01 Nov 2017 06:17:31 GMT-07:00

Transformation of ABIM and What the Changes Mean to Nephrologists

Ikizler, T. Alp — Tue, 10 Oct 2017 07:48:57 GMT-07:00

TESTING Corticosteroids in IgA Nephropathy

Tam, Frederick W.K. — Wed, 13 Dec 2017 07:16:50 GMT-08:00

SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts

Wei, Chengguo — Fri, 19 Oct 2018 08:18:17 GMT-07:00

Authors’ Reply

Ishida, Julie H. — Fri, 21 Sep 2018 06:27:41 GMT-07:00

Gabepentinoids and Benzodiazepines in Medicare Part D

Weinhandl, Eric D. — Fri, 21 Sep 2018 06:27:41 GMT-07:00

Peroxidasin—a Novel Autoantigen in Anti-GBM Disease?

McAdoo, Stephen P. — Fri, 12 Oct 2018 07:42:18 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Wed, 31 Oct 2018 01:00:28 GMT-07:00

The Science of Fistula Maturation

Oliver, Matthew J. — Wed, 10 Oct 2018 09:16:33 GMT-07:00

Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of Atherosclerosis

Bhatraju, Pavan K. — Thu, 04 Oct 2018 06:10:07 GMT-07:00

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS

Trachtman, Howard — Thu, 25 Oct 2018 09:30:09 GMT-07:00

Broadening Our Perspectives: CKD Care and the Dialysis Transition

Hostetter, Thomas — Wed, 10 Oct 2018 09:16:32 GMT-07:00

Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes

McCall, A. Scott — Tue, 02 Oct 2018 07:26:26 GMT-07:00

Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway

Cornelius, Ryan J. — Tue, 09 Oct 2018 09:11:18 GMT-07:00

Combined Structural and Functional Imaging of the Kidney Reveals Major Axial Differences in Proximal Tubule Endocytosis

Schuh, Claus D. — Tue, 09 Oct 2018 09:11:19 GMT-07:00

Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2–Mediated Water Homeostasis

Li, Suchun — Wed, 10 Oct 2018 09:16:33 GMT-07:00

Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation Study

Robbin, Michelle L. — Thu, 11 Oct 2018 05:54:44 GMT-07:00

Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss

Zewinger, Stephen — Tue, 02 Oct 2018 07:26:26 GMT-07:00

Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial

Wanner, Christoph — Fri, 12 Oct 2018 07:42:18 GMT-07:00

Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy

Zhang, Yang — Fri, 19 Oct 2018 08:18:18 GMT-07:00

Savings Opportunity from Improved CKD Care Management

Liu, Harry H. — Tue, 02 Oct 2018 07:26:27 GMT-07:00

Translational Methods in Nephrology: Individual Treatment Effect Modeling

Wilson, F. Perry — Tue, 02 Oct 2018 07:26:26 GMT-07:00

Addressing Financial Disincentives to Improve CKD Care

Berns, Jeffrey S. — Wed, 10 Oct 2018 09:16:33 GMT-07:00

Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Shafi, Tariq — Wed, 15 Aug 2018 07:23:59 GMT-07:00

The ABCs in the Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Wanner, Christoph — Wed, 15 Aug 2018 07:23:59 GMT-07:00

Telehealth and Home Dialysis

Bieber, Scott D. — Tue, 24 Jul 2018 01:47:05 GMT-07:00

Rebuilding the Pipeline of Investigators in Nephrology Research in the United States

Norton, Jenna M. — Tue, 17 Jul 2018 05:20:17 GMT-07:00

Urgent Start Peritoneal Dialysis

Blake, Peter G. — Tue, 17 Jul 2018 05:20:16 GMT-07:00

Organ Donation and the Principles of Gift Law

Glazier, Alexandra K. — Tue, 17 Jul 2018 05:20:17 GMT-07:00

Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Zoccali, Carmine — Wed, 15 Aug 2018 07:23:59 GMT-07:00

Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Bansal, Nisha — Wed, 15 Aug 2018 07:23:59 GMT-07:00

Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Winkelmayer, Wolfgang C. — Wed, 15 Aug 2018 07:23:58 GMT-07:00

Genetic Contribution to Risk for Diabetic Kidney Disease

Rich, Stephen S. — Mon, 16 Jul 2018 07:44:51 GMT-07:00

Urgent: Stop Preventable Infections Now

Collins, Allan J. — Thu, 22 Mar 2018 05:49:23 GMT-07:00

100% Use of Infection Control Procedures in Hemodialysis Facilities

Vijayan, Anitha — Thu, 22 Mar 2018 05:49:24 GMT-07:00

What We Learned from Ebola

Boyce, John M. — Thu, 22 Mar 2018 05:49:23 GMT-07:00

Addressing the Problem of Multidrug-Resistant Organisms in Dialysis

D’Agata, Erika M.C. — Thu, 22 Mar 2018 05:49:23 GMT-07:00

Treatment Choices for Hepatitis C in Patients with Kidney Disease

Fabrizi, Fabrizio — Fri, 09 Mar 2018 06:45:08 GMT-08:00

Chimeric Antigen Receptor T Cell Therapy and the Kidney

Jhaveri, Kenar D. — Fri, 09 Mar 2018 06:45:08 GMT-08:00

Chronic Kidney Disease in India

Varughese, Santosh — Tue, 30 Jan 2018 07:17:34 GMT-08:00

Protecting Donors and Safeguarding Altruism in the United States

Wiseman, Alexander C. — Fri, 09 Mar 2018 06:45:08 GMT-08:00

Nephrology at a Crossroads

de Boer, Ian H. — Thu, 11 Jan 2018 11:50:00 GMT-08:00

Effects of Diabetes Medications Targeting the Incretin System on the Kidney

MacIsaac, Richard J. — Wed, 10 Jan 2018 06:47:57 GMT-08:00

Burnout in Nephrology

Roberts, John K. — Thu, 11 Jan 2018 11:50:00 GMT-08:00

Addressing Physician Burnout

Williams, Amy W. — Thu, 11 Jan 2018 11:50:00 GMT-08:00

Are SGLT2 Inhibitors Ready for Prime Time for CKD?

Pecoits-Filho, Roberto — Mon, 11 Sep 2017 07:49:29 GMT-07:00

Transforming Nephrology

Rosner, Mitchell H. — Thu, 04 May 2017 01:22:15 GMT-07:00

Ultrafiltration Therapy for Heart Failure: Balancing Likely Benefits against Possible Risks

Kazory, Amir — Thu, 31 Mar 2016 06:46:06 GMT-07:00

Heart failure remains a major public health concern because of its high prevalence, morbidity, mortality, and financial burden. The poor clinical outcomes associated with acute decompensated heart failure, suboptimal efficacy and safety profile of conventional treatment regimens, and unsatisfactory experiences with the newer classes of pharmacologic therapy underlie the interest in the use of extracorporeal isolated ultrafiltration in this setting. In this article, selected mechanistic aspects of ultrafiltration therapy are briefly reviewed followed by a critical overview of the largest trials in this field. I will discuss the clinical relevance of renal dysfunction and decongestion as two commonly used end points of safety and efficacy in the ultrafiltration trials, with emphasis on the emerging pertinent notions that could challenge our conventional thinking. Finally, a number of practical recommendations (e.g., customization of ultrafiltration rates) are provided for ultrafiltration therapy in the setting of acute decompensated heart failure. Because of a paucity of evidence, universally accepted consensus guidelines cannot yet be generated. As such, when considering ultrafiltration therapy for acute decompensated heart failure, the likely benefits should be carefully balanced against the potential risks for an individual patient. A conceivable implication of the ultrafiltration trials is that collaborative heart failure programs benefiting from nephrology expertise and resources could improve the outcomes and reduce the cost.

Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans

Ma, Jun — Thu, 19 May 2016 06:54:29 GMT-07:00

Health Education and General Practitioner Training in Hypertension Management: Long-Term Effects on Kidney Function

Jafar, Tazeen H. — Thu, 19 May 2016 06:54:27 GMT-07:00

Anxiety in Patients Treated with Hemodialysis

Cohen, Scott D. — Thu, 22 Sep 2016 06:35:07 GMT-07:00

Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients’ perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD.

Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?

Friedman, Allon N. — Thu, 08 Oct 2015 09:09:45 GMT-07:00

Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease.

Insights into the Role of Mucosal Immunity in IgA Nephropathy

Zhang, Yue-miao — Tue, 31 Jul 2018 06:31:27 GMT-07:00

Defining Hypertension

Toto, Robert D. — Fri, 21 Sep 2018 06:27:13 GMT-07:00

Intensive Blood Pressure Targets and Kidney Disease

Chang, Tara I. — Thu, 24 May 2018 06:17:07 GMT-07:00

Target Blood Pressure for Cardiovascular Disease Prevention in Patients with CKD

Chang, Alex R. — Thu, 24 May 2018 06:17:07 GMT-07:00

Clinical Pharmacogenomics

Adams, Solomon M. — Wed, 23 May 2018 06:45:21 GMT-07:00

Pharmacogenomics is a tool for practitioners to provide precision pharmacotherapy using genomics. All providers are likely to encounter genomic data in practice with the expectation that they are able to successfully apply it to patient care. Pharmacogenomics tests for genetic variations in genes that are responsible for drug metabolism, transport, and targets of drug action. Variations can increase the risk for drug toxicity or poor efficacy. Pharmacogenomics can, therefore, be used to help select the best medication or aid in dosing. Nephrologists routinely treat cardiovascular disease and manage patients after kidney transplantation, two situations for which there are several high-evidence clinical recommendations for commonly used anticoagulants, antiplatelets, statins, and transplant medications. Successful use of pharmacogenomics in practice requires that providers are familiar with how to access and use pharmacogenomics resources. Similarly, clinical decision making related to whether to use existing data, whether to order testing, and if data should be used in practice is needed to deliver precision medicine. Pharmacogenomics is applicable to virtually every medical specialty, and nephrologists are well positioned to be implementation leaders.

Nephrotoxicity and Chinese Herbal Medicine

Yang, Bo — Tue, 03 Apr 2018 06:06:03 GMT-07:00

Chinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening.

Microbiome and Cardiovascular Disease in CKD

Jovanovich, Anna — Wed, 09 May 2018 06:55:46 GMT-07:00

Patients with CKD exhibit a disproportionate burden of cardiovascular mortality, which likely stems from the presence of unique, nontraditional risk factors that accompany deteriorating kidney function. Mounting evidence suggests that alterations to the intestinal microbiome in CKD may serve as one such risk factor. The human intestinal tract is home to >100 trillion micro-organisms made up of a collection of commensal, symbiotic, and pathogenic species. These species along with their local environment constitute the intestinal microbiome. Patients with CKD show intestinal dysbiosis, an alteration of the gut micro-organism composition and function. Recent evidence links byproducts of intestinal dysbiosis to vascular calcification, atherosclerosis formation, and adverse cardiovascular outcomes in CKD. CKD-associated intestinal dysbiosis may also be accompanied by defects in intestinal barrier function, which could further enhance the negative effects of pathogenic intestinal bacteria in the human host. Thus, intestinal dysbiosis, defective intestinal barrier function, and a reduced capacity for clearance by the kidney of absorbed bacterial byproducts may all potentiate the development of cardiovascular disease in CKD. This narrative review focuses on microbiome-mediated mechanisms associated with CKD that may promote atherosclerosis formation and cardiovascular disease. It includes (1) new data supporting the hypothesis that intestinal barrier dysfunction leads to bacterial translocation and endotoxemia that potentiate systemic inflammation, (2) information on the accumulation of dietary-derived bacterial byproducts that stimulate pathways promoting atheromatous changes in arteries and cardiovascular disease, and (3) potential interventions. Despite great scientific interest in and a rapidly growing body of literature on the relationship between the microbiome and cardiovascular disease in CKD, many important questions remain unanswered.

Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection

Tartof, Sara Yee — Fri, 21 Sep 2018 06:27:12 GMT-07:00

Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD

Kendrick, Jessica — Thu, 20 Sep 2018 09:05:12 GMT-07:00

Protein Energy Wasting in Hemodialysis Patients

Sarav, Menaka — Thu, 28 Jun 2018 06:16:44 GMT-07:00

Claudin-14 Gene Polymorphisms and Urine Calcium Excretion

Arcidiacono, Teresa — Wed, 19 Sep 2018 07:31:56 GMT-07:00

Impact of Navigators on First Visit to a Transplant Center, Waitlisting, and Kidney Transplantation

Sullivan, Catherine M. — Wed, 22 Aug 2018 07:40:12 GMT-07:00

Minding the Missing Link

Vinson, Amanda J. — Wed, 25 Jul 2018 10:04:31 GMT-07:00

Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis

Gomez Mendez, Liliana Michelle — Wed, 08 Aug 2018 09:28:22 GMT-07:00

Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease

Guo, Yiqing — Fri, 24 Aug 2018 05:40:27 GMT-07:00

Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney Disease

Zhou, Chenchen — Thu, 09 Aug 2018 09:22:51 GMT-07:00

Fibroblast Growth Factor-23 Is Not a Single Bystander in Chronic Kidney Disease Mortality

Pelletier, Solenne — Fri, 13 Jul 2018 12:30:03 GMT-07:00

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise

Haddock, Bryan Thomas — Tue, 11 Sep 2018 07:32:46 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 28 Sep 2018 01:00:27 GMT-07:00

Authors’ Reply

Herrington, William G. — Fri, 13 Jul 2018 12:30:04 GMT-07:00

Human-Specific Abnormal Alternative Splicing of Wild-Type PKD1 Induces Premature Termination of Polycystin-1

Lea, Wendy A. — Wed, 05 Sep 2018 07:37:45 GMT-07:00

Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort Study

Suarez, Jonathan — Fri, 17 Aug 2018 06:31:17 GMT-07:00

Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial Kidney Disease

Chan, Siu Chiu — Fri, 10 Aug 2018 05:49:35 GMT-07:00

Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease

Cassini, Marcelo F. — Wed, 12 Sep 2018 11:25:23 GMT-07:00

Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to TAMs in Cancer?

Weimbs, Thomas — Wed, 12 Sep 2018 11:25:22 GMT-07:00

Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing

Lanktree, Matthew B. — Wed, 22 Aug 2018 07:40:32 GMT-07:00

The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney Disease

Eriguchi, Masahiro — Wed, 05 Sep 2018 07:37:46 GMT-07:00

In-Center Hemodialysis: Time for a Paradigm Shift

Gul, Ambreen — Wed, 05 Sep 2018 07:37:45 GMT-07:00

Hereditary Kidney Disease: All Family Members Are Affected

Falke, Roberta M. — Tue, 11 Sep 2018 07:32:46 GMT-07:00

Perspective: Will We Ever Know the Optimal Hgb Level in ESRD?

Wish, Jay B. — Wed, 05 Sep 2018 07:37:46 GMT-07:00

MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension

Liu, Yong — Thu, 26 Jul 2018 06:21:56 GMT-07:00

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23

Robinson-Cohen, Cassianne — Fri, 14 Sep 2018 07:13:22 GMT-07:00

A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan

Chebib, Fouad T. — Tue, 18 Sep 2018 08:10:06 GMT-07:00

In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.

Kidney Transplantation Rates of Veterans Administration–Listed Patients Compared with Rates of Patients on Nonveteran Lists

Ramkumar, Mohan — Tue, 18 Sep 2018 08:10:06 GMT-07:00

Significantly Lower Rates of Kidney Transplantation among Candidates Listed with the Veterans Administration: A National and Local Comparison

Augustine, Joshua J. — Fri, 13 Jul 2018 12:30:04 GMT-07:00

Incident Atrial Fibrillation and the Risk of Stroke in Adults with Chronic Kidney Disease

Carrero, Juan Jesus — Fri, 20 Jul 2018 05:44:01 GMT-07:00

Management of the Incidental Kidney Mass in the Nephrology Clinic

Hu, Susie L. — Fri, 13 Apr 2018 07:18:23 GMT-07:00

A Patient with Hemodialysis Access Problems

Niyyar, Vandana Dua — Fri, 18 May 2018 07:33:48 GMT-07:00

This Month's Highlights

American Society of Nephrology — Fri, 31 Aug 2018 01:00:29 GMT-07:00

Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract

van der Ven, Amelie T. — Fri, 24 Aug 2018 05:40:27 GMT-07:00

Race, Ethnicity, and End-of-Life Care in Dialysis Patients in the United States

Foley, Robert N. — Thu, 09 Aug 2018 09:22:50 GMT-07:00

A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine

Xu, Xin — Fri, 27 Jul 2018 09:42:20 GMT-07:00

Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector

Ikeda, Yoichiro — Thu, 05 Jul 2018 05:18:05 GMT-07:00

Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient Mice

Yang, Yang — Tue, 24 Jul 2018 01:47:13 GMT-07:00

MUC1 Makes Me Miserable

Gale, Daniel P. — Fri, 17 Aug 2018 06:31:17 GMT-07:00

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

Kamburova, Elena G. — Thu, 26 Jul 2018 06:21:56 GMT-07:00

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

Novel Approaches for Assessment of Bone Turnover in CKD: Is New Always Better?

Gosmanova, Elvira O. — Mon, 30 Jul 2018 04:57:36 GMT-07:00

Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease

Živná, Martina — Mon, 02 Jul 2018 07:45:59 GMT-07:00

Authors' Reply

Salam, Syazrah — Mon, 30 Jul 2018 04:57:36 GMT-07:00

Erratum

American Society of Nephrology — Fri, 31 Aug 2018 01:00:29 GMT-07:00

Structural Basis of Highly Specific Interaction between Nephrin and MAGI1 in Slit Diaphragm Assembly and Signaling

Weng, Zhuangfeng — Fri, 13 Jul 2018 12:30:03 GMT-07:00

Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of Metformin

Lee, Mardiana — Thu, 05 Jul 2018 05:18:06 GMT-07:00

EGF Receptor–Dependent YAP Activation Is Important for Renal Recovery from AKI

Chen, Jianchun — Thu, 02 Aug 2018 06:57:07 GMT-07:00

Biallelic Expression of Mucin-1 in Autosomal Dominant Tubulointerstitial Kidney Disease: Implications for Nongenetic Disease Recognition

Knaup, Karl X. — Thu, 26 Jul 2018 06:21:55 GMT-07:00

ABCC6 Deficiency Promotes Development of Randall Plaque

Letavernier, Emmanuel — Tue, 10 Jul 2018 06:29:55 GMT-07:00

Association of Ambulatory Blood Pressure with All-Cause and Cardiovascular Mortality in Hemodialysis Patients: Effects of Heart Failure and Atrial Fibrillation

Mayer, Christopher C. — Wed, 25 Jul 2018 10:04:39 GMT-07:00

A New Pediatric AKI Definition: Implications of Trying to Build the Perfect Mousetrap

Goldstein, Stuart L. — Fri, 24 Aug 2018 05:40:28 GMT-07:00

Acute Declines in Renal Function during Intensive BP Lowering and Long-Term Risk of Death

Ku, Elaine — Fri, 13 Jul 2018 12:30:04 GMT-07:00

What Is the Glomerular Ultrafiltration Barrier?

Fissell, William H. — Fri, 20 Jul 2018 05:44:50 GMT-07:00

Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with Fabry Disease

Lenders, Malte — Thu, 09 Aug 2018 09:22:50 GMT-07:00

Mechanisms, Clinical Implications, and Treatment of Intradialytic Hypotension

Reeves, Patrick B. — Mon, 26 Feb 2018 07:10:35 GMT-08:00

Individuals with ESKD requiring maintenance hemodialysis face a unique hemodynamic challenge, typically on a thrice-weekly basis. In an effort to achieve some degree of euvolemia, ultrafiltration goals often involve removal of the equivalent of an entire plasma volume. Maintenance of adequate end-organ perfusion in this setting is dependent on the institution of a variety of complex compensatory mechanisms. Unfortunately, secondary to a myriad of patient- and dialysis-related factors, this compensation often falls short and results in intradialytic hypotension. Physicians and patients have developed a greater appreciation for the breadth of adverse outcomes associated with intradialytic hypotension, including higher cardiovascular and all-cause mortality. In this review, we summarize the evidence for adverse outcomes associated with intradialytic hypotension, explore the underlying pathophysiology, and use this as a basis to introduce potential strategies for its prevention and treatment.

Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

Shin, Jung-Im — Thu, 12 Jul 2018 05:23:58 GMT-07:00

Opportunities for Increasing the Rate of Preemptive Kidney Transplantation

Fishbane, Steven — Wed, 16 May 2018 08:01:29 GMT-07:00

Expand the Pool of Living Donors for Kidney Transplantation

Locke, Jayme E. — Mon, 16 Jul 2018 07:44:51 GMT-07:00

ABO-Incompatible Kidney Transplant Outcomes

de Weerd, Annelies E. — Mon, 16 Jul 2018 07:44:52 GMT-07:00

Communication Strategies to Address Conflict about Dialysis Decision Making for Critically Ill Patients

Schell, Jane O. — Mon, 16 Apr 2018 07:17:08 GMT-07:00

Thrombotic Microangiopathy in a Transplant Recipient

Mundra, Venkat Ram Rakesh — Tue, 24 Jul 2018 01:47:03 GMT-07:00

BP Measurement Techniques

Thomas, George — Mon, 26 Feb 2018 07:10:35 GMT-08:00

Patients with CKD typically have hypertension. Manual BP measurement in the office setting was used to define hypertension, establish eligibility, and assess BP targets in the epidemiologic studies and early randomized, controlled trials that inform current management of hypertension. Use of automated oscillometric devices has largely replaced manual BP measurement in the office and clinical trials. These newer devices may reduce the white coat effect and facilitate guideline-adherent measurement protocols. Obtaining BP measurements outside of the office with home and ambulatory BP monitoring is now more common. Out of office BPs are especially important in patients with CKD, because reduced GFR and proteinuria are associated with masked hypertension (normal office BP and elevated BP outside of the office), elevated nighttime BP, and abnormal diurnal variation in BP, all of which are associated with higher risk for target organ damage and adverse outcomes. Also, it is now feasible to routinely measure central BP and central hemodynamics. These measures are of greater importance to patients with CKD given the higher prevalence of increased sympathetic tone, arteriosclerosis, and inflammation as well as impaired sodium excretion and endothelial dysfunction, which lead to alterations in central BPs in this population. In this review, we describe various BP measurement techniques and how they apply to the care of patients with CKD.

Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD

Stremke, Elizabeth R. — Tue, 19 Jun 2018 08:09:54 GMT-07:00

Self-Reported Tobacco, Alcohol, and Illicit Drug Use and Progression of Chronic Kidney Disease

Bundy, Joshua D. — Thu, 07 Jun 2018 06:24:03 GMT-07:00

Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD

Luo, Shengyuan — Thu, 14 Jun 2018 06:51:37 GMT-07:00

Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome

Horinouchi, Tomoko — Fri, 29 Jun 2018 07:01:56 GMT-07:00

A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects

Mohammad, Jaber — Wed, 18 Jul 2018 06:18:28 GMT-07:00

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption. Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function. Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity. Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.

Erratum

American Society of Nephrology — Mon, 16 Jul 2018 07:45:00 GMT-07:00

AI: What Have You Done for Us Lately?

Torres, Richard — Tue, 19 Jun 2018 07:48:15 GMT-07:00

Erratum

American Society of Nephrology — Tue, 31 Jul 2018 01:00:38 GMT-07:00

Donald Seldin: A Transformative Leader in Medicine and Nephrology

Alpern, Robert — Mon, 09 Jul 2018 06:47:28 GMT-07:00

Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population

Jia, Xiaoyuan — Mon, 16 Jul 2018 07:44:59 GMT-07:00

Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay. Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10−23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10−25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10−9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10−12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10−11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor. Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.

A Single-Cell Transcriptome Atlas of the Mouse Glomerulus

Karaiskos, Nikos — Thu, 24 May 2018 06:17:29 GMT-07:00

Background Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown. Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli. Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations. Conclusions Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.

The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte Injury

Verheijden, Kim A.T. — Thu, 28 Jun 2018 06:16:55 GMT-07:00

Somatic Mutations in Renal Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease

Tan, Adrian Y. — Tue, 24 Jul 2018 01:47:12 GMT-07:00

Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI

Johnson, Ali C.M. — Fri, 06 Jul 2018 07:36:46 GMT-07:00

Prevention of Fatal C3 Glomerulopathy by Recombinant Complement Receptor of the Ig Superfamily

Wang, Xiaoxu — Tue, 12 Jun 2018 05:51:03 GMT-07:00

Background C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G. Methods We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (CRIg-Fc) in the treatment of C3G. CRIg-Fc binds C3b and inhibits C3 and C5 convertases of the AP. Mice with mutations in the factor H and properdin genes (FHm/mP−/−) develop early-onset C3G, with AP consumption, high proteinuria, and lethal crescentic GN. Results Treatment of FHm/mP−/− mice with CRIg-Fc, but not a control IgG, inhibited AP activation and diminished the consumption of plasma C3, factor B, and C5. CRIg-Fc–treated FHm/mP−/− mice also had significantly improved survival and reduced proteinuria, hematuria, BUN, glomerular C3 fragment, C9 and fibrin deposition, and GN pathology scores. Conclusions Therapeutics developed on the basis of the mechanism of action of soluble CRIg may be effective for the treatment of C3G and should be explored clinically.

The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study

Srivastava, Anand — Mon, 04 Jun 2018 05:45:35 GMT-07:00

Background Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data. Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT). Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m2. During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27). Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.

GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome

Hermle, Tobias — Fri, 29 Jun 2018 07:01:56 GMT-07:00

The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes

Hall, Gentzon — Thu, 12 Jul 2018 05:24:22 GMT-07:00

This Month's Highlights

American Society of Nephrology — Tue, 31 Jul 2018 01:00:38 GMT-07:00

Now or Later? Understanding Timing of Dialysis Initiation beyond IDEAL

Rifkin, Dena E. — Mon, 18 Jun 2018 08:23:05 GMT-07:00

Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD

Kurella Tamura, Manjula — Tue, 22 May 2018 06:31:27 GMT-07:00

Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function. Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65–74, 75–84, and ≥85 years), eGFR (<6, 6–<9, 9–<12, 12–<15, and 15–<29 ml/min per 1.73 m2), and provision of dialysis, and survival. Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65–74, 75–84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6–<9, <6, 9–<12, and 9–<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9–<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients. Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

Region-Based Convolutional Neural Nets for Localization of Glomeruli in Trichrome-Stained Whole Kidney Sections

Bukowy, John D. — Tue, 19 Jun 2018 07:48:15 GMT-07:00

Background Histologic examination of fixed renal tissue is widely used to assess morphology and the progression of disease. Commonly reported metrics include glomerular number and injury. However, characterization of renal histology is a time-consuming and user-dependent process. To accelerate and improve the process, we have developed a glomerular localization pipeline for trichrome-stained kidney sections using a machine learning image classification algorithm. Methods We prepared 4-μm slices of kidneys from rats of various genetic backgrounds that were subjected to different experimental protocols and mounted the slices on glass slides. All sections used in this analysis were trichrome stained and imaged in bright field at a minimum resolution of 0.92 μm per pixel. The training and test datasets for the algorithm comprised 74 and 13 whole renal sections, respectively, totaling over 28,000 glomeruli manually localized. Additionally, because this localizer will be ultimately used for automated assessment of glomerular injury, we assessed bias of the localizer for preferentially identifying healthy or damaged glomeruli. Results Localizer performance achieved an average precision and recall of 96.94% and 96.79%, respectively, on whole kidney sections without evidence of bias for or against glomerular injury or the need for manual preprocessing. Conclusions This study presents a novel and robust application of convolutional neural nets for the localization of glomeruli in healthy and damaged trichrome-stained whole-renal section mounts and lays the groundwork for automated glomerular injury scoring.

Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis

Assimon, Magdalene M. — Wed, 23 May 2018 06:48:20 GMT-07:00

Background Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established. Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan–Meier methods. Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in ≥30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations. Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy

Gonzalez-Quiroz, Marvin — Fri, 15 Jun 2018 07:25:54 GMT-07:00

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease. Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18–30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors. Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; −18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; −3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; −14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline. Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.

Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies

Daha, Mohamed R. — Tue, 19 Jun 2018 07:48:15 GMT-07:00

Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKD

van den Belt, Sophie M. — Thu, 21 Jun 2018 08:05:05 GMT-07:00

Background Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD. Methods In total, 280 eligible children with CKD stages 2–4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m2, 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m2 per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.5±1.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation. Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction <30%, 30%–60% and >60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction. Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD.

Single-Cell Sequencing the Glomerulus, Unraveling the Molecular Programs of Glomerular Filtration, One Cell at a Time

Kretzler, Matthias — Thu, 12 Jul 2018 05:24:21 GMT-07:00

C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe Hypertension

Timmermans, Sjoerd A.M.E.G. — Fri, 01 Jun 2018 05:33:56 GMT-07:00

Background Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay. Results Compared with normal human serum and samples from patients with hypertensive arterionephrosclerosis, 14 of 16 (87.5%) serum samples collected at presentation from 16 patients with hypertension-associated TMA induced abnormal C5b9 formation on microvascular endothelial cells. We detected rare variants in complement genes in eight of 17 (47%) patients. ESRD occurred in 14 of 17 (82%) patients, and recurrent TMA after transplant occurred in seven of 11 (64%) donor kidneys. Eculizumab improved the renal function in three patients and prevented TMA recurrence in an allograft recipient. Conclusions These observations point to complement defects as the key causative factor of ESRD and recurrent TMA after transplant in patients presenting with severe hypertension. Complement defects can be identified by measurements of complement activation on microvascular endothelial cells, which should substantially influence treatment and prognosis.

Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory Response

Wu, Haojia — Fri, 06 Jul 2018 07:36:45 GMT-07:00

Background Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.

Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future

Perazella, Mark A. — Fri, 29 Jun 2018 07:01:55 GMT-07:00

Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of “onco-nephrology” has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system–mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.

Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation

Harhay, Meera N. — Thu, 21 Jun 2018 08:02:42 GMT-07:00

The Affordable Care Act, Kidney Transplant Access, and Kidney Disease Care in the United States

Goyal, Nitender — Thu, 21 Jun 2018 08:02:42 GMT-07:00

The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China

Nie, Sheng — Mon, 18 Jun 2018 08:20:53 GMT-07:00

Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific Northwest

Sharma, Arjun — Fri, 15 Jun 2018 07:25:45 GMT-07:00

Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders

Higgins, Larissa — Wed, 30 May 2018 07:37:14 GMT-07:00

Management of Nonadherence in ESKD Patients

Cohen, Scott D. — Wed, 30 May 2018 07:37:13 GMT-07:00

Management of Osteoporosis in CKD

Khairallah, Pascale — Tue, 27 Feb 2018 08:03:56 GMT-08:00

CKD mineral and bone disease is a common complication of kidney disease, and it affects the majority of patients with moderate to severe CKD. Recently, prospective studies have shown that measurement of bone mineral density by dual energy x-ray absorptiometry predicts incident fracture, providing nephrologists the ability to risk classify patients for skeletal fragility and targeted antifracture strategies for the first time. Furthermore, an expanding body of literature and anecdotal evidence suggest that pharmacologic agents used to treat osteoporosis in the general population can be safely used in patients with CKD. This review highlights the effects of the Kidney Disease Improving Global Outcomes updates on the management of CKD-associated osteoporosis, discusses recent investigations on the effects of antiosteoporotic agents in patients with CKD, and provides an overview of novel antiosteoporosis agents and the potential challenges related to their use in CKD.

Parathyroidectomy in the Management of Secondary Hyperparathyroidism

Lau, Wei Ling — Fri, 09 Mar 2018 06:45:09 GMT-08:00

Secondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors. Hence, surgical parathyroidectomy should be considered, especially if concomitant disorders exist, such as persistent hypercalcemia or hyperphosphatemia, tissue or vascular calcification including calciphylaxis, and/or worsening osteodystrophy. Parathyroidectomy is associated with 15%–57% greater survival in patients on dialysis, and it also improves hypercalcemia, hyperphosphatemia, tissue calcification, bone mineral density, and health-related quality of life. The parathyroidectomy rate in the United States declined to approximately seven per 1000 dialysis patient-years between 2002 and 2011 despite an increase in average parathyroid hormone levels, reflecting calcimimetics introduction and uncertainty regarding optimal parathyroid hormone targets. Hospitalization rates are 39% higher in the first postoperative year. Hungry bone syndrome occurs in approximately 25% of patients on dialysis, and profound hypocalcemia requires high doses of oral and intravenous calcium along with calcitriol supplementation. Total parathyroidectomy with autotransplantation carries a higher risk of permanent hypocalcemia, whereas risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy. Given favorable long-term outcomes from observational parathyroidectomy cohorts, despite surgical risk and postoperative challenges, it is reasonable to consider parathyroidectomy in more patients with medically refractory secondary hyperparathyroidism.

Family Consultation to Reduce Early Hospital Readmissions among Patients with End Stage Kidney Disease

Jasinski, Matthew J. — Tue, 10 Apr 2018 08:00:29 GMT-07:00

Sleep Duration and Health-Related Quality of Life in Predialysis CKD

Sung, Su-Ah — Thu, 03 May 2018 06:45:14 GMT-07:00

IL-10 Receptor Signaling Empowers Regulatory T Cells to Control Th17 Responses and Protect from GN

Diefenhardt, Paul — Mon, 04 Jun 2018 05:45:36 GMT-07:00

Background Th17 cells are central pathogenic mediators of autoimmune disease, including many forms of GN. IL-10 receptor signaling (IL-10R) in regulatory T cells (Tregs) has been implicated in the downregulation of Th17 cells, but the underlying molecular mechanisms and functional relevance of this process remain unclear. Methods We generated mice with Treg-specific IL-10Ra deficiency and subjected these mice to nephrotoxic serum–induced nephritis as a model of crescentic GN. Immune responses and Treg phenotypes were extensively analyzed. Results Compared with controls, mice with IL-10Ra−/− Tregs showed a spontaneously overshooting Th17 immune response. This hyper-Th17 phenotype was further boosted during GN and associated with aggravated renal injury. Notably, abrogation of IL-10Ra signaling in Tregs increased dendritic cell activation and production of Th17-inducing cytokines. In contrast, Treg trafficking and expression of chemokine receptor CCR6 remained unaffected, indicating mechanisms of Th17 control, differing from those of previously identified CCR6+ Treg17 cells. Indeed, the capacity for direct in vitro suppression of Th17 responses by IL-10Ra−/− Tregs was significantly impaired. As underlying pathology, analyses conducted in vitro and in vivo using double-fluorescent reporter mice revealed strikingly decreased IL-10 production by IL-10Ra−/− Tregs. To assess, whether reduced IL-10 could explain the hyper Th17 phenotype, competitive cotransfer experiments were performed. Supporting our concept, IL-10Ra−/− T cells differentiated into Th17 cells at much higher frequencies than wild type T cells did during GN. Conclusions IL-10R engagement optimizes Treg-mediated suppression of Th17 immunity. We hypothesize a feed-forward loop, in which IL-10Ra signaling reinforces IL-10 secretion by Tregs which potently controls Th17 development via direct and indirect mechanisms. IL-10R thus may be a promising therapeutic target for the treatment of GN.

Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly Hemodialysis

Leong, Sheldon C. — Fri, 04 May 2018 05:56:20 GMT-07:00

Background Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. Methods We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Results Compared with anuric patients on thrice weekly dialysis with the same standard Kt/Vurea, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and p-cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Conclusions Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway

Bazúa-Valenti, Silvana — Wed, 30 May 2018 07:37:46 GMT-07:00

Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle’s loop controls Ca2+ excretion and NaCl reabsorption in response to extracellular Ca2+. However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22Na+ uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd3+. In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca2+ reabsorption, further promoting hypercalciuria.

This Month’s Highlights

American Society of Nephrology — Fri, 29 Jun 2018 01:05:02 GMT-07:00

Transformation in Immunosuppression: Are We Ready for it?

Aala, Amtul — Fri, 08 Jun 2018 06:44:39 GMT-07:00

Clinical and Pathology Findings Associate Consistently with Larger Glomerular Volume

Denic, Aleksandar — Tue, 22 May 2018 06:31:27 GMT-07:00

Background Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. Methods We studied kidney biopsy specimens from living kidney donors (n=2453) and patients who underwent radical nephrectomy for a renal tumor (n=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel–Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (P<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.

Erratum

American Society of Nephrology — Wed, 23 May 2018 06:48:20 GMT-07:00

Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion Injury

Yang, Bing — Wed, 20 Jun 2018 07:19:36 GMT-07:00

Background Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in the tubular and microvascular compartments during the various stages of IRI-induced AKI, and their relative importance to renal fibrogenesis. Methods We performed unilateral renal artery clamping for 30 minutes and contralateral nephrectomy in wild-type mice (C57BL/6) or caspase-3−/− mice. Results Compared with their wild-type counterparts, caspase-3−/− mice in the early stage of AKI had high urine cystatin C levels, tubular injury scores, and serum creatinine levels. Electron microscopy revealed evidence of tubular epithelial cell necrosis in caspase-3−/− mice, and immunohistochemistry showed upregulation of the necroptosis marker receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in renal cortical sections. Western blot analysis further demonstrated enhanced levels of phosphorylated RIPK3 in the kidneys of caspase-3−/− mice. In contrast, caspase-3−/− mice had less microvascular congestion and activation in the early and extension phases of AKI. In the long term (3 weeks after IRI), caspase-3−/− mice had reduced microvascular rarefaction and renal fibrosis, as well as decreased expression of α-smooth muscle actin and reduced collagen deposition within peritubular capillaries. Moreover, caspase-3−/− mice exhibited signs of reduced tubular ischemia, including lower tubular expression of hypoxia-inducible factor-1α and improved tubular injury scores. Conclusions These results establish the pivotal importance of caspase-3 in regulating microvascular endothelial cell apoptosis and renal fibrosis after IRI. These findings also demonstrate the predominant role of microvascular over tubular injury as a driver of progressive renal damage and fibrosis after IRI.

Epithelial and Endothelial Pannexin1 Channels Mediate AKI

Jankowski, Jakub — Mon, 04 Jun 2018 05:45:34 GMT-07:00

Background Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation. Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI. Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI. Furthermore, global deletion of Panx1 preserved kidney function and morphology and diminished the expression of proinflammatory molecules after IRI. Analysis of bone marrow chimeric mice revealed that Panx1 expressed on parenchymal cells is necessary for ischemic injury, and both proximal tubule and vascular endothelial Panx1 tissue-specific knockout mice were protected from IRI. In vitro, Panx1-deficient proximal tubule cells released less and retained more ATP under hypoxic stress. Conclusions Panx1 is involved in regulating ATP release from hypoxic cells, and reducing this ATP release may protect kidneys from AKI.

Cellular Origin and Functional Relevance of Collagen I Production in the Kidney

Buchtler, Simone — Fri, 18 May 2018 07:34:02 GMT-07:00

Background Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow–derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear. Methods We generated conditional cell type–specific collagen I knockout mice and used (reversible) unilateral ureteral obstruction and adenine-induced nephropathy to study renal fibrosis and function. Results In these mouse models, hematopoietic, bone marrow–derived cells contributed to 38%–50% of the overall deposition of collagen I in the kidney. The influence of fibrosis on renal function was dependent on the type of damage. In unilateral ureteral obstruction, collagen production by resident fibroblasts was essential to preserve renal function, whereas in the chronic model of adenine-induced nephropathy, collagen production was detrimental to renal function. Conclusions Our data show that hematopoietic cells are a major source of collagen and that antifibrotic therapies need to be carefully considered depending on the type of disease and the underlying cause of fibrosis.

Greater Burden of ESRD among Immigrants: Kwa nini?

Crews, Deidra C. — Mon, 04 Jun 2018 05:45:35 GMT-07:00

GATM Mutations Cause a Dominant Fibrillar Conformational Disease in Mitochondria—When Eternity Kills

Courtoy, Pierre J. — Tue, 22 May 2018 06:31:28 GMT-07:00

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Marthi, Amarnath — Tue, 15 May 2018 10:06:29 GMT-07:00

Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43–74 RU/ml and 38–47 pg/ml in 17 general population cohorts; 102–392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79–4212 RU/ml and 2526–5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure–response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.

ESRD among Immigrants to Ontario, Canada: A Population-Based Study

Perl, Jeffrey — Wed, 02 May 2018 05:57:02 GMT-07:00

Background The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear. Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group. Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants. Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations.

Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane

Morelle, Johann — Tue, 29 May 2018 07:21:49 GMT-07:00

Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.

Leveraging Ancestral Heterogeneity to Map Shared Genetic Risk Loci in Pediatric Steroid-Sensitive Nephrotic Syndrome

Hjorten, Rebecca — Thu, 14 Jun 2018 06:51:54 GMT-07:00

Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia

Ueda, Yoshiyasu — Fri, 01 Jun 2018 05:33:55 GMT-07:00

Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality. Results P deficiency completely rescued FHR/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice. Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression

Tin, Adrienne — Fri, 18 May 2018 07:34:03 GMT-07:00

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles—genetic variants associated with CKD risk commonly present in persons of African descent—may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) (n=588; Bonferroni significance threshold P<6.5×10−5) and replicated findings in 678 black participants with CKD in BioMe, an electronic medical record–linked biobank. We tested the metabolite association with CKD progression in AASK, BioMe, and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK (P=4.7×10−5) and replicated in BioMe (P=5.7×10−3) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and BioMe participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; BioMe, 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression.

Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients

Ishida, Julie H. — Tue, 05 Jun 2018 06:51:04 GMT-07:00

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking. Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0–100, >100–200, >200–300, and >300 mg) and pregabalin (>0–100 and >100 mg). Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%–41%) and fall (26%–30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively. Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.

A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease

Ilatovskaya, Daria V. — Wed, 23 May 2018 06:48:21 GMT-07:00

Background Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). We hypothesized that NOX4-derived H2O2 contributes to podocyte damage in DKD via elevation of podocyte calcium. Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SSNox4−/−) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6. We performed whole animal studies and used biosensor measurements, electron microscopy, electrophysiology, and live calcium imaging experiments to evaluate the contribution of this pathway to the physiology of the podocytes in freshly isolated glomeruli. Results Upon induction of type 1 diabetes with streptozotocin, SSNox4−/− rats exhibited significantly lower basal intracellular Ca2+ levels in podocytes and less DKD-associated damage than SS rats did. Furthermore, the angiotensin II–elicited calcium flux was blunted in glomeruli isolated from diabetic SSNox4−/− rats compared with that in glomeruli from diabetic SS rats. H2O2 stimulated TRPC-dependent calcium influx in podocytes from wild-type mice, but this influx was blunted in podocytes from Trpc6-knockout mice and, in a similar manner, in podocytes from Trpc5/6 double-knockout mice. Finally, electron microscopy revealed that podocytes of glomeruli isolated from Trpc6-knockout or Trpc5/6 double-knockout mice were protected from damage induced by H2O2 to the same extent. Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.

Right Heart Failure—Unrecognized Cause of Cardiorenal Syndrome

Bansal, Shweta — Tue, 15 May 2018 10:06:28 GMT-07:00

Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome

Debiec, Hanna — Thu, 14 Jun 2018 06:51:54 GMT-07:00

Background Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis-expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3′ untranslated region of HLA-DQB1 (P=9.3×10−23). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P=3.7×10−11) and in the 3′ untranslated region of BTNL2 (rs9348883, P=9.4×10−7) within introns of HCG23 and LOC101929163. These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure

Reichold, Markus — Fri, 13 Apr 2018 07:22:18 GMT-07:00

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations. Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death. Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.

The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases

Sethi, Sanjeev — Fri, 27 Apr 2018 06:04:49 GMT-07:00

Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a “benign” hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.

Sirtuins in Renal Health and Disease

Morigi, Marina — Mon, 30 Apr 2018 07:14:45 GMT-07:00

Sirtuins belong to an evolutionarily conserved family of NAD+-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1–7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.

Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

Pascual, Julio — Fri, 11 May 2018 06:12:23 GMT-07:00

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin. Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events. Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

This Month’s Highlights

American Society of Nephrology — Mon, 30 Apr 2018 01:05:26 GMT-07:00

Insights into CKD from Metabolite GWAS

Liu, Lili — Tue, 10 Apr 2018 08:02:06 GMT-07:00

Repairing the GBM Step by Step

Tufro, Alda — Thu, 12 Apr 2018 05:06:13 GMT-07:00

The Authors Reply

Kumar, Vivek — Fri, 09 Mar 2018 06:45:31 GMT-08:00

Studying the Effect of Vitamin D Supplementation on Vascular Function in CKD: A Work in Progress

Nwaohiri, Nnamdi Kelechi — Fri, 09 Mar 2018 06:45:31 GMT-08:00

Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms

Li, Yong — Thu, 15 Mar 2018 07:06:24 GMT-07:00

Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios. These included associations already known from population-based studies. Additional findings included an association for the uremic toxin putrescine and variants upstream of an enzyme catalyzing the oxidative deamination of polyamines (AOC1, P-min=2.4×10−12), a relatively high carrier frequency (2%) for rare deleterious missense variants in ACADM that are collectively associated with serum ratios of medium-chain acylcarnitines (P-burden=6.6×10−16), and associations of a common variant in SLC7A9 with several ratios of lysine to neutral amino acids in urine, including the lysine/glutamine ratio (P=2.2×10−23). The associations of this SLC7A9 variant with ratios of lysine to specific neutral amino acids were much stronger than the association with lysine concentration alone. This finding is consistent with SLC7A9 functioning as an exchanger of urinary cationic amino acids against specific intracellular neutral amino acids at the apical membrane of proximal tubular cells. Conclusions Metabolomic indices of specific kidney functions in genetic studies may provide insight into human renal physiology.

Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models

Embry, Addie E. — Fri, 23 Mar 2018 05:56:29 GMT-07:00

Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.

Antibodies Can Extenuate Polyomavirus Infections

Nickeleit, Volker — Wed, 21 Feb 2018 06:32:22 GMT-08:00

JASN this Month: Something Old, Something New

Briggs, Josephine — Wed, 04 Apr 2018 06:47:32 GMT-07:00

Using Large Datasets to Understand CKD

Drysdale, Thomas A. — Wed, 11 Apr 2018 04:32:52 GMT-07:00

The Authors Reply

Solis, Morgane — Wed, 21 Feb 2018 06:32:21 GMT-08:00

Gpr97 Exacerbates AKI by Mediating Sema3A Signaling

Fang, Wei — Mon, 12 Mar 2018 05:59:02 GMT-07:00

Background G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI. Methods AKI was induced by ischemia–reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function. Results Gpr97 was upregulated in the kidneys from mice with AKI and patients with biopsy-proven acute tubular necrosis compared with healthy controls. In AKI models, Gpr97-deficient mice had significantly less renal injury and inflammation than wild-type mice. Gpr97 deficiency also attenuated the AKI-induced expression of semaphorin 3A (Sema3A), a potential early diagnostic biomarker of renal injury. In NRK-52E cells subjected to oxygen–glucose deprivation, siRNA-mediated knockdown of Gpr97 further increased the expression of survivin and phosphorylated STAT3 and reduced toll-like receptor 4 expression. Cotreatment with recombinant murine Sema3A protein counteracted these effects. Finally, additional in vivo and in vitro studies, including electrophoretic mobility shift assays and luciferase reporter assays, showed that Gpr97 deficiency attenuates ischemia–reperfusion-induced expression of the RNA-binding protein human antigen R, which post-transcriptionally regulates Sema3A expression. Conclusions Gpr97 is an important mediator of AKI, and pharmacologic targeting of Gpr97-mediated Sema3A signaling at multiple levels may provide a novel approach for the treatment of AKI.

The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy

Seifert, Larissa — Mon, 19 Mar 2018 06:16:42 GMT-07:00

Background Thrombospondin type 1 domain–containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown. Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice. Results We characterized the extracellular topology of THSD7A as a tandem string of 21 thrombospondin type 1 domains. Overall, 28 serum samples (90%) recognized multiple epitope domains along the molecule. Detailed epitope mapping revealed that the complex consisting of the first and second N-terminal domains (amino acids 48–192) was recognized by 27 of 31 patient serum samples (87%). Serum recognizing one or two epitope domains showed lower anti-THSD7A antibody levels than serum recognizing three or more epitope domains. During follow-up, a loss of epitope recognition was observed in seven of 16 patients, and it was accompanied by decreasing antibody levels and remission of proteinuria. In four of 16 patients, epitope recognition patterns changed during follow-up. Notably, immunization experiments in rabbits and mice revealed that induced antibodies, like patient autoantibodies, preferentially bound to the most N-terminal domains of THSD7A. Conclusions Our data show that the immune response in THSD7A-associated MN is polyreactive and that autoantibodies predominantly target the most N-terminal part of THSD7A.

Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK Pathway

Fukusumi, Yoshiyasu — Fri, 30 Mar 2018 07:04:25 GMT-07:00

Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy. Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1–promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy. Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.

Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKD

Prokop, Jeremy W. — Fri, 23 Feb 2018 11:41:35 GMT-08:00

Background Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data from patients. For example, SHROOM3 is an associated risk gene for CKD, yet causative mechanism(s) of SHROOM3 allele(s) are unknown. Methods We used our analytic pipeline that integrates genetic, computational, biochemical, CRISPR/Cas9 editing, molecular, and physiologic data to characterize coding and noncoding variants to study the human SHROOM3 risk locus for CKD. Results We identified a novel SHROOM3 transcriptional start site, which results in a shorter isoform lacking the PDZ domain and is regulated by a common noncoding sequence variant associated with CKD (rs17319721, allele frequency: 0.35). This variant disrupted allele binding to the transcription factor TCF7L2 in podocyte cell nuclear extracts and altered transcription levels of SHROOM3 in cultured cells, potentially through the loss of repressive looping between rs17319721 and the novel start site. Although common variant mechanisms are of high utility, sequencing is beginning to identify rare variants involved in disease; therefore, we used our biophysical tools to analyze an average of 112,849 individual human genome sequences for rare SHROOM3 missense variants, revealing 35 high-effect variants. The high-effect alleles include a coding variant (P1244L) previously associated with CKD (P=0.01, odds ratio=7.95; 95% CI, 1.53 to 41.46) that we find to be present in East Asian individuals at an allele frequency of 0.0027. We determined that P1244L attenuates the interaction of SHROOM3 with 14–3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD. Conclusions These data demonstrate multiple new SHROOM3-dependent genetic/molecular mechanisms that likely affect CKD.

Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration

Schiessl, Ina Maria — Fri, 23 Feb 2018 11:41:35 GMT-08:00

Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule

Sun, Qifei — Fri, 30 Mar 2018 07:04:24 GMT-07:00

Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro, autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK, with or without Drosophila Mo25, did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux. Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium.

Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPβ in Vasopressin-Sensitive Collecting Duct Cells

Jung, Hyun Jun — Fri, 23 Mar 2018 05:56:29 GMT-07:00

Background Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene (Aqp2). Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell–specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II. Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein-β (C/EBPβ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBPβ, a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2. However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2. Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect. Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBPβ (but not CREB) binding.

Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome

Lin, Meei-Hua — Thu, 22 Feb 2018 07:39:40 GMT-08:00

Background Laminin α5β2γ1 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity. Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2−/− pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture. Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM. Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.

Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Greenberg, Jason H. — Thu, 22 Feb 2018 07:39:41 GMT-08:00

Background As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. Methods On the first day of serum creatinine–defined AKI, we measured urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days). Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.

Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

Salam, Syazrah — Mon, 19 Mar 2018 06:16:42 GMT-07:00

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry. Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD. Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested. Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

The Quest for Better Biomarkers of Bone Turnover in CKD

Nickolas, Thomas L. — Thu, 12 Apr 2018 05:06:13 GMT-07:00

WNKs on the Fly

Welling, Paul A. — Thu, 12 Apr 2018 05:06:13 GMT-07:00

Mechanism of Hyperkalemia-Induced Metabolic Acidosis

Harris, Autumn N. — Mon, 26 Feb 2018 07:11:49 GMT-08:00

Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs. Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)–specific overexpression of constitutively active Ste20/SPS1-related proline-alanine–rich kinase (DCT-CA-SPAK). Results DCT-CA-SPAK mice developed hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion; however, titratable acid excretion and urine pH were unchanged compared with those in wild-type mice. Abnormal ammonia excretion in DCT-CA-SPAK mice associated with decreased proximal tubule expression of the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase and overexpression of the ammonia-recycling enzyme glutamine synthetase. These mice also had decreased expression of the ammonia transporter family member Rhcg and decreased apical polarization of H+-ATPase in the inner stripe of the outer medullary collecting duct. Correcting the hyperkalemia by treatment with hydrochlorothiazide corrected the metabolic acidosis, increased ammonia excretion, and normalized ammoniagenic enzyme and Rhcg expression in DCT-CA-SPAK mice. In wild-type mice, induction of hyperkalemia by administration of the epithelial sodium channel blocker benzamil caused hyperkalemia and suppressed ammonia excretion. Conclusions Hyperkalemia decreases proximal tubule ammonia generation and collecting duct ammonia transport, leading to impaired ammonia excretion that causes metabolic acidosis.

Protein S Protects against Podocyte Injury in Diabetic Nephropathy

Zhong, Fang — Tue, 06 Mar 2018 06:04:32 GMT-08:00

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose–induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose– and TNF-α–induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression.

Lipoxins Regulate the Early Growth Response–1 Network and Reverse Diabetic Kidney Disease

Brennan, Eoin P. — Wed, 28 Feb 2018 07:19:10 GMT-08:00

Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4) as therapeutics in a murine model of diabetic kidney disease, ApoE−/− mice treated with streptozotocin. Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF-α, IL-1β, NF-κB). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA4 and Benzo-LXA4, respectively, and pathway analysis identified established (TGF-β1, PDGF, TNF-α, NF-κB) and novel (early growth response–1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF-α–driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF-β1 and TNF-α. Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation.

The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD

Loutradis, Charalampos — Wed, 28 Mar 2018 06:47:48 GMT-07:00

Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; i.e., they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non–myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.

HDL in CKD—The Devil Is in the Detail

Kronenberg, Florian — Thu, 22 Feb 2018 07:39:41 GMT-08:00

The picture of HDL cholesterol (HDL-C) as the “good” cholesterol has eroded. This is even more surprising because there exists strong evidence that HDL-C is associated with cardiovascular disease (CVD) in the general population as well as in patients with impairment of kidney function and/or progression of CKD. However, drugs that dramatically increase HDL-C have mostly failed to decrease CVD events. Furthermore, genetic studies took the same line, as genetic variants that have a pronounced influence on HDL-C concentrations did not show an association with cardiovascular risk. For many, this was not surprising, given that an HDL particle is highly complex and carries >80 proteins and several hundred lipid species. Simply measuring cholesterol might not reflect the variety of biologic effects of heterogeneous HDL particles. Therefore, functional studies and the involvement of HDL components in the reverse cholesterol transport, including the cholesterol efflux capacity, have become a further focus of study during recent years. As also observed for other aspects, CKD populations behave differently compared with non-CKD populations. Although clear disturbances have been observed for the “functionality” of HDL particles in patients with CKD, this did not necessarily translate into clear-cut associations with outcomes.

The APOL1 Long-Term Kidney Transplantation Outcomes Network—APOLLO

Freedman, Barry I. — Fri, 27 Apr 2018 06:04:37 GMT-07:00

Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell Transplantation

Hingorani, Sangeeta — Wed, 18 Apr 2018 07:10:54 GMT-07:00

Approach to the Young Patient with New-Onset Hypertension

Cohen, Debbie L. — Fri, 23 Feb 2018 11:41:48 GMT-08:00

A Patient with Hemolytic Uremic Syndrome and Kidney Failure

Thurman, Joshua M. — Mon, 19 Feb 2018 06:20:33 GMT-08:00

A Case of Monoclonal Gammopathy of Renal Significance

Hogan, Jonathan J. — Fri, 18 May 2018 07:33:48 GMT-07:00

Identification of Patients Expected to Benefit from Electronic Alerts for Acute Kidney Injury

Biswas, Aditya — Thu, 29 Mar 2018 06:09:56 GMT-07:00

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events

Go, Alan S. — Thu, 17 May 2018 06:08:05 GMT-07:00

Biomarkers Associated with Progression of Diabetic Kidney Disease: Do They Hold the Same Meaning for Blacks and Women?

Hickson, LaTonya J. — Fri, 20 Apr 2018 07:37:29 GMT-07:00

Diet Patterns—A Neglected Aspect of Hemodialysis Care

Logan, Alexander G. — Fri, 18 May 2018 07:34:02 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Thu, 31 May 2018 01:05:08 GMT-07:00

The Authors Reply

Lv, Lin-Li — Wed, 25 Apr 2018 06:25:11 GMT-07:00

Nanoparticle Tracking Analysis of Urine to Detect Exosomes Can Be Confounded by Albuminuria

Gleadle, Jonathan — Wed, 25 Apr 2018 06:25:11 GMT-07:00

NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRD

Snoek, Rozemarijn — Fri, 13 Apr 2018 07:22:17 GMT-07:00

Background Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous NPHP1 full gene deletions in adult-onset ESRD. Methods Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at ≥18 years old. Results We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18–61) years old for patients with NPH, with 54% of patients age ≥30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%). Conclusions Considering that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.

Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis

Lemos, Dario R. — Tue, 08 May 2018 08:08:24 GMT-07:00

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo, in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro, stimulation of purified human kidney SCs and human kidney organoids with IL-1β recapitulated the molecular events observed in vivo, inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1β and metabolic switch in fibrosis initiation and progression and highlight IL-1β and MYC as potential therapeutic targets in tubulointerstitial diseases.

Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κB

Voelkl, Jakob — Fri, 13 Apr 2018 07:22:16 GMT-07:00

Background The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear. Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD. Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α–induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs. Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.

The Authors Reply

Coca, Steven G. — Fri, 20 Apr 2018 07:37:28 GMT-07:00

Oral Antibiotic Exposure and Kidney Stone Disease

Tasian, Gregory E. — Thu, 10 May 2018 08:01:16 GMT-07:00

Background Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case–control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Results Exposure to any of five different antibiotic classes 3–12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3–6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3–5 years from exposure. Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.

Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways

Zacchia, Miriam — Fri, 20 Apr 2018 07:37:28 GMT-07:00

Background Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na+-dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity. Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ETB and measured [14C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification. Wild-type (Pyk2+/+) and Pyk2-null (Pyk2−/−) mice were exposed to NH4Cl loading and euthanized after various end points, at which time we harvested the kidneys for immunoblotting and brush border membrane NaDC-1 activity studies. Results Inhibition of Pyk2 or c-Src prevented acid stimulation but not ET-1 stimulation of NaDC-1 in vitro. Consistent with these results, NH4Cl loading stimulated NaDC-1 activity in kidneys of wild-type but not Pyk2−/− mice. In cultured cells and in mice, ERK1/2 was rapidly phosphorylated by acid loading, even after Pyk2 knockdown, and it was required for acid but not ET-1/ETB stimulation of NaDC-1 in vitro. Media acidification also induced the phosphorylation of Raf1 and p90RSK, components of the ERK1/2 pathway, and inhibition of these proteins blocked acid stimulation of NaDC-1 activity. Conclusions Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling pathways, but these pathways are not downstream of ET-1/ETB in this process.

The Role of Palladin in Podocytes

Artelt, Nadine — Wed, 02 May 2018 05:57:03 GMT-07:00

Background Podocyte loss and effacement of interdigitating podocyte foot processes are the major cause of a leaky filtration barrier and ESRD. Because the complex three-dimensional morphology of podocytes depends on the actin cytoskeleton, we studied the role in podocytes of the actin bundling protein palladin, which is highly expressed therein. Methods We knocked down palladin in cultured podocytes by siRNA transfection or in zebrafish embryos by morpholino injection and studied the effects by immunofluorescence and live imaging. We also investigated kidneys of mice with podocyte-specific knockout of palladin (PodoPalld−/− mice) by immunofluorescence and ultrastructural analysis and kidney biopsy specimens from patients by immunostaining for palladin. Results Compared with control-treated podocytes, palladin-knockdown podocytes had reduced actin filament staining, smaller focal adhesions, and downregulation of the podocyte-specific proteins synaptopodin and α-actinin-4. Furthermore, palladin-knockdown podocytes were more susceptible to disruption of the actin cytoskeleton with cytochalasin D, latrunculin A, or jasplakinolide and showed altered migration dynamics. In zebrafish embryos, palladin knockdown compromised the morphology and dynamics of epithelial cells at an early developmental stage. Compared with PodoPalld+/+ controls, PodoPalld−/− mice developed glomeruli with a disturbed morphology, an enlarged subpodocyte space, mild effacement, and significantly reduced expression of nephrin and vinculin. Furthermore, nephrotoxic serum injection led to significantly higher levels of proteinuria in PodoPalld−/− mice than in controls. Kidney biopsy specimens from patients with diabetic nephropathy and FSGS showed downregulation of palladin in podocytes as well. Conclusions Palladin has an important role in podocyte function in vitro and in vivo.

The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort Study

Saglimbene, Valeria M. — Wed, 25 Apr 2018 06:25:11 GMT-07:00

Background Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain. Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category). Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients. Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.

Cooperation of Antiporter LAT2/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino Acids

Vilches, Clara — Mon, 02 Apr 2018 06:38:35 GMT-07:00

Background Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y+LAT1/CD98hc (SLC7A7/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2/CD98hc (SLC7A8/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2/CD98hc has been suggested by in vitro studies but has not been evaluated in vivo. Methods To study the functional relationship of TAT1 and LAT2/CD98hc in vivo, we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2/CD98hc (dKO LAT2-TAT1 mice). Results Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y+LAT1/CD98hc. Conclusions The LAT2/CD98hc and TAT1 transporters functionally cooperate in vivo, and y+LAT1/CD98hc may compensate for the loss of LAT2/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans.

A Novel Method for Rapid Bedside Measurement of GFR

Rizk, Dana V. — Thu, 10 May 2018 08:01:14 GMT-07:00

Background Direct quantitative measurement of GFR (mGFR) remains a specialized task primarily performed in research settings. Multiple formulas for estimating GFR have been developed that use the readily available endogenous biomarkers creatinine and/or cystatin C. However, eGFR formulas have limitations, and an accurate mGFR is necessary in some clinical situations and for certain patient populations. We conducted a prospective, open-label study to evaluate a novel rapid technique for determining plasma volume and mGFR. Methods We developed a new exogenous biomarker, visible fluorescent injectate (VFI), consisting of a large 150-kD rhodamine derivative and small 5-kD fluorescein carboxymethylated dextrans. After a single intravenous injection of VFI, plasma volume and mGFR can be determined on the basis of the plasma pharmacokinetics of the rhodamine derivative and fluorescein carboxymethylated dextrans, respectively. In this study involving 32 adults with normal kidney function (n=16), CKD stage 3 (n=8), or CKD stage 4 (n=8), we compared VFI-based mGFR values with values obtained by measuring iohexol plasma disappearance. VFI-based mGFR required three 0.5-ml blood draws over 3 hours; iohexol-based mGFR required five samples taken over 6 hours. Eight healthy participants received repeat VFI injections at 24 hours. Results VFI-based mGFR values showed close linear correlation with the iohexol-based mGFR values in all participants. Injections were well tolerated, including when given on consecutive days. No serious adverse events were reported. VFI-based mGFR was highly reproducible. Conclusions The VFI-based approach allows for the rapid determination of mGFR at the bedside while maintaining patient safety and measurement accuracy and reproducibility.

Hydroxyproline Metabolism and Oxalate Synthesis in Primary Hyperoxaluria

Fargue, Sonia — Tue, 27 Mar 2018 05:53:05 GMT-07:00

Background Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate. However, the relative contribution of Hyp metabolism to endogenous oxalate and glycolate synthesis is not known. Methods To define this contribution, we performed primed, continuous, intravenous infusions of the stable isotope [15N,13C5]-Hyp in nine healthy subjects and 19 individuals with PH and quantified the levels of urinary 13C2-oxalate and 13C2-glycolate formed using ion chromatography coupled to mass detection. Results The total urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and 10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls, respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was 15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3, respectively. The contribution of Hyp to urinary glycolate was 57% in controls, 30% in subjects with PH1, and <13% in subjects with PH2 or PH3. Conclusions Hyp metabolism differs among PH types and is a major source of oxalate synthesis in individuals with PH2 and PH3. In patients with PH1, who have the highest urinary excretion of oxalate, the major sources of oxalate remain to be identified.

The Underestimated Burden of Monogenic Diseases in Adult-Onset ESRD

Cornec-Le Gall, Emilie — Wed, 16 May 2018 08:01:45 GMT-07:00

Depletion of Gprc5a Promotes Development of Diabetic Nephropathy

Ma, Xiaojie — Tue, 10 Apr 2018 08:02:07 GMT-07:00

Background Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression. Methods To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein–coupled receptors (GPCRs) using human glomeruli. Results We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-β signaling and activation of the EGF receptor in cultured podocytes. Conclusions Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.

Does the Receipt of Antibiotics for Common Infectious Diseases Predispose to Kidney Stones? A Cautionary Note for All Health Care Practitioners

Nazzal, Lama — Thu, 10 May 2018 08:01:15 GMT-07:00

Metabolomics Research in Chronic Kidney Disease

Grams, Morgan E. — Thu, 03 May 2018 06:45:34 GMT-07:00

Protein Mass Spectrometry Made Simple

Klein, Jon B. — Thu, 03 May 2018 06:45:34 GMT-07:00

Vascularizing the Kidney in the Embryo and Organoid: Questioning Assumptions about Renal Vasculogenesis

Munro, David A.D. — Thu, 10 May 2018 08:01:14 GMT-07:00

The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter Expression

Nanami, Masayoshi — Thu, 17 May 2018 06:08:17 GMT-07:00

Background Nedd4–2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4–2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4–2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4–2 knockout mice using Cre-lox technology and produced global pendrin/Nedd4–2 null mice by breeding global Nedd4–2 null (Nedd4–2−/−) mice with global pendrin null (Slc26a4−/−) mice. Mice ate a diet with 1%–4% NaCl; BP was measured by tail cuff and radiotelemetry. We measured transepithelial transport of Cl− and total CO2 and transepithelial voltage in cortical collecting ducts perfused in vitro. Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry. Results IC Nedd4–2 gene ablation markedly increased electroneutral Cl−/HCO3− exchange in the cortical collecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little. IC Nedd4–2 gene ablation did not increase the abundance of type B IC transporters, such as AE4 (Slc4a9), H+-ATPase, barttin, or the Na+-dependent Cl−/HCO3− exchanger (Slc4a8). However, IC Nedd4–2 gene ablation increased CIC-5 total protein abundance, apical plasma membrane pendrin abundance, and the ratio of pendrin expression on the apical membrane to the cytoplasm. IC Nedd4–2 gene ablation increased BP by approximately 10 mm Hg. Moreover, pendrin gene ablation eliminated the increase in BP observed in global Nedd4–2 knockout mice. Conclusions IC Nedd4–2 regulates Cl−/HCO3− exchange in ICs., Nedd4–2 gene ablation increases BP in part through its action in these cells.

An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy

Yang, Yi — Tue, 27 Mar 2018 05:53:06 GMT-07:00

Background C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1–5 linked to repeats 18–20 (FH1–5^18–20), that was effective in experimental C3G. However, the serum t1/2 of FH1–5^18–20 was significantly shorter than that of serum-purified FH. Methods We introduced the oligomerization domain of human FH-related protein 1 (denoted by R1–2) at the carboxy or amino terminus of human FH1–5^18–20 to generate two homodimeric mini-FH constructs (FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2, respectively) in Chinese hamster ovary cells and tested these constructs using binding, fluid-phase, and erythrocyte lysis assays, followed by experiments in FH-deficient Cfh−/− mice. Results FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2 homodimerized in solution and displayed avid binding profiles on clustered C3b surfaces, particularly FHR1–2^1–5^18–20. Each construct was >10-fold more effective than FH at inhibiting cell surface complement activity in vitro and restricted glomerular basement membrane C3 deposition in vivo significantly better than FH or FH1–5^18–20. FH1–5^18–20^R1–2 had a C3 breakdown fragment binding profile similar to that of FH, a >5-fold increase in serum t1/2 compared with that of FH1–5^18–20, and significantly better retention in the kidney than FH or FH1–5^18–20. Conclusions FH1–5^18–20^R1–2 may have utility as a treatment option for C3G or other complement-mediated diseases.

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

Szeto, Cheuk-Chun — Tue, 17 Apr 2018 05:50:06 GMT-07:00

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.

Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival

See, Sarah B. — Fri, 30 Mar 2018 07:04:24 GMT-07:00

Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens. Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde. Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss. Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.

Four-Dimensional Imaging of T Cells in Kidney Transplant Rejection

Hughes, Andrew D. — Fri, 13 Apr 2018 07:22:17 GMT-07:00

Kidney transplantation is the treatment of choice for ESRD but is complicated by the response of the recipient’s immune system to nonself histocompatibility antigens on the graft, resulting in rejection. Multiphoton intravital microscopy, referred to as four-dimensional imaging because it records dynamic events in three-dimensional tissue volumes, has emerged as a powerful tool to study immunologic processes in living animals. Here, we will review advances in understanding the complex mechanisms of T cell–mediated rejection made possible by four-dimensional imaging of mouse renal allografts. We will summarize recent data showing that activated (effector) T cell migration to the graft is driven by cognate antigen presented by dendritic cells that surround and penetrate peritubular capillaries, and that T cell–dendritic cell interactions persist in the graft over time, maintaining the immune response in the tissue.

Incidence, Risk Factors, and Sequelae of Post-kidney Transplant Delirium

Haugen, Christine E. — Mon, 23 Apr 2018 05:36:58 GMT-07:00

Background Frail kidney transplant (KT) recipients may be particularly vulnerable to surgical stressors, resulting in delirium and subsequent adverse outcomes. We sought to identify the incidence, risk factors, and sequelae of post-KT delirium. Methods We studied 125,304 adult KT recipients (1999–2014) to estimate delirium incidence in national registry claims. Additionally, we used a validated chart abstraction algorithm to identify post-KT delirium in 893 adult recipients (2009–2017) from a cohort study of frailty. Delirium sequelae were identified using adjusted logistic regression (length of stay ≥2 weeks and institutional discharge [skilled nursing or rehabilitation facility]) and adjusted Cox regression (death-censored graft loss and mortality). Results Only 0.8% of KT recipients had a delirium claim. In the cohort study, delirium incidence increased with age (18–49 years old: 2.0%; 50–64 years old: 4.6%; 65–75 years old: 9.2%; and ≥75 years old: 13.8%) and frailty (9.0% versus 3.9%); 20.0% of frail recipients aged ≥75 years old experienced delirium. Frailty was independently associated with delirium (odds ratio [OR], 2.05; 95% confidence interval [95% CI], 1.02 to 4.13; P=0.04), but premorbid global cognitive function was not. Recipients with delirium had increased risks of ≥2-week length of stay (OR, 5.42; 95% CI, 2.76 to 10.66; P<0.001), institutional discharge (OR, 22.41; 95% CI, 7.85 to 63.98; P<0.001), graft loss (hazard ratio [HR], 2.73; 95% CI, 1.14 to 6.53; P=0.03), and mortality (HR, 3.12; 95% CI, 1.76 to 5.54; P<0.001). Conclusions Post-KT delirium is a strong risk factor for subsequent adverse outcomes, yet it is a clinical entity that is often missed.

Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction

Sheybani-Deloui, Sepideh — Mon, 06 Nov 2017 06:04:24 GMT-08:00

Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm–derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm–derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.

The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations

Nickeleit, Volker — Tue, 26 Dec 2017 06:09:47 GMT-08:00

Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1–3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.

Extracellular Adenosine Stimulates Vacuolar ATPase–Dependent Proton Secretion in Medullary Intercalated Cells

Battistone, Maria A. — Fri, 08 Dec 2017 08:43:45 GMT-08:00

Acidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration–approved drug, but very little is known about the effect of adenosine on IC function. Therefore, we investigated the role of adenosine in the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or other IC subtypes. Both receptors are located in A-IC apical membranes, and adenosine injection increased urine adenosine concentration and decreased urine pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist induced V-ATPase translocation from vesicles to the plasma membrane and increased protein kinase A (PKA)–dependent protein phosphorylation in purified medullary ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B receptors in a cAMP/PKA pathway–dependent mechanism to induce V-ATPase–dependent H+ secretion.

Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated Rejection

Viglietti, Denis — Mon, 18 Dec 2017 06:53:04 GMT-08:00

No tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (P<0.001) and presence of interstitial fibrosis/tubular atrophy (P=0.003) at diagnosis and changes in GFR (P<0.001), peritubular capillaritis Banff score (P=0.002), and DSA mean fluorescence intensity (P<0.001) after treatment. Overall, this model showed good calibration and discrimination (C-statistic=0.84). The ABMR prognostic score derived from the prediction model identified three risk strata with 6-year kidney allograft survival rates of 6.0% (high-risk group, n=40), 44.9% (intermediate-risk group, n=36), and 84.4% (low-risk group, n=202), and it provided greater net clinical benefit to patients than did considering them all to have the same level of risk of allograft loss. The performance of the ABMR prognostic score was validated in an independent cohort of 202 kidney recipients with ABMR (C-statistic=0.79). The ABMR prognostic score could be used to inform therapeutic decisions in clinical practice and for the design of clinical trials.

MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial Function

Guo, Yan — Tue, 17 Oct 2017 06:48:30 GMT-07:00

Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro. Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.

BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended Protocols

Drawz, Paul E. — Thu, 19 Oct 2017 07:00:07 GMT-07:00

Hypertension is the leading chronic disease risk factor in the world and is especially important in patients with CKD, nearly 90% of whom have hypertension. Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality. However, because BP was measured unobserved using an automated device, some investigators have questioned the ability to translate SPRINT results into routine clinical practice, in which measurement of BP is typically less standardized. In this review, we discuss the BP measurement techniques used in major observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, evaluate the effect of measurement technique on BP readings, and explore how ambulatory BP data from the SPRINT trial may inform this discussion. We conclude by arguing for implementation of guideline-recommended BP measurement techniques in routine clinical practice.

Metabolic Acidosis and Subclinical Metabolic Acidosis in CKD

Raphael, Kalani L. — Fri, 13 Oct 2017 06:12:18 GMT-07:00

Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO2 at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO2 and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.

Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease

Nowak, Kristen L. — Wed, 08 Nov 2017 06:11:36 GMT-08:00

The association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m2 who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5–24.9 kg/m2; reference; n=192), overweight (25.0–29.9 kg/m2; n=168), or obese (≥30 kg/m2; n=81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m2. The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%; P<0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (β=0.79; 95% confidence interval [95% CI], 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted β =−0.08; 95% CI, −0.15 to −0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.

Perioperative THR-184 and AKI after Cardiac Surgery

Himmelfarb, Jonathan — Mon, 04 Dec 2017 08:31:59 GMT-08:00

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.

Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I

Gunsolus, Ian — Fri, 27 Oct 2017 06:06:36 GMT-07:00

Measures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%–95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%–61% with severely impaired renal function (eGFR<30 ml/min per 1.73 m2; n=81) and 40%–41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%–57% with normal function to 27%–42% with severely impaired function and 15%–32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.

Clinical Decision Support for In-Hospital AKI

Al-Jaghbeer, Mohammed — Thu, 02 Nov 2017 02:30:09 GMT-07:00

AKI carries a significant mortality and morbidity risk. Use of a clinical decision support system (CDSS) might improve outcomes. We conducted a multicenter, sequential period analysis of 528,108 patients without ESRD before admission, from October of 2012 to September of 2015, to determine whether use of a CDSS reduces hospital length of stay and in-hospital mortality for patients with AKI. We compared patients treated 12 months before (181,696) and 24 months after (346,412) implementation of the CDSS. Coprimary outcomes were hospital mortality and length of stay adjusted by demographics and comorbidities. AKI was diagnosed in 64,512 patients (12.2%). Crude mortality rate fell from 10.2% before to 9.4% after CDSS implementation (odds ratio, 0.91; 95% confidence interval [95% CI], 0.86 to 0.96; P=0.001) for patients with AKI but did not change in patients without AKI (from 1.5% to 1.4%). Mean hospital duration decreased from 9.3 to 9.0 days (P<0.001) for patients with AKI, with no change for patients without AKI. In multivariate mixed-effects models, the adjusted odds ratio (95% CI) was 0.76 (0.70 to 0.83) for mortality and 0.66 (0.61 to 0.72) for dialysis (P<0.001). Change in adjusted hospital length of stay was also significant (incidence rate ratio, 0.91; 95% CI, 0.89 to 0.92), decreasing from 7.2 to 6.0 days for patients with AKI. Results were robust to sensitivity analyses and were sustained for the duration of follow-up. Hence, implementation of a CDSS for AKI resulted in a small but sustained decrease in hospital mortality, dialysis use, and length of stay.

Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus–Driven Hypertension in Diverse Diabetic Models

Harlan, Shannon M. — Mon, 23 Oct 2017 06:02:12 GMT-07:00

Progress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts, ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe renal lesions. In type 2 models of diabetes (C57BKLS db/db and BTBR ob/ob mice), compared with LacZAAV, ReninAAV induced significant elevations in ACR and increased the incidence and severity of histopathologic findings, with increased serum creatinine detected only in the ReninAAV-treated db/db mice. The uninephrectomized ReninAAV db/db model was the most progressive model examined and further characterized. In this model, separate treatment of hyperglycemia with rosiglitazone or hypertension with lisinopril partially reduced ACR, consistent with independent contributions of these disorders to renal disease. Microarray analysis and comparison with human DKD showed common pathways affected in human disease and this model. These results identify novel models of progressive DKD that provide researchers with a facile and reliable method to study disease pathogenesis and support the development of therapeutics.

Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRD

Mottl, Amy K. — Mon, 27 Nov 2017 06:42:39 GMT-08:00

Pathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P<0.1 were added into successively complex models. ESRD occurred in 56% of patients, and 26% of patients died before reaching ESRD. In univariate analyses, diabetic nephropathy class was not statistically significant in predicting time to ESRD. The final multivariable model (n=106) showed a borderline association between mild mesangial expansion and decreased risk for ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor prognostic factors in the final model included segmental sclerosis and extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval, 1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and extracapillary hypercellularity as novel, poor prognostic indicators of time from DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of disease severity.

Bardoxolone—the Phoenix?

Toto, Robert D. — Thu, 25 Jan 2018 06:04:03 GMT-08:00

Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic Nephropathy

Hinden, Liad — Fri, 13 Oct 2017 06:12:18 GMT-07:00

Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2 expression, affected the dynamic translocation of GLUT2 to the brush border membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and ameliorate DN. These findings may support the rationale for the clinical testing of peripherally restricted CB1R antagonists or the development of novel renal-specific GLUT2 inhibitors against DN.

Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy

Seitz-Polski, Barbara — Tue, 07 Nov 2017 08:42:44 GMT-08:00

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0.001). Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.

Chromatin Conformation Links Distal Target Genes to CKD Loci

Brandt, Maarten M. — Wed, 01 Nov 2017 06:17:44 GMT-07:00

Genome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes. To identify target genes of these DREs, we used circular chromosome conformation capture (4C) sequencing on glomerular endothelial cells and renal tubular epithelial cells. Our 4C analyses revealed interactions of CKD-associated susceptibility regions with the transcriptional start sites of 304 target genes. Overlap with multiple databases confirmed that many of these target genes are involved in kidney homeostasis. Expression quantitative trait loci analysis revealed that mRNA levels of many target genes are genotype dependent. Pathway analyses showed that target genes were enriched in processes crucial for renal function, identifying dysregulated geranylgeranyl diphosphate biosynthesis as a potential disease mechanism. Overall, our data annotated multiple genes to previously reported CKD-associated single-nucleotide polymorphisms and provided evidence for interaction between these loci and target genes. This pipeline provides a novel technique for hypothesis generation and complements classic GWAS interpretation. Future studies are required to specify the implications of our dataset and further reveal the complex roles that common variants have in complex diseases, such as CKD.

Should We Increase GFR with Bardoxolone in Alport Syndrome?

Baigent, Colin — Thu, 25 Jan 2018 06:04:05 GMT-08:00

Longitudinal FGF23 Trajectories and Mortality in Patients with CKD

Isakova, Tamara — Wed, 22 Nov 2017 07:51:13 GMT-08:00

Elevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.

Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules

Wolley, Martin — Mon, 05 Mar 2018 07:48:22 GMT-08:00

Dialysis technologies have continued to advance over recent decades; however, these advancements have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as “difficult to remove.” With a new generation of hemodialysis membranes now making meaningful clearance of these molecules possible, it is an apt time to review the clinical relevance of these middle molecules. Our review describes the developments in membrane technology that enable the removal of large middle molecules (molecular mass >15 kD) that is limited with high-flux dialysis membranes. Of the known 58 middle molecules, a literature search identified 27 that have molecular mass >15 kD. This group contains cytokines, adipokines, hormones, and other proteins. These molecules are implicated in chronic inflammation, atherosclerosis, structural heart disease, and secondary immunodeficiency in the literature. Single-center safety and efficacy studies have identified that use of these membranes in maintenance dialysis populations is associated with limited loss of albumin and increased clearance of large middle molecules. Larger, robustly conducted, multicenter studies are now evaluating these findings. After completion of these safety and efficacy studies, the perceived clinical benefits of providing clearance of large middle molecules must be assessed in rigorously conducted, randomized clinical studies.

Glucocorticoids in the Treatment of Glomerular Diseases

Ponticelli, Claudio — Fri, 23 Feb 2018 11:41:48 GMT-08:00

Glucocorticoids exert anti-inflammatory and immunosuppressive activities by genomic and nongenomic effects. The classic genomic effects are mediated by cytosolic glucocorticoid receptors that can upregulate the expression of anti-inflammatory proteins in the nucleus (transactivation) or repress the translocation of proinflammatory transcription factors from the cytosol into the nucleus (transrepression). The nongenomic effects are probably mediated by membrane glucocorticoid receptors. Glucocorticoid receptors are expressed also in podocytes and experimental data suggest that glucocorticoids may protect from podocyte injury. Glucocorticoids have a low therapeutic index and may exert a number of time-dependent and dose-dependent side effects. Measures to prevent or attenuate side effects include single-morning administration of short-acting glucocorticoids, dietetic counseling, increasing physical activity, frequent monitoring, and adapting the doses to the clinical conditions of the patient. Synthetic glucocorticoids, either given alone or in combination with other immunosuppressive drugs, are still the cornerstone therapy in multiple glomerular disorders. However, glucocorticoids are of little benefit in C3 glomerulopathy and may be potentially deleterious in patients with maladaptive focal glomerulosclerosis. Their efficacy depends not only on the type and severity of glomerular disease, but also on the timeliness of administration, the dosage, and the duration of treatment. Whereas an excessive use of glucocorticoids can be responsible for severe toxicity, too low a dosage and too short duration of glucocorticoid treatment can result in false steroid resistance.

Time-Centered Approach to Understanding Risk Factors for the Progression of CKD

Ku, Elaine — Fri, 30 Mar 2018 07:04:05 GMT-07:00

Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis

Wu, Chia-Lin — Mon, 16 Apr 2018 07:17:07 GMT-07:00

Management of Membranous Nephropathy in the PLA2R Era

Bomback, Andrew S. — Mon, 29 Jan 2018 05:14:35 GMT-08:00

Management of Severe Hyponatremia with Continuous Renal Replacement Therapies

Rosner, Mitchell H. — Tue, 20 Feb 2018 07:08:13 GMT-08:00

Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation System

Huang, Edmund — Fri, 09 Mar 2018 06:45:08 GMT-08:00

Secular Trends in Infection-Related Mortality after Kidney Transplantation

Kinnunen, Susanna — Thu, 05 Apr 2018 06:42:12 GMT-07:00

Awareness of Racial Disparities in Kidney Transplantation among Health Care Providers in Dialysis Facilities

Kim, Joyce J. — Thu, 12 Apr 2018 05:03:52 GMT-07:00

HLA-DQ Mismatching and Kidney Transplant Outcomes

Leeaphorn, Napat — Mon, 23 Apr 2018 05:36:44 GMT-07:00

Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care Unit

Hessey, Erin — Fri, 20 Apr 2018 07:37:15 GMT-07:00

Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury

Heylen, Line — Mon, 02 Apr 2018 06:38:35 GMT-07:00

Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n=13), after implantation and reperfusion (postischemia; n=13), and at 3 or 12 months after transplant (n=5 each); a cross-sectional cohort with preimplantation biopsy specimens (n=82); and a cross-sectional cohort with postreperfusion biopsy specimens (n=46). Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables. Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.

Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients

Bozic, Milica — Thu, 08 Mar 2018 10:12:42 GMT-08:00

Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration Rate

Wang, Feijie — Thu, 08 Mar 2018 10:12:41 GMT-08:00

Black Americans’ Perspectives of Barriers and Facilitators of Community Screening for Kidney Disease

Umeukeje, Ebele M. — Thu, 15 Mar 2018 06:59:34 GMT-07:00

Association of Nonoxidized Parathyroid Hormone with Cardiovascular and Kidney Disease Outcomes in Chronic Kidney Disease

Seiler-Mussler, Sarah — Mon, 05 Mar 2018 07:48:21 GMT-08:00

Transplant Center Patient Navigator and Access to Transplantation among High-Risk Population

Basu, Mohua — Mon, 26 Mar 2018 06:08:26 GMT-07:00

Association of Serious Fall Injuries among United States End Stage Kidney Disease Patients with Access to Kidney Transplantation

Plantinga, Laura C. — Tue, 06 Mar 2018 06:04:23 GMT-08:00

What Else Can We Do to Ensure Transplant Equity for High-Risk Patients?

Waterman, Amy D. — Mon, 26 Mar 2018 06:08:25 GMT-07:00

An Evolving Continuum of Care for the Kidney Disease Patient Will Help the Transplant Center Patient Navigator

Knight, Richard A. — Mon, 26 Mar 2018 06:08:25 GMT-07:00

Correlation of Urine Ammonium and Urine Osmolal Gap in Kidney Transplant Recipients

Raphael, Kalani L. — Thu, 08 Mar 2018 10:12:41 GMT-08:00

Evaluation and Management of CKD in the Nonkidney Solid Organ Transplant Recipient

Warburton, Karen M. — Thu, 11 Jan 2018 11:49:58 GMT-08:00

Fibroblast Growth Factor 23 Associates with Death in Critically Ill Patients

Leaf, David E. — Thu, 08 Mar 2018 10:12:43 GMT-08:00

Attributable Risk and Time Course of Colistin-Associated Acute Kidney Injury

Miano, Todd A. — Thu, 15 Mar 2018 06:59:35 GMT-07:00

Targeting Zero Infections in Dialysis: New Devices, Yes, but also Guidelines, Checklists, and a Culture of Safety

Kliger, Alan S. — Mon, 05 Mar 2018 07:48:41 GMT-08:00

Evaluation of Potential Living Kidney Donors in the APOL1 Era

Freedman, Barry I. — Fri, 09 Mar 2018 06:45:32 GMT-08:00

We AIM2 Inflame

Linkermann, Andreas — Tue, 06 Mar 2018 06:04:32 GMT-08:00

Gender Disparities and Financial Barriers to Living Kidney Donation

Matas, Arthur J. — Thu, 08 Mar 2018 10:12:55 GMT-08:00

Wnt9a Promotes Renal Fibrosis by Accelerating Cellular Senescence in Tubular Epithelial Cells

Luo, Congwei — Mon, 12 Feb 2018 11:24:00 GMT-08:00

Cellular senescence is associated with renal disease progression, and accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis. However, the underlying mechanism is unknown. We assessed the potential role of Wnt9a in tubular cell senescence and renal fibrosis. Compared with tubular cells of normal subjects, tubular cells of humans with a variety of nephropathies and those of several mouse models of CKD expressed high levels of Wnt9a that colocalized with the senescence-related protein p16INK4A. Wnt9a expression level correlated with the extent of renal fibrosis, decline of eGFR, and expression of p16INK4A. Furthermore, ectopic expression of Wnt9a after ischemia-reperfusion injury (IRI) induced activation of β-catenin and exacerbated renal fibrosis. Overexpression of Wnt9a exacerbated tubular senescence, evidenced by increased detection of p16INK4A expression and senescence-associated β-galactosidase activity. Conversely, shRNA-mediated knockdown of Wnt9a repressed IRI-induced renal fibrosis in vivo and impeded the growth of senescent tubular epithelial cells in culture. Notably, Wnt9a-induced renal fibrosis was inhibited by shRNA-mediated silencing of p16INK4A in the IRI mouse model. In a human proximal tubular epithelial cell line and primary renal tubular cells, Wnt9a remarkably upregulated levels of senescence-related p16INK4A, p19ARF, p53, and p21 and decreased the phosphorylation of retinoblastoma protein. Wnt9a also induced senescent tubular cells to produce TGF-β1, which promoted proliferation and activation in normal rat kidney fibroblasts. Thus, Wnt9a drives tubular senescence and fibroblast activation. Furthermore, the Wnt9a–TGF-β pathway appears to create a reciprocal activation loop between senescent tubular cells and activated fibroblasts that promotes and accelerates the pathogenesis of renal fibrosis.

Macrophage Uptake of Necrotic Cell DNA Activates the AIM2 Inflammasome to Regulate a Proinflammatory Phenotype in CKD

Komada, Takanori — Fri, 09 Feb 2018 06:41:55 GMT-08:00

Nonmicrobial inflammation contributes to CKD progression and fibrosis. Absent in melanoma 2 (AIM2) is an inflammasome-forming receptor for double-stranded DNA. AIM2 is expressed in the kidney and activated mainly by macrophages. We investigated the potential pathogenic role of the AIM2 inflammasome in kidney disease. In kidneys from patients with diabetic or nondiabetic CKD, immunofluorescence showed AIM2 expression in glomeruli, tubules, and infiltrating leukocytes. In a mouse model of unilateral ureteral obstruction (UUO), Aim2 deficiency attenuated the renal injury, fibrosis, and inflammation observed in wild-type (WT) littermates. In bone marrow chimera studies, UUO induced substantially more tubular injury and IL-1β cleavage in Aim2−/− or WT mice that received WT bone marrow than in WT mice that received Aim2−/− bone marrow. Intravital microscopy of the kidney in LysM(gfp/gfp) mice 5–6 days after UUO demonstrated the significant recruitment of GFP+ proinflammatory macrophages that crawled along injured tubules, engulfed DNA from necrotic cells, and expressed active caspase-1. DNA uptake occurred in large vacuolar structures within recruited macrophages but not resident CX3CR1+ renal phagocytes. In vitro, macrophages that engulfed necrotic debris showed AIM2-dependent activation of caspase-1 and IL-1β, as well as the formation of AIM2+ ASC specks. ASC specks are a hallmark of inflammasome activation. Cotreatment with DNaseI attenuated the increase in IL-1β levels, confirming that DNA was the principal damage-associated molecular pattern in this process. Therefore, the activation of the AIM2 inflammasome by DNA from necrotic cells drives a proinflammatory phenotype that contributes to chronic injury in the kidney.

Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging

Chung, Ki Wung — Mon, 12 Feb 2018 11:23:59 GMT-08:00

Defects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator–activated receptor α (PPARα) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPARα and the FAO pathway–associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPARα protein expression associated with increased expression of PPARα-targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPARα expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF-β–induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPARα−/− mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPARα signaling during aging aggravates renal fibrosis development, and targeting PPARα is useful for preventing age-associated CKD.

The Change in Living Kidney Donation in Women and Men in the United States (2005–2015): A Population-Based Analysis

Gill, Jagbir — Thu, 08 Mar 2018 10:12:55 GMT-08:00

The factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men.

NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic Acidosis

Lee, Hyun-Wook — Mon, 26 Feb 2018 07:11:48 GMT-08:00

Renal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered. Additionally, NBCe1-A deletion almost completely blocked the ability to increase ammonia excretion after exogenous acid loading. Under basal conditions and during acid loading, urine pH was more acidic in mice with NBCe1-A deletion than in wild-type controls, indicating that the abnormal ammonia excretion was not caused by a primary failure of urine acidification. Instead, NBCe1-A deletion altered the expression levels of multiple enzymes involved in proximal tubule ammonia generation, including phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and glutamine synthetase, under basal conditions and after exogenous acid loading. Deletion of NBCe1-A did not impair expression of key proteins involved in collecting duct ammonia secretion. These studies demonstrate that the integral membrane protein NBCe1-A has a critical role in basal and acidosis-stimulated ammonia metabolism through the regulation of proximal tubule ammonia-metabolizing enzymes.

APOL1 Genotype and Renal Function of Black Living Donors

Doshi, Mona D. — Tue, 16 Jan 2018 06:24:50 GMT-08:00

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular Inflammation

Krohn, Sonja — Mon, 26 Feb 2018 07:11:49 GMT-08:00

The IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E). In mouse models of crescentic GN (nephrotoxic nephritis) and pristane-induced lupus nephritis, deficiency in IL-17C significantly ameliorated the course of GN in terms of renal tissue injury and kidney function. Deficiency of the unique IL-17C receptor IL-17 receptor E (IL-17RE) provided similar protection against crescentic GN. These protective effects associated with a reduced TH17 response. Bone marrow transplantation experiments revealed that IL-17C is produced by tissue-resident cells, but not by lymphocytes. Finally, IL-17RE was highly expressed by CD4+ TH17 cells, and loss of this expression prevented the TH17 responses and subsequent tissue injury in crescentic GN. Our findings indicate that IL-17C promotes TH17 cell responses and immune-mediated kidney disease via IL-17RE expressed on CD4+ TH17 cells. Targeting the IL-17C/IL-17RE pathway may present an intriguing therapeutic strategy for TH17-induced autoimmune disorders.

Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an Alarmin

Ferhat, Maroua — Wed, 07 Feb 2018 06:14:32 GMT-08:00

Inflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33Gt/Gt) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-γ/IL-17A–producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33–specific receptor, on the surface of iNKT cells preceded the IL-33– and iNKT cell–dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells in vitro, inducing IFN-γ and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.

Unique Gene Expression in Developing Ascending Vasa Recta: A Tale of Tie

Basile, David P. — Mon, 12 Mar 2018 05:59:02 GMT-07:00

This Month’s Highlights

American Society of Nephrology — Fri, 30 Mar 2018 01:00:46 GMT-07:00

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients

Polinder-Bos, Harmke A. — Thu, 01 Mar 2018 10:55:01 GMT-08:00

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography–computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, −4.1 ml/100 g per minute; 95% confidence interval, −7.3 to −0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.

Maintenance and Breakdown of Glomerular Tuft Architecture

Kriz, Wilhelm — Tue, 13 Mar 2018 06:18:15 GMT-07:00

Protein Kinase 2β Is Expressed in Neural Crest-Derived Urinary Pacemaker Cells and Required for Pyeloureteric Contraction

Iskander, Samir M. — Wed, 07 Feb 2018 06:14:32 GMT-08:00

Nonobstructive hydronephrosis, defined as dilatation of the renal pelvis with or without dilatation of the ureter, is the most common antenatal abnormality detected by fetal ultrasound. Yet, the etiology of nonobstructive hydronephrosis is poorly defined. We previously demonstrated that defective development of urinary tract pacemaker cells (utPMCs) expressing hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) and the stem cell marker cKIT causes abnormal ureteric peristalsis and nonobstructive hydronephrosis. However, further investigation of utPMC development and function is limited by lack of knowledge regarding the embryonic derivation, development, and molecular apparatus of these cells. Here, we used lineage tracing in mice to identify cells that give rise to utPMCs. Neural crest cells (NCCs) indelibly labeled with tdTomato expressed HCN3 and cKIT. Furthermore, purified HCN3+ and cKIT+ utPMCs were enriched in Sox10 and Tfap-2α, markers of NCCs. Sequencing of purified RNA from HCN3+ cells revealed enrichment of a small subset of RNAs, including RNA encoding protein kinase 2β (PTK2β), a Ca2+-dependent tyrosine kinase that regulates ion channel activity in neurons. Immunofluorescence analysis in situ revealed PTK2β expression in NCCs as early as embryonic day 12.5 and in HCN3+ and cKIT+ utPMCs as early as embryonic day 15.5, with sustained expression in HCN3+ utPMCs until postnatal week 8. Pharmacologic inhibition of PTK2β in murine pyeloureteral tissue explants inhibited contraction frequency. Together, these results demonstrate that utPMCs are derived from NCCs, identify new markers of utPMCs, and demonstrate a functional contribution of PTK2β to utPMC function.

Effect of Bariatric Surgery on CKD Risk

Friedman, Allon N. — Mon, 15 Jan 2018 09:38:15 GMT-08:00

Obesity is linked to the development and progression of CKD, but whether bariatric surgery protects against CKD is poorly understood. We, therefore, examined whether bariatric surgery influences CKD risk. The study included 2144 adults who underwent bariatric surgery from March of 2006 to April of 2009 and participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort. The primary outcome was CKD risk categories as assessed by the Kidney Disease Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR and albuminuria. Patients were 79% women and 87% white, with a median age of 46 years old. Improvements were observed in CKD risk at 1 and 7 years after surgery in patients with moderate baseline CKD risk (63% and 53%, respectively), high baseline risk (78% and 56%, respectively), and very high baseline risk (59% and 23%, respectively). The proportion of patients whose CKD risk worsened was ≤10%; five patients developed ESRD. Sensitivity analyses using year 1 as baseline to minimize the effect of weight loss on serum creatinine and differing eGFR equations offered qualitatively similar results. Treatment with bariatric surgery associated with an improvement in CKD risk categories in a large proportion of patients for up to 7 years, especially in those with moderate and high baseline risk. These findings support consideration of CKD risk in evaluation for bariatric surgery and further study of bariatric surgery as a treatment for high-risk obese patients with CKD.

Nephronectin Regulates Mesangial Cell Adhesion and Behavior in Glomeruli

Zimmerman, Susan E. — Mon, 15 Jan 2018 09:38:16 GMT-08:00

A critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin (Npnt), a GBM component and known ligand of α8β1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of Npnt from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with α8β1 integrin to novel, specialized adhesion structures that occurred at sites of mesangial cell protrusion at the base of the capillary loops. Absence of nephronectin disrupted these adhesion structures, leading to mislocalization of α8β1. Podocyte-specific deletion of Npnt also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and α8β1 integrin in a newly described adhesion complex and begin to uncover the molecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states.

Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection

Brunelli, Steven M. — Thu, 22 Feb 2018 07:39:40 GMT-08:00

Central venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing >183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates (P=0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.

The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor with Therapeutic Potential

Michelfelder, Stefan — Mon, 15 Jan 2018 09:38:14 GMT-08:00

The complement system is essential for host defense, but uncontrolled complement system activation leads to severe, mostly renal pathologies, such as atypical hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel combinational approach to modulate complement activation by targeting C3 and the terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the regulatory domains of complement factor H (FH) with the C5 convertase/C5b-9 inhibitory fragment of the FH-related protein 1. In vitro, MFHR1 showed cofactor and decay acceleration activity and inhibited C5 convertase activation and C5b-9 assembly, which prevented C3b deposition and reduced C3a/C5a and C5b-9 generation. Furthermore, this fusion protein showed the ability to escape deregulation by FH-related proteins and form multimeric complexes with increased inhibitory activity. In addition to substantially inhibiting alternative and classic pathway activation, MFHR1 blocked hemolysis mediated by serum from a patient with aHUS expressing truncated FH. In FH−/− mice, MFHR1 administration augmented serum C3 levels, reduced abnormal glomerular C3 deposition, and ameliorated C3 glomerulopathy. Taking the unique design of MFHR1 into account, we suggest that the combination of proximal and terminal cascade inhibition together with the ability to form multimeric complexes explain the strong inhibitory capacity of MFHR1, which offers a novel basis for complement therapeutics.

Ascending Vasa Recta Are Angiopoietin/Tie2-Dependent Lymphatic-Like Vessels

Kenig-Kozlovsky, Yael — Wed, 13 Dec 2017 07:17:02 GMT-08:00

Urinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by a countercurrent multiplication mechanism. Medullary hyperosmolarity is protected from washout by countercurrent exchange and efficient removal of interstitial fluid resorbed from the loop of Henle and collecting ducts. In most tissues, lymphatic vessels drain excess interstitial fluid back to the venous circulation. However, the renal medulla is devoid of classic lymphatics. Studies have suggested that the fenestrated ascending vasa recta (AVRs) drain the interstitial fluid in this location, but this function has not been conclusively shown. We report that late gestational deletion of the angiopoietin receptor endothelial tyrosine kinase 2 (Tie2) or both angiopoietin-1 and angiopoietin-2 prevents AVR formation in mice. The absence of AVR associated with rapid accumulation of fluid and cysts in the medullary interstitium, loss of medullary vascular bundles, and decreased urine concentrating ability. In transgenic reporter mice with normal angiopoietin-Tie2 signaling, medullary AVR exhibited an unusual hybrid endothelial phenotype, expressing lymphatic markers (prospero homeobox protein 1 and vascular endothelial growth factor receptor 3) as well as blood endothelial markers (CD34, endomucin, platelet endothelial cell adhesion molecule 1, and plasmalemmal vesicle–associated protein). Taken together, our data redefine the AVRs as Tie2 signaling–dependent specialized hybrid vessels and provide genetic evidence of the critical role of AVR in the countercurrent exchange mechanism and the structural integrity of the renal medulla.

Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection

Kolb, Alexander L. — Thu, 25 Jan 2018 06:04:04 GMT-08:00

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P<0.05) observed in controls and increased the mitochondria membrane potential (P<0.05), maximal respiratory capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning.

Fibroblast-Specific β-Catenin Signaling Dictates the Outcome of AKI

Zhou, Dong — Wed, 17 Jan 2018 06:23:40 GMT-08:00

AKI is a devastating condition with high morbidity and mortality. The pathologic features of AKI are characterized by tubular injury, inflammation, and vascular impairment. Whether fibroblasts in the renal interstitium have a role in the pathogenesis of AKI is unknown. In this study, we investigated the role of fibroblast-specific β-catenin signaling in dictating the outcome of AKI, using conditional knockout mice in which β-catenin was specifically ablated in fibroblasts (Gli1-β-cat−/−). After ischemia-reperfusion injury (IRI), Gli1-β-cat−/− mice had lower serum creatinine levels and less morphologic injury than Gli1-β-cat+/+ littermate controls. Moreover, we detected fewer apoptotic cells, as well as decreased cytochrome C release; reduced expression of Bax, FasL, and p53; and increased phosphorylation of Akt, in the Gli1-β-cat−/− kidneys. Gli1-β-cat−/− kidneys also exhibited upregulated expression of proliferating cell nuclear antigen and Ki-67, which are markers of cell proliferation. Furthermore, Gli1-β-cat−/− kidneys displayed suppressed NF-κB signaling and cytokine expression and reduced infiltration of inflammatory cells. Notably, loss of β-catenin in fibroblasts induced renal expression of hepatocyte growth factor (HGF) and augmented the tyrosine phosphorylation of c-met receptor after IRI. In vitro, treatment with Wnt ligands or ectopic expression of active β-catenin inhibited HGF mRNA and protein expression and repressed HGF promoter activity. Collectively, these results suggest that fibroblast-specific β-catenin signaling can control tubular injury and repair in AKI by modulating HGF expression. Our studies uncover a previously unrecognized role for interstitial fibroblasts in the pathogenesis of AKI.

The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes

Kim, Yaeni — Fri, 12 Jan 2018 07:47:04 GMT-08:00

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor–α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase–β (CaMKKβ) and numbers of phosphorylated liver kinase B1 (LKB1)– and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKKβ, phosphorylated Ser431LKB1, phosphorylated Thr172AMPK, and PPARα expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose–treated human GECs and murine podocytes, AdipoRon increased intracellular Ca2+ levels that activated a CaMKKβ/phosphorylated Ser431LKB1/phosphorylated Thr172AMPK/PPARα pathway and downstream signaling, thus decreasing high-glucose–induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.

Filtering the Evidence: Is There a Cognitive Cost of Hemodialysis?

Wolfgram, Dawn F. — Thu, 01 Mar 2018 10:55:02 GMT-08:00

Bariatric Surgery and Kidney Health

Lieske, John C. — Mon, 12 Mar 2018 05:59:03 GMT-07:00

Blood HER2 and Uromodulin as Causal Mediators of CKD

Sjaarda, Jennifer — Tue, 06 Mar 2018 06:04:33 GMT-08:00

Many biomarkers have been epidemiologically linked with CKD; however, the possibility that such associations are due to reverse causation or confounding limits the utility of these biomarkers. To overcome this limitation, we used a Mendelian randomization (MR) approach to identify causal mediators of CKD. We performed MR by first identifying genetic determinants of 227 serum protein biomarkers assayed in 4147 participants of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial who had early or prediabetes, and assessing the effects of these biomarkers on CKD in the CKD genetics consortium (n=117,165; 12,385 cases) using the inverse-variance weighted (fixed-effects) method. We then estimated the relationship between the serum concentration of each biomarker identified and incident CKD in ORIGIN participants. MR identified uromodulin (UMOD) and human EGF receptor 2 (HER2) as novel, causal mediators of CKD (UMOD: odds ratio [OR], 1.30 per SD; 95% confidence interval [95% CI], 1.25 to 1.35; P<5×10−20; HER2: OR, 1.30 per SD; 95% CI, 1.14 to 1.48; P=8.0×10−5). Consistent with these findings, blood HER2 concentration associated with CKD events in ORIGIN participants (OR, 1.07 per SD; 95% CI, 1.01 to 1.13; P=0.01). Additional exploratory MR analyses identified angiotensin-converting enzyme (ACE) as a regulator of HER2 levels (β=0.13 per SD; 95% CI, 0.08 to 0.16; P=2.5×10−7). This finding was corroborated by an inverse relationship between ACE inhibitor use and HER2 levels. Thus, UMOD and HER2 are independent causal mediators of CKD in humans, and serum HER2 levels are regulated in part by ACE. These biomarkers are potential therapeutic targets for CKD prevention.

HIV-Positive Kidney Donor Selection for HIV-Positive Transplant Recipients

Muller, Elmi — Fri, 12 Jan 2018 07:47:04 GMT-08:00

The risks associated with transplanting HIV-positive kidneys into HIV-positive recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to trauma. The average age for donors was 34 (interquartile range, 19–52) years old. In some donors, only one kidney was used because of a limited number of suitable recipients on the waiting list. Only two donors had been previously exposed to antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status was not known before the time of death. Initial concerns about transplanting HIV-positive allografts into HIV-positive recipients in this clinic revolved around the possibility of HIV superinfection. However, all recipients remained virally suppressed several years after the transplant. Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication. After counseling and improved compliance, the viral load decreased and became suppressed again. Herein, we discuss the findings of this study and review the literature available on this crucial topic.

ApoL1 Overexpression Drives Variant-Independent Cytotoxicity

O'Toole, John F. — Mon, 27 Nov 2017 06:42:42 GMT-08:00

Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1-dependent currents with whole-cell patch clamping. Neither reference nor variant APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, and -G2 inserted into the plasma membrane and formed pH-sensitive cation channels, causing collapse of cellular Na+ and K+ gradients, phosphorylation of p38 mitogen-activated protein kinase, and cell death, without variant-dependent differences. APOL1-G0 and -G2 exhibited similar channel properties in whole-cell patch clamp experiments. At low expression levels, neither reference nor variant APOL1s localized on the plasma membrane, Na+ and K+ gradients were maintained, and cells remained viable. Our results indicate that APOL1-mediated pore formation is critical for the trypanolytic activity of APOL1 and drives APOL1-mediated cytotoxicity in overexpression systems. The absence of cytotoxicity at physiologic expression levels suggests variant-dependent intracellular K+ loss and cytotoxicity does not drive kidney disease progression.

The Era of Human Developmental Nephrology

Nishinakamura, Ryuichi — Thu, 15 Feb 2018 11:05:40 GMT-08:00

This Month’s Highlights

American Society of Nephrology — Wed, 28 Feb 2018 01:00:48 GMT-08:00

Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport Syndrome

Funk, Steven D. — Wed, 20 Dec 2017 07:39:15 GMT-08:00

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3−/− mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5+/− females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α3α4α5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.

Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling

Santana Machado, Tacy — Fri, 08 Dec 2017 08:43:46 GMT-08:00

In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters. This effect depended on the aryl hydrocarbon receptor pathway. Presence of human albumin at physiologic concentration in the culture medium did not abolish the effect of IS. In two mouse models of CKD, the decline in renal function associated with the accumulation of IS in serum and the specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or kidney transplant recipients with CKD, those with higher serum levels of IS needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin target blood concentration. This need associated with serum levels of IS independent of renal function. These findings suggest that increased activity of P-gp could be responsible for increased hepatic cyclosporin clearance. Altogether, these results suggest that uremic toxins, such as IS, through effects on drug transporters, may modify the nonrenal clearance of drugs in patients with CKD.

Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney

Micanovic, Radmila — Mon, 27 Nov 2017 06:42:41 GMT-08:00

Tamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP−/− mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP−/− mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP−/− mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP−/− mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI.

Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury

Cao, Qi — Tue, 02 Jan 2018 09:07:55 GMT-08:00

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.

Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney

Lindström, Nils O. — Thu, 15 Feb 2018 11:05:40 GMT-08:00

Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2, are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs.

Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation

Lv, Lin-Li — Tue, 02 Jan 2018 09:07:53 GMT-08:00

Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.

Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning

Lindström, Nils O. — Thu, 15 Feb 2018 11:05:41 GMT-08:00

The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge—critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and rat models that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.

Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas

Martinez, Laisel — Tue, 02 Jan 2018 09:07:54 GMT-08:00

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population’s median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.

Causes of Death after a Hospitalization with AKI

Silver, Samuel A. — Thu, 14 Dec 2017 06:26:49 GMT-08:00

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.

Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion

Hoshi, Masato — Thu, 11 Jan 2018 11:50:12 GMT-08:00

The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCγ docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo. Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.

CHIP Regulates Aquaporin-2 Quality Control and Body Water Homeostasis

Wu, Qi — Thu, 14 Dec 2017 06:26:48 GMT-08:00

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2. CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling.

Acidosis and Deafness in Patients with Recessive Mutations in FOXI1

Enerbäck, Sven — Thu, 14 Dec 2017 06:26:49 GMT-08:00

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.

Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans

Kolachalama, Vijaya B. — Wed, 17 Jan 2018 06:23:41 GMT-08:00

Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute–AHR–TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2–3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.

Evolution and Kidney Development: A Rosetta Stone for Nephrology

Chevalier, Robert L. — Thu, 15 Feb 2018 11:05:41 GMT-08:00

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout

Boscardin, Emilie — Thu, 25 Jan 2018 06:04:05 GMT-08:00

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βΕΝaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that γENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in γENaC-deficient mice.

Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives

Schrezenmeier, Eva — Thu, 11 Jan 2018 11:50:12 GMT-08:00

The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.

Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome

Gaggl, Martina — Wed, 27 Dec 2017 06:38:23 GMT-08:00

Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1–4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.

Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI

Meersch, Melanie — Fri, 01 Dec 2017 06:02:23 GMT-08:00

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P< 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, −19.6%; 95% CI, −32.0% to −7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, −34.8%; 95% CI, −54.6% to −15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.

Magnesium and Risk of Hip Fracture among Patients Undergoing Hemodialysis

Sakaguchi, Yusuke — Thu, 30 Nov 2017 06:22:04 GMT-08:00

Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1–Q4, respectively; P<0.001 for trend). The range of serum magnesium levels (in milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4–2.6; Q3, 2.7–2.8, and Q4, >2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability weighting analysis showed an increased risk of hip fracture among patients in the lower magnesium quartiles. We did not observe significant effect modifications in subgroup analyses. The population-attributable fraction of serum magnesium level for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%), which was much higher than that of serum calcium, serum phosphate, and parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower risk of hip fracture among patients undergoing hemodialysis.

Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?

Kleta, Robert — Wed, 13 Dec 2017 07:17:03 GMT-08:00

Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle’s loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

De Vriese, An S. — Wed, 10 Jan 2018 06:48:09 GMT-08:00

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.

The Benefits of Tubular Proteinuria: An Evolutionary Perspective

Simons, Matias — Thu, 25 Jan 2018 06:04:04 GMT-08:00

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis

Lindström, Nils O. — Thu, 15 Feb 2018 11:05:42 GMT-08:00

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4–23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.

The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease

Devuyst, Olivier — Mon, 27 Nov 2017 06:42:41 GMT-08:00

The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in UMOD are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the UMOD paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.

GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation

Hinze, Christian — Wed, 13 Dec 2017 07:17:06 GMT-08:00

Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct–specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction–associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.

Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction

Furini, Giulia — Tue, 30 Jan 2018 07:20:49 GMT-08:00

Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.

Person-Centered Integrated Care for Chronic Kidney Disease

Valentijn, Pim P. — Fri, 09 Feb 2018 06:41:42 GMT-08:00

Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy

Avasare, Rupali S. — Thu, 11 Jan 2018 11:49:59 GMT-08:00

An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis

Troost, Jonathan P. — Wed, 22 Nov 2017 07:50:17 GMT-08:00

Diagnosis and Treatment of Intradialytic Hypotension in Maintenance Hemodialysis Patients

McIntyre, Christopher W. — Fri, 02 Feb 2018 06:08:05 GMT-08:00

Crafting the Prescription for Patients Starting Peritoneal Dialysis

Teitelbaum, Isaac — Tue, 30 Jan 2018 07:17:34 GMT-08:00

Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk

Leibler, Claire — Wed, 10 Jan 2018 06:48:10 GMT-08:00

Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated. Here, we analyzed the effect of Belatacept on different steps of the B cell–mediated response in humans. In vitro, Belatacept reduced plasmablast differentiation, Ig production, and the expression of the major transcription factor involved in plasma cell function, Blimp-1, in a T cell–independent manner. Moreover, Belatacept induced activation of the STAT3 transcription factor in stimulated B cells and reduced the expression of CD86. Additionally, Belatacept blocked CD28-mediated activation of T follicular helper cells (Tfhs) in an autologous Tfh-memory B cells model. We then validated these observations in KTRs treated with Belatacept, who had a reduced proportion of blood effector B cells and activated Tfh (PD1+ICOS+) compared with control-treated KTRs. Our in vitro and in vivo results suggest that Belatacept modulates B cell function directly and at the level of B cell-Tfh interaction. These mechanisms likely account for the optimal control of humoral responses observed in KTRs treated with Belatacept.

Left Ventricular Assist Devices and the Kidney

Ross, Daniel W. — Wed, 25 Oct 2017 05:57:25 GMT-07:00

Left ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR. In this review, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience. In light of the growing number of patients using LVADs as a destination therapy, it is important to understand the effect of these devices on the kidney. Additional research and long-term data are required to better understand the relationship between the LVAD and the kidney.

Association between Urine Ammonium and Urine TGF-β1 in CKD

Raphael, Kalani L. — Thu, 16 Nov 2017 06:49:10 GMT-08:00

Nondepressive Psychosocial Factors and CKD Outcomes in Black Americans

Lunyera, Joseph — Wed, 03 Jan 2018 06:33:22 GMT-08:00

Medication Therapy Management after Hospitalization in CKD

Tuttle, Katherine R. — Tue, 02 Jan 2018 10:59:16 GMT-08:00

Standardized Transplantation Referral Ratio to Assess Performance of Transplant Referral among Dialysis Facilities

Paul, Sudeshna — Thu, 25 Jan 2018 06:03:52 GMT-08:00

Accountability of Dialysis Facilities in Transplant Referral

Fowler, Kevin John — Thu, 25 Jan 2018 06:03:51 GMT-08:00

A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant Recipients

Puttarajappa, Chethan M. — Thu, 12 Oct 2017 06:36:24 GMT-07:00

Sepsis-Associated AKI

Prowle, J.R. — Wed, 25 Oct 2017 05:57:26 GMT-07:00

Diabetic Kidney Disease

Tong, Lili — Wed, 18 Oct 2017 06:20:27 GMT-07:00

The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated Vasculitis

Rhee, Rennie L. — Thu, 25 Jan 2018 06:03:52 GMT-08:00

Thrombotic Microangiopathy and the Kidney

Brocklebank, Vicky — Tue, 17 Oct 2017 06:48:10 GMT-07:00

Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.

Mesangial C4d Deposits in Early IgA Nephropathy

Segarra, Alfons — Thu, 16 Nov 2017 06:49:11 GMT-08:00

Correction

American Society of Nephrology — Fri, 12 Jan 2018 07:46:38 GMT-08:00

Employment among Patients Starting Dialysis in the United States

Erickson, Kevin F. — Thu, 18 Jan 2018 07:19:29 GMT-08:00

Re-Evaluation of the Normal Range of Serum Total CO2 Concentration

Kraut, Jeffrey A. — Tue, 16 Jan 2018 06:07:30 GMT-08:00

A reliable determination of blood pH, PCO2, and [HCO3−] is necessary for assessing the acid-base status of a patient. However, most acid-base disorders are first recognized through abnormalities in serum total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3−]. In screening patients on the basis of serum [TCO2], we have been concerned about the wide limits of normal for serum [TCO2], 10–13 mEq/L, reported by many clinical laboratories. Indeed, we have encountered patients with serum [TCO2] values within the lower or upper end of the normal range of the reporting laboratory, who subsequently were shown to have a cardinal acid-base disorder. Here, we present a patient who had a serum [TCO2] within the lower end of the normal range of the clinical laboratory, which resulted in delayed diagnosis of a clinically important “hidden” acid-base disorder. To better define the appropriate limits of normal for serum [TCO2], we derived the expected normal range in peripheral venous blood in adults at sea level from carefully conducted acid-base studies. We then compared this range, 23 to 30 mEq/L, to that reported by 64 clinical laboratories, 2 large commercial clinical laboratories, and the major textbook of clinical chemistry. For the most part, the range in the laboratories we queried was substantially different than that we derived and that published in the textbook, with some laboratories reporting values as low as 18–20 mEq/L and as high as 33–35 mEq/L. We conclude that the limits of values of serum [TCO2] reported by clinical laboratories are very often inordinately wide and not consistent with the range of normal expected in healthy individuals at sea level. We suggest that the limits of normal of serum [TCO2] at sea level be tightened to 23–30 mEq/L. Such correction will ensure recognition of the majority of “hidden” acid-base disorders.

The Urine Anion Gap in Context

Batlle, Daniel — Mon, 08 Jan 2018 06:19:35 GMT-08:00

Urine Anion Gap to Predict Urine Ammonium and Related Outcomes in Kidney Disease

Raphael, Kalani L. — Thu, 02 Nov 2017 07:40:19 GMT-07:00

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation

Gallon, Lorenzo — Thu, 30 Nov 2017 06:22:04 GMT-08:00

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell– and B cell–mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways.

A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection

Eskandary, Farsad — Thu, 14 Dec 2017 06:26:50 GMT-08:00

Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)–positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, −4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.

Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment

Lefaucheur, Carmen — Tue, 17 Oct 2017 06:48:30 GMT-07:00

Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.

Editorial Note: From Both Sides Now

Briggs, Josephine P. — Thu, 25 Jan 2018 06:04:05 GMT-08:00

Clinical Translation of Mesenchymal Stromal Cell Therapies in Nephrology

Perico, Norberto — Thu, 30 Nov 2017 06:22:03 GMT-08:00

Mesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell–based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.

Suppression of microRNA Activity in Kidney Collecting Ducts Induces Partial Loss of Epithelial Phenotype and Renal Fibrosis

Hajarnis, Sachin — Wed, 11 Oct 2017 08:23:23 GMT-07:00

microRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. The physiologic function of these noncoding RNAs in postnatal renal tubules still remains unclear. Surprisingly, they appear to be dispensable for mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA suppression in collecting ducts (CDs). To conclusively evaluate the role of miRNAs, we generated three mouse models with CD-specific inactivation of key miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2, 3, and 4). Characterization of these three mouse models revealed that inhibition of miRNAs in CDs spontaneously evokes a renal tubule injury–like response, which culminates in progressive tubulointerstitial fibrosis (TIF) and renal failure. Global miRNA profiling of microdissected renal tubules showed that miRNAs exhibit segmental distribution along the nephron and CDs. In particular, the expression of miR-200c is nearly 70-fold higher in CDs compared with PTs. Accordingly, miR-200s are downregulated in Dicer-KO CDs, its direct target genes Zeb1, Zeb2, and Snail2 are upregulated, and miRNA-depleted CDs undergo partial epithelial-to-mesenchymal transition (EMT). Thus, miRNAs are essential for CD homeostasis. Downregulation of CD-enriched miRNAs and the subsequent induction of partial EMT may be a new mechanism for TIF progression.

Making the Right Decision: Do Clinical Decision Support Systems for AKI Improve Patient Outcomes?

Selby, Nicholas M. — Mon, 15 Jan 2018 09:38:16 GMT-08:00

Reduced Expression of Glutathione S-Transferase α4 Promotes Vascular Neointimal Hyperplasia in CKD

Luo, Jinlong — Fri, 10 Nov 2017 10:49:37 GMT-08:00

Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)–mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE–induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE–induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.

Deletion Variants of CFHR1 and CFHR3 Associate with Mesangial Immune Deposits but Not with Progression of IgA Nephropathy

Jullien, Perrine — Tue, 07 Nov 2017 08:42:45 GMT-08:00

Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H–related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of CFHR3 and CFHR1 gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients’ medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for CFHR3,1Δ. We did not detect an association between CFHR3,1Δ and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, CFHR3,1Δ did not associate with progression to stage 3 CKD or renal death. In conclusion, the CFHR3,1Δ genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.

Redirecting TGF-β Signaling through the β-Catenin/Foxo Complex Prevents Kidney Fibrosis

Qiao, Xi — Mon, 27 Nov 2017 06:42:40 GMT-08:00

TGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β. In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity. Moreover, the level of β-catenin expression positively correlated with the level of Foxo1 binding to the Foxp3 promoter and Foxo transcriptional activity. T cell fate mapping in Foxp3gfp Ly5.1/5.2 mice revealed that coadministration of rhTGF-β1 and ICG-001 further enhanced the expansion of iTregs and natural Tregs observed with rhTGF-β1 treatment alone. Coadministration of rhTGF-β1 with ICG-001 also increased the number of Tregs and reduced inflammation and fibrosis in the kidney fibrosis models of unilateral ureteric obstruction and ischemia-reperfusion injury. Notably, ICG-001 prevented the fibrosis in distant organs (lung and liver) caused by rhTGF-β1. Together, our results show that diversion of β-catenin from TCF- to Foxo-mediated transcription inhibits the β-catenin/TCF–mediated profibrotic effects of TGF-β while enhancing the β-catenin/Foxo–mediated anti-inflammatory effects. Targeting β-catenin/Foxo may be a novel therapeutic strategy in the treatment of fibrotic diseases that lead to organ failure.

LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody Disease

Larsen, Christopher P. — Thu, 26 Oct 2017 06:38:19 GMT-07:00

Primary renal tubulointerstitial disease resulting from proximal tubule antigen–specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.

Erratum

American Society of Nephrology — Wed, 31 Jan 2018 01:00:50 GMT-08:00

This Month’s Highlights

American Society of Nephrology — Wed, 31 Jan 2018 01:00:50 GMT-08:00

Tonicity-Responsive Enhancer-Binding Protein Mediates Hyperglycemia-Induced Inflammation and Vascular and Renal Injury

Choi, Soo Youn — Mon, 20 Nov 2017 04:50:38 GMT-08:00

Diabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing in mind the paucity of effective treatment for DN and progressive CKD, novel targets for treatment are sorely needed. We previously reported that increased activity of tonicity-responsive enhancer-binding protein (TonEBP) in monocytes was associated with early DN in humans. We now extend these findings by testing the hypotheses that TonEBP in macrophages promotes hyperglycemia-mediated proinflammatory activation and chronic renal inflammation leading to DN and CKD, and TonEBP genetic variability in humans is associated with inflammatory, renal, and vascular function–related phenotypes. In a mouse model of DN, compared with the wild-type phenotype, TonEBP haplodeficiency associated with reduced activation of macrophages by hyperglycemia, fewer macrophages in the kidney, lower renal expression of proinflammatory genes, and attenuated DN. Furthermore, in a cohort of healthy humans, genetic variants within TonEBP associated with renal function, BP, and systemic inflammation. One of the genetic variants associated with renal function was replicated in a large population-based cohort. These findings suggest that TonEBP is a promising target for minimizing diabetes- and stress-induced inflammation and renovascular injury.

Tissue-Resident Lymphocytes in the Kidney

Turner, Jan-Eric — Wed, 01 Nov 2017 06:17:43 GMT-07:00

It has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.

Insights into the Regulation of Collecting Duct Homeostasis by Small Noncoding RNAs

Phua, Yu Leng — Fri, 08 Dec 2017 08:43:45 GMT-08:00

Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function

Guo, Bing — Tue, 07 Nov 2017 08:42:43 GMT-08:00

Podocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF protein colocalizes with podocyte markers in human and mouse kidneys. Compared with littermate controls, mice in which the Srf gene was conditionally inactivated with NPHS2-Cre exhibited early postnatal proteinuria, hypoalbuminemia, and azotemia. Histologic changes in the mutant mice included glomerular capillary dilation and mild glomerulosclerosis, with reduced expression of multiple canonical podocyte markers. We also noted tubular dilation, cell proliferation, and protein casts as well as reactive changes in mesangial cells and interstitial inflammation. Ultrastructure analysis disclosed foot process effacement with loss of slit diaphragms. To ascertain the importance of SRF cofactors in podocyte function, we disabled the myocardin-related transcription factor A and B genes. Although loss of either SRF cofactor alone had no observable effect in the kidney, deficiency of both recapitulated the Srf-null phenotype. These results establish a vital role for SRF and two SRF cofactors in the maintenance of podocyte structure and function.

Any Progress in the Treatment of Antibody-Mediated Rejection?

Budde, Klemens — Thu, 25 Jan 2018 06:04:05 GMT-08:00

TRPC5 Does Not Cause or Aggravate Glomerular Disease

Wang, Xuexiang — Mon, 23 Oct 2017 06:02:12 GMT-07:00

Transient receptor potential channel 5 (TRPC5) is highly expressed in brain and kidney and mediates calcium influx and promotes cell migration. In the kidney, loss of TRPC5 function has been reported to benefit kidney filter dynamics by balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function studies of TRPC5 with respect to kidney function have not been reported. To address this gap, we developed two transgenic mouse models on the C57BL/6 background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant. Compared with nontransgenic controls, neither transgenic model exhibited an increase in proteinuria at 8 months of age or a difference in LPS-induced albuminuria. Moreover, activation of TRPC5 by Englerin A did not stimulate proteinuria, and inhibition of TRPC5 by ML204 did not significantly lower the level of LPS-induced proteinuria in any group. Collectively, these data suggest that the overexpression or activation of the TRPC5 ion channel does not cause kidney barrier injury or aggravate such injury under pathologic conditions.

Banff Classification of Polyomavirus Nephropathy: A New Tool for Research and Clinical Practice

B. Kopp, Jeffrey — Thu, 25 Jan 2018 06:04:05 GMT-08:00

Hyperkalemia across the Continuum of Kidney Function

Palmer, Biff F. — Tue, 07 Nov 2017 08:42:21 GMT-08:00

Outcomes of In–Hospital Cardiopulmonary Resuscitation in Patients with CKD

Saeed, Fahad — Thu, 21 Jul 2016 06:25:38 GMT-07:00

A Concept–Wide Association Study of Clinical Notes to Discover New Predictors of Kidney Failure

Singh, Karandeep — Mon, 10 Oct 2016 04:58:33 GMT-07:00

Progression of Interstitial Fibrosis during the First Year after Deceased Donor Kidney Transplantation among Patients with and without Delayed Graft Function

Heilman, Raymond L. — Mon, 24 Oct 2016 08:02:50 GMT-07:00

Progression of Interstitial Fibrosis in Kidney Transplantation

Oberbauer, Rainer — Mon, 24 Oct 2016 08:02:49 GMT-07:00

Association of Increasing GFR with Change in Albuminuria in the General Population

Melsom, Toralf — Wed, 28 Sep 2016 11:21:28 GMT-07:00

Acute Kidney Injury in the Era of the AKI E-Alert

Holmes, Jennifer — Fri, 28 Oct 2016 05:09:45 GMT-07:00

Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational Research

Clark, Edward — Tue, 07 Jun 2016 07:13:33 GMT-07:00

Concerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation–based mastery learning programs have been shown to be effective in improving fellows’ skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement.

Sex and the Risk of AKI Following Cardio-thoracic Surgery: A Meta-Analysis

Neugarten, Joel — Thu, 20 Oct 2016 06:35:04 GMT-07:00

Conservative Management and End-of-Life Care in an Australian Cohort with ESRD

Morton, Rachael L. — Mon, 03 Oct 2016 08:49:30 GMT-07:00

Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with Paraproteinemias

Motwani, Shveta S. — Mon, 15 Aug 2016 04:05:38 GMT-07:00

Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein–related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.

Vancomycin and the Risk of AKI: A Systematic Review and Meta-Analysis

Sinha Ray, Abhisekh — Mon, 28 Nov 2016 07:51:28 GMT-08:00

Association of Nondisease-Specific Problems with Mortality, Long-Term Care, and Functional Impairment among Older Adults Who Require Skilled Nursing Care after Dialysis Initiation

Bowling, C. Barrett — Wed, 12 Oct 2016 08:52:56 GMT-07:00

The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase–Associated Lipocalin with Progression from CKD to ESRD

Alderson, Helen V. — Wed, 16 Nov 2016 07:18:31 GMT-08:00

Vancomycin and the Risk of AKI: Now Clearer than Mississippi Mud

Nolin, Thomas D. — Mon, 28 Nov 2016 07:51:28 GMT-08:00

Comparative Effectiveness of Second-Line Agents for the Treatment of Diabetes Type 2 in Preventing Kidney Function Decline

Hung, Adriana M. — Tue, 08 Nov 2016 11:03:48 GMT-08:00

Second-Line Agents for the Treatment of Type 2 Diabetes and Prevention of CKD

Yu, Margaret K. — Tue, 08 Nov 2016 11:03:46 GMT-08:00

Prevalence and Contents of Advance Directives of Patients with ESRD Receiving Dialysis

Feely, Molly A. — Thu, 17 Nov 2016 07:19:05 GMT-08:00

Paraprotein–Related Kidney Disease: Attack of the Killer M Proteins

Perazella, Mark A. — Wed, 07 Dec 2016 10:00:36 GMT-08:00

Paraproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics. This Moving Points in Nephrology will provide an update for the Clinical Journal of the American Society of Nephrology readership on some of the clinically relevant kidney lesions associated with monoclonal paraprotein production and the pathophysiology underlying these kidney lesions.

Prognostic Value of Histologic Classification of ANCA-Associated Glomerulonephritis

Bjørneklett, Rune — Tue, 18 Oct 2016 05:20:34 GMT-07:00

Glomerular Pathology in Dent Disease and Its Association with Kidney Function

Wang, Xiangling — Mon, 03 Oct 2016 08:49:29 GMT-07:00

Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy

Finkel, Kevin W. — Mon, 15 Aug 2016 04:05:38 GMT-07:00

Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm–Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high–cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high–cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.

Paraprotein–Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance

Rosner, Mitchell H. — Mon, 15 Aug 2016 04:05:37 GMT-07:00

Paraprotein–related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.

Paraprotein–Related Kidney Disease: Kidney Injury from Paraproteins—What Determines the Site of Injury?

Doshi, Mona — Mon, 15 Aug 2016 04:05:38 GMT-07:00

Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light–chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.

Working Toward More Effective Advance Care Planning in Patients with ESRD

Combs, Sara Ann — Thu, 17 Nov 2016 07:19:05 GMT-08:00

Inhibition of Activin Signaling Slows Progression of Polycystic Kidney Disease

Leonhard, Wouter N. — Mon, 28 Mar 2016 06:04:43 GMT-07:00

Autosomal dominant polycystic kidney disease (ADPKD), characterized by the formation of numerous kidney cysts, is caused by PKD1 or PKD2 mutations and affects 0.1% of the population. Although recent clinical studies indicate that reduction of cAMP levels slows progression of PKD, this finding has not led to an established safe and effective therapy for patients, indicating the need to find new therapeutic targets. The role of TGF-β in PKD is not clearly understood, but nuclear accumulation of phosphorylated SMAD2/3 in cyst-lining cells suggests the involvement of TGF-β signaling in this disease. In this study, we ablated the TGF-β type 1 receptor (also termed activin receptor–like kinase 5) in renal epithelial cells of PKD mice, which had little to no effect on the expression of SMAD2/3 target genes or the progression of PKD. Therefore, we investigated whether alternative TGF-β superfamily ligands account for SMAD2/3 activation in cystic epithelial cells. Activins are members of the TGF-β superfamily and drive SMAD2/3 phosphorylation via activin receptors, but activins have not been studied in the context of PKD. Mice with PKD had increased expression of activin ligands, even at early stages of disease. In addition, treatment with a soluble activin receptor IIB fusion (sActRIIB-Fc) protein, which acts as a soluble trap to sequester activin ligands, effectively inhibited cyst formation in three distinct mouse models of PKD. These data point to activin signaling as a key pathway in PKD and a promising target for therapy.

A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial Nephritis

Airik, Rannar — Tue, 29 Mar 2016 07:00:05 GMT-07:00

Karyomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia–related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1 knockout mouse model, with abrogation of Fan1 expression confirmed by quantitative RT-PCR. Challenging Fan1−/− and wild-type mice with 20 mg/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1−/− mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of Fan1−/− mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that FAN1 mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover, Fan1−/− mice provide a new model with which to study the pathomechanisms of CKD.

Capillary Rarefaction Associates with Albuminuria: The Maastricht Study

Martens, Remy J.H. — Mon, 09 May 2016 06:33:56 GMT-07:00

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.

Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the Glomerular Glycocalyx

Garsen, Marjolein — Tue, 29 Mar 2016 07:00:04 GMT-07:00

Diabetic nephropathy (DN) is the leading cause of CKD in the Western world. Endothelin receptor antagonists have emerged as a novel treatment for DN, but the mechanisms underlying the protective effect remain unknown. We previously showed that both heparanase and endothelin-1 are essential for the development of DN. Here, we further investigated the role of these proteins in DN, and demonstrated that endothelin-1 activates podocytes to release heparanase. Furthermore, conditioned podocyte culture medium increased glomerular transendothelial albumin passage in a heparanase-dependent manner. In mice, podocyte-specific knockout of the endothelin receptor prevented the diabetes-induced increase in glomerular heparanase expression, consequent reduction in heparan sulfate expression and endothelial glycocalyx thickness, and development of proteinuria observed in wild-type counterparts. Our data suggest that in diabetes, endothelin-1 signaling, as occurs in endothelial activation, induces heparanase expression in the podocyte, damage to the glycocalyx, proteinuria, and renal failure. Thus, prevention of these effects may constitute the mechanism of action of endothelin receptor blockers in DN.

Coronary Revascularization in Patients with CKD Stage 5D: Pragmatic Considerations

Shroff, Gautam R. — Thu, 04 Aug 2016 05:44:09 GMT-07:00

Coronary revascularization decisions for patients with CKD stage 5D present a dilemma for clinicians because of high baseline risks of mortality and future cardiovascular events. This population differs from the general population regarding characteristics of coronary plaque composition and behavior, accuracy of noninvasive testing, and response to surgical and percutaneous revascularization, such that findings from the general population cannot be automatically extrapolated. However, this high-risk population has been excluded from all randomized trials evaluating outcomes of revascularization. Observational studies have attempted to address long-term outcomes after surgical versus percutaneous revascularization strategies, but inherent selection bias may limit accuracy. Compared with percutaneous strategies, surgical revascularization seems to have long–term survival benefit on the basis of observational data but associates with substantially higher short–term mortality rates. Percutaneous revascularization with drug-eluting and bare metal stents associates with a high risk of in-stent restenosis and need for future revascularization, perhaps contributing to the higher long–term mortality hazard. Off–pump coronary bypass surgery and the newest generation of drug–eluting stent platforms offer no definitive benefits. In this review, we address the nuances, complexities, and tradeoffs that clinicians face in determining the optimal method of coronary revascularization for this high-risk population.

Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

Alexander, R. Todd — Thu, 28 Jul 2016 05:44:08 GMT-07:00

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.

Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula Development

Allon, Michael — Mon, 09 May 2016 06:33:55 GMT-07:00

Arteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; P<0.01; change in diameter =0.45 mm; 95% CI, 0.25 to 0.65 mm; P<0.001). Greater FMD also associated with greater increases in 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in FMD: change in blood flow rate =11.6%; 95% CI, 0.6% to 23.9%; P=0.04; change in diameter =0.31 mm; 95% CI, 0.05 to 0.57 mm; P=0.02). None of the remaining VFT parameters exhibited consistent statistically significant relationships with both postoperative AVF blood flow rate and diameter. In conclusion, preoperative NMD and FMD positively associated with changes in 6-week AVF blood flow rate and diameter, suggesting that native functional arterial properties affect AVF development.

This Month's Highlights

American Society of Nephrology — Wed, 30 Nov 2016 10:00:46 GMT-08:00

Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic Context

Leonhard, Wouter N. — Thu, 04 Aug 2016 05:44:10 GMT-07:00

Patients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys. However, the large intrafamilial variation in the progression rate of ADPKD suggests involvement of additional factors other than the type of mutation. The identification of these factors will increase our understanding of ADPKD and could ultimately help in the development of a clinically relevant therapy. Our review addresses the mechanisms by which various biologic processes influence cyst formation and cyst growth, thereby explaining an important part of the inter- and intrafamilial variability in ADPKD. Numerous studies from many laboratories provide compelling evidence for the influence on cyst formation by spatiotemporal gene inactivation, the genetic context, the metabolic status, the presence of existing cysts, and whether the kidneys were challenged by renal injury. Collectively, a solid basis is provided for the concept that the probability of cyst formation is determined by functional PKD protein levels and the biologic context. We model these findings in a graphic representation called the cystic probability landscape, providing a robust conceptual understanding of why cells sometimes do or do not form cysts.

Phospholipase A2 Receptor–Related Membranous Nephropathy and Mannan-Binding Lectin Deficiency

Bally, Stéphane — Fri, 06 May 2016 08:56:02 GMT-07:00

Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at −550 (L/L) and −221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.

Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin Lineage

Lichtnekert, Julia — Thu, 14 Apr 2016 08:01:57 GMT-07:00

Because adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP+CoRL and, within these glomeruli, more RFP+CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP+CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells (α8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.

Low–Energy Shockwave Therapy Improves Ischemic Kidney Microcirculation

Zhang, Xin — Mon, 13 Jun 2016 11:37:23 GMT-07:00

Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low–energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low–energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low–energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo. A 3-week low–energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low–energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low–energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.

Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule Development

Akchurin, Oleh — Mon, 16 May 2016 08:22:22 GMT-07:00

The kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore, we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.

Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients

Obi, Yoshitsugu — Wed, 11 May 2016 05:46:37 GMT-07:00

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9–5.0) and −1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of −6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix–adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: −1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.

Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis

Kurella Tamura, Manjula — Thu, 21 Jul 2016 06:40:51 GMT-07:00

Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites—4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline—were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis

Liappas, Georgios — Thu, 05 May 2016 07:03:10 GMT-07:00

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.

Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China

Xu, Xin — Thu, 30 Jun 2016 07:40:48 GMT-07:00

The effect of air pollution on the changing pattern of glomerulopathy has not been studied. We estimated the profile of and temporal change in glomerular diseases in an 11-year renal biopsy series including 71,151 native biopsies at 938 hospitals spanning 282 cities in China from 2004 to 2014, and examined the association of long-term exposure to fine particulate matter of <2.5 μm (PM2.5) with glomerulopathy. After age and region standardization, we identified IgA nephropathy as the leading type of glomerulopathy, with a frequency of 28.1%, followed by membranous nephropathy (MN), with a frequency of 23.4%. Notably, the adjusted odds for MN increased 13% annually over the 11-year study period, whereas the proportions of other major glomerulopathies remained stable. During the study period, 3-year average PM2.5 exposure varied among the 282 cities, ranging from 6 to 114 μg/m3 (mean, 52.6 μg/m3). Each 10 μg/m3 increase in PM2.5 concentration associated with 14% higher odds for MN (odds ratio, 1.14; 95% confidence interval, 1.10 to 1.18) in regions with PM2.5 concentration >70 μg/m3. We also found that higher 3-year average air quality index was associated with increased risk of MN. In conclusion, in this large renal biopsy series, the frequency of MN increased over the study period, and long-term exposure to high levels of PM2.5 was associated with an increased risk of MN.

Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft Rejection

Ville, Simon — Mon, 09 May 2016 06:33:57 GMT-07:00

Belatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab′ antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid–resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell–specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preexisting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

Bruggeman, Leslie A. — Tue, 29 Mar 2016 07:00:06 GMT-07:00

APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.

Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts

Li, Yuanyuan — Fri, 06 May 2016 08:56:00 GMT-07:00

The gene for ADP ribosylation factor–like GTPase 13B (Arl13b) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts. To investigate whether Arl13b has a role in ciliogenesis in mammalian kidney and whether loss of function of Arl13b leads to cystic kidneys in mammals, we generated a mouse model with kidney–specific conditional knockout of Arl13b. Deletion of Arl13b in the distal nephron at the perinatal stage led to a cilia biogenesis defect and rapid kidney cyst formation. Additionally, we detected misregulation of multiple pathways in the cystic kidneys of this model. Moreover, valproic acid, a histone deacetylase inhibitor that we previously showed slows cyst progression in a mouse cystic kidney model with neonatal inactivation of Pkd1, inhibited the early rise of Wnt7a expression, ameliorated fibrosis, slowed cyst progression, and improved kidney function in the Arl13b mutant mouse. Finally, in rescue experiments in zebrafish, all ARL13B allele combinations identified in patients with Joubert syndrome provided residual Arl13b function, supporting the idea that the lack of cystic kidney phenotype in human patients with ARL13B mutations is explained by the hypomorphic nature of the mutations.

TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic Kidney Disease

Gomez, Ivan G. — Tue, 29 Mar 2016 07:00:03 GMT-07:00

The identification of the cellular origins of myofibroblasts has led to the discovery of novel pathways that potentially drive myofibroblast perpetuation in disease. Here, we further investigated the role of innate immune signaling pathways in this process. In mice, renal injury-induced activation of pericytes, which are myofibroblast precursors attached to endothelial cells, led to upregulated expression of TNF receptor superfamily member 12a, also known as fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte detachment from capillaries. In vitro, administration of TWEAK activated and differentiated pericytes into cytokine-producing myofibroblasts, and further activated established myofibroblasts in a manner requiring canonical and noncanonical NF-κB signaling pathways. Deficiency of Fn14 protected mouse kidneys from fibrogenesis, inflammation, and associated vascular instability after in vivo injury, and was associated with loss of NF-κB signaling. In a genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking antibodies attenuated disease progression, preserved organ function, and increased survival. These results identify the TWEAK-Fn14 signaling pathway as an important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease progression.

Role of Ragulator in the Regulation of Mechanistic Target of Rapamycin Signaling in Podocytes and Glomerular Function

Yao, Yao — Thu, 31 Mar 2016 07:21:59 GMT-07:00

Aberrant activation of mechanistic target of rapamycin complex 1 (mTORC1) in glomerular podocytes leads to glomerular insufficiency and may contribute to the development of glomerular diseases, including diabetic nephropathy. Thus, an approach for preventing mTORC1 activation may allow circumvention of the onset and progression of mTORC1-dependent podocyte injury and glomerular diseases. mTORC1 activation requires inputs from both growth factors and nutrients that inactivate the tuberous sclerosis complex (TSC), a key suppressor of mTORC1, on the lysosome. Previous studies in mice revealed that the growth factor-phosphatidylinositol 3-kinase pathway and mTORC1 are essential for maintaining normal podocyte function, suggesting that direct inhibition of the phosphatidylinositol 3-kinase pathway or mTORC1 may not be an ideal approach to sustaining physiologic podocyte functions under certain disease conditions. Here, we report the role of the Ragulator complex, which recruits mTORC1 to lysosomes in response to nutrient availability in podocytes. Notably, podocytes lacking Ragulator maintain basal mTORC1 activity. Unlike podocyte-specific mTORC1-knockout mice, mice lacking functional Ragulator in podocytes did not show abnormalities in podocyte or glomerular function. However, aberrant mTORC1 activation induced by active Rheb in podocyte-specific TSC1-knockout (podo-TSC1 KO) mice did require Ragulator. Moreover, ablation of Ragulator in the podocytes of podo-TSC1 KO mice or streptozotocin-induced diabetic mice significantly blocked the development of pathologic renal phenotypes. These observations suggest that the blockade of mTORC1 recruitment to lysosomes may be a useful clinical approach to attenuate aberrant mTORC1 activation under certain disease conditions.

IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases

Riedel, Jan-Hendrik — Wed, 30 Mar 2016 06:21:53 GMT-07:00

The TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene–deficient mice, IL-17F–neutralizing antibodies, and adoptive transfer experiments into Rag1−/− mice demonstrated that CD4+ T cell–derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F–deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F–deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F–deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti–IL-17 cytokine therapies in TH17-mediated human autoimmune diseases.

Stat3 Controls Tubulointerstitial Communication during CKD

Bienaimé, Frank — Fri, 06 May 2016 08:56:03 GMT-07:00

In CKD, tubular cells may be involved in the induction of interstitial fibrosis, which in turn, leads to loss of renal function. However, the molecular mechanisms that link tubular cells to the interstitial compartment are not clear. Activation of the Stat3 transcription factor has been reported in tubular cells after renal damage, and Stat3 has been implicated in CKD progression. Here, we combined an experimental model of nephron reduction in mice from different genetic backgrounds and genetically modified animals with in silico and in vitro experiments to determine whether the selective activation of Stat3 in tubular cells is involved in the development of interstitial fibrosis. Nephron reduction caused Stat3 phosphorylation in tubular cells of lesion-prone mice but not in resistant mice. Furthermore, specific deletion of Stat3 in tubular cells significantly reduced the extent of interstitial fibrosis, which correlated with reduced fibroblast proliferation and matrix synthesis, after nephron reduction. Mechanistically, in vitro tubular Stat3 activation triggered the expression of a specific subset of paracrine profibrotic factors, including Lcn2, Pdgfb, and Timp1. Together, our results provide a molecular link between tubular and interstitial cells during CKD progression and identify Stat3 as a central regulator of this link and a promising therapeutic target.

Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of Furosemide

Cil, Onur — Fri, 06 May 2016 08:55:59 GMT-07:00

Pendrin is a Cl−/HCO3− exchanger expressed in type B and non-A, non-B intercalated cells in the distal nephron, where it facilitates Cl− absorption and is involved in Na+ absorption and acid-base balance. Pendrin-knockout mice show no fluid-electrolyte abnormalities under baseline conditions, although mice with double knockout of pendrin and the Na+/Cl− cotransporter (NCC) manifest profound salt wasting. Thus, pendrin may attenuate diuretic-induced salt loss, but this function remains unconfirmed. To clarify the physiologic role of pendrin under conditions not confounded by gene knockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput screen. In vitro, a pyrazole-thiophenesulfonamide, PDSinh-C01, inhibited Cl−/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1–3 µM, without affecting other major kidney tubule transporters. Administration of PDSinh-C01 to mice at predicted therapeutic doses, determined from serum and urine pharmacokinetics, did not affect urine output, osmolality, salt excretion, or acid-base balance. However, in mice treated acutely with furosemide, administration of PDSinh-C01 produced a 30% increase in urine output, with increased Na+ and Cl− excretion. In mice treated long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increase in urine output. Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the action of loop diuretics. Such combination therapy might enhance diuresis and salt excretion for treatment of hypertension and edema, perhaps including diuretic-resistant edema.

Predicting the Functionality and Form of a Dialysis Fistula

Nath, Karl A. — Thu, 04 Aug 2016 05:44:08 GMT-07:00

Beyond EMT: Epithelial STAT3 as a Central Regulator of Fibrogenesis

Duffield, Jeremy S. — Fri, 01 Jul 2016 05:43:27 GMT-07:00

Pendrin—A New Target for Diuretic Therapy?

Wagner, Carsten A. — Thu, 11 Aug 2016 08:00:57 GMT-07:00

Preserving Residual Kidney Function in Hemodialysis Patients—Back in the Spotlight

Wang, Angela Yee-Moon — Thu, 04 Aug 2016 05:44:09 GMT-07:00

Neither Hematocrit Normalization nor Exercise Training Restores Oxygen Consumption to Normal Levels in Hemodialysis Patients

Stray-Gundersen, James — Fri, 06 May 2016 08:56:03 GMT-07:00

Patients treated with hemodialysis develop severely reduced functional capacity, which can be partially ameliorated by correcting anemia and through exercise training. In this study, we determined perturbations of an erythroid-stimulating agent and exercise training to examine if and where limitation to oxygen transport exists in patients on hemodialysis. Twenty-seven patients on hemodialysis completed a crossover study consisting of two exercise training phases at two hematocrit (Hct) values: 30% (anemic) and 42% (physiologic; normalized by treatment with erythroid-stimulating agent). To determine primary outcome measures of peak power and oxygen consumption (VO2) and secondary measures related to components of oxygen transport and utilization, all patients underwent numerous tests at five time points: baseline, untrained at Hct of 30%, after training at Hct of 30%, untrained at Hct of 42%, and after training at Hct of 42%. Hct normalization, exercise training, or the combination thereof significantly improved peak power and VO2 relative to values in the untrained anemic phase. Hct normalization increased peak arterial oxygen and arteriovenous oxygen difference, whereas exercise training improved cardiac output, citrate synthase activity, and peak tissue diffusing capacity. However, although the increase in arterial oxygen observed in the combination phase reached a value similar to that in healthy sedentary controls, the increase in peak arteriovenous oxygen difference did not. Muscle biopsy specimens showed markedly thickened endothelium and electron–dense interstitial deposits. In conclusion, exercise and Hct normalization had positive effects but failed to normalize exercise capacity in patients on hemodialysis. This effect may be caused by abnormalities identified within skeletal muscle.

Cold Shock Proteins Mediate GN with Mesangioproliferation

Zhu, Cheng — Thu, 05 May 2016 07:03:12 GMT-07:00

DNA binding protein A (DbpA) is a member of the human cold shock domain–containing protein superfamily, with known functions in cell proliferation, differentiation, and stress responses. DbpA mediates tight junction–associated activities in tubular epithelial cells, but the function of DbpA in mesangial cells is unknown. Here, we found DbpA protein expression restricted to vascular smooth muscle cells in healthy human kidney tissue but profound induction of DbpA protein expression within the glomerular mesangial compartment in mesangioproliferative nephritis. In vitro, depletion or overexpression of DbpA using lentiviral constructs led to inhibition or promotion, respectively, of mesangial cell proliferation. Because platelet–derived growth factor B (PDGF-B) signaling has a pivotal role in mesangial cell proliferation, we examined the regulatory effect of PDGF-B on DbpA. In vitro studies of human and rat mesangial cells confirmed a stimulatory effect of PDGF-B on DbpA transcript numbers and protein levels. Additional in vivo investigations showed DbpA upregulation in experimental rat anti–Thy1.1 nephritis and murine mesangioproliferative nephritis models. To interfere with PDGF-B signaling, we injected nephritic rats with PDGF-B neutralizing aptamers or the MEK/ERK inhibitor U0126. Both interventions markedly decreased DbpA protein expression. Conversely, continuous PDGF-B infusion in healthy rats induced DbpA expression predominantly within the mesangial compartment. Taken together, these results indicate that DbpA is a novel target of PDGF-B signaling and a key mediator of mesangial cell proliferation.

Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney Disease

Salih, Mahdi — Thu, 03 Mar 2016 10:59:04 GMT-08:00

Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs from healthy controls and patients with ADPKD using a labeled approach and then used a label-free approach with uEVs of different subjects (healthy controls versus patients with ADPKD versus patients with non-ADPKD CKD). In both experiments, 30 proteins were consistently more abundant (by two-fold or greater) in ADPKD-uEVs than in healthy- and CKD-uEVs. Of these proteins, we selected periplakin, envoplakin, villin-1, and complement C3 and C9 for confirmation because they were also significantly overrepresented in pathway analysis and were previously implicated in ADPKD pathogenesis. Immunoblotting confirmed higher abundances of the selected proteins in uEVs from three independent groups of patients with ADPKD. Whereas uEVs of young patients with ADPKD and preserved kidney function already had higher levels of complement, only uEVs of patients with advanced stages of ADPKD had increased levels of villin-1, periplakin, and envoplakin. Furthermore, all five proteins correlated positively with total kidney volume. Analysis in kidney tissue from mice with kidney-specific, tamoxifen-inducible Pkd1 deletion demonstrated higher expression in more severe stages of the disease and correlation with kidney weight for each protein of interest. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.

Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based Cohort

Kozlitina, Julia — Tue, 22 Mar 2016 05:24:27 GMT-07:00

Two common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1‑HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1‑HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1‑HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1-dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1‑HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein (HPR), APOL1, and ubiquitin D (UBD) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein.

Gene Editing: Powerful New Tools for Nephrology Research and Therapy

Miyagi, Ayano — Wed, 29 Jun 2016 06:49:36 GMT-07:00

Biologic research is experiencing a transformation brought about by the ability of programmable nucleases to manipulate the genome. In the recently developed CRISPR/Cas system, short RNA sequences guide the endonuclease Cas9 to any location in the genome, causing a DNA double–strand break (DSB). Repair of DSBs allows the introduction of targeted genetic manipulations with high precision. Cas9–mediated gene editing is simple, scalable, and rapid, and it can be applied to virtually any organism. Here, we summarize the development of modern gene editing techniques and the biology of DSB repair on which these techniques are based. We discuss technical points in applying this technology and review its use in model organisms. Finally, we describe prospects for the use of gene editing to treat human genetic diseases. This technology offers tremendous promise for equipping the nephrology research community to better model and ultimately, treat kidney diseases.

The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution

Ghirotto, Silvia — Thu, 10 Mar 2016 07:57:46 GMT-08:00

Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.

Sex Differences in Renal Proximal Tubular Cell Homeostasis

Seppi, Thomas — Thu, 28 Apr 2016 06:19:55 GMT-07:00

Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase–α. Additionally, we quantified urinary excretion of blood plasma proteins α1–microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase–α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1–microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ–derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

This Month's Highlights

American Society of Nephrology — Fri, 30 Sep 2016 10:00:56 GMT-07:00

Developmental Origins for Kidney Disease Due to Shroom3 Deficiency

Khalili, Hadiseh — Thu, 03 Mar 2016 10:59:08 GMT-08:00

CKD is a significant health concern with an underlying genetic component. Multiple genome–wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman’s capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho–kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.

Autoantibodies Targeting a Collecting Duct–Specific Water Channel in Tubulointerstitial Nephritis

Landegren, Nils — Wed, 16 Mar 2016 10:09:03 GMT-07:00

Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct–specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.

Mesencephalic Astrocyte–Derived Neurotrophic Factor as a Urine Biomarker for Endoplasmic Reticulum Stress–Related Kidney Diseases

Kim, Yeawon — Thu, 03 Mar 2016 10:58:57 GMT-08:00

Endoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte–derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β2 protein–induced podocyte ER stress and AKI triggered by tunicamycin– or ischemia-reperfusion–induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress–related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.

Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health Initiative

Dember, Laura M. — Mon, 11 Jul 2016 03:56:24 GMT-07:00

Pragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues.

Current and Emerging Therapies for Lupus Nephritis

Parikh, Samir V. — Thu, 09 Jun 2016 07:35:15 GMT-07:00

The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.

EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water Reabsorption

Cheung, Pui W. — Wed, 09 Mar 2016 09:59:04 GMT-08:00

Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high–throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal cells and reduced urine volume by 45% after 5 days of treatment in mice with lithium-induced NDI. Similar to VP, erlotinib increased exocytosis and decreased endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2 membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner. However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and protein kinase A. Conversely, EGF reduced VP–induced AQP2 Ser-256 phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and a role of EGF in water homeostasis. These results reveal a novel pathway that contributes to the regulation of AQP2–mediated water reabsorption and suggest new potential therapeutic strategies for NDI treatment.

Pragmatic Clinical Trials in CKD: Opportunities and Challenges

de Boer, Ian H. — Thu, 09 Jun 2016 07:35:20 GMT-07:00

Randomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.

Trabecular Bone Score and Incident Fragility Fracture Risk in Adults with Reduced Kidney Function

Naylor, Kyla L. — Mon, 24 Oct 2016 08:02:49 GMT-07:00

Use of Electronic Health Data to Estimate Heart Failure Events in a Population-Based Cohort with CKD

Floyd, James S. — Tue, 09 Aug 2016 05:44:44 GMT-07:00

Cardiovascular Disease Risk Factors and Left Ventricular Hypertrophy in Girls and Boys With CKD

Ruebner, Rebecca L. — Wed, 14 Sep 2016 07:17:54 GMT-07:00

Recurrent FSGS Postkidney Transplant: Moving the Needle Forward

Amaral, Sandra — Thu, 20 Oct 2016 06:35:04 GMT-07:00

Long-Term Outcome of Kidney Transplantation in Recipients with Focal Segmental Glomerulosclerosis

Francis, Anna — Thu, 20 Oct 2016 06:35:05 GMT-07:00

Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting List

Wainright, Jennifer L. — Fri, 02 Sep 2016 04:14:18 GMT-07:00

Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Portale, Anthony A. — Thu, 25 Aug 2016 05:48:41 GMT-07:00

NT-proBNP and Echocardiographic Parameters for Prediction of Cardiovascular Outcomes in Patients with CKD Stages G2–G4

Untersteller, Kathrin — Thu, 11 Aug 2016 08:21:50 GMT-07:00

Development of a Multicenter Ward–Based AKI Prediction Model

Koyner, Jay L. — Thu, 15 Sep 2016 06:02:45 GMT-07:00

Incidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System Blockade

Palevsky, Paul M. — Tue, 27 Sep 2016 07:05:57 GMT-07:00

Defining Glomerular Disease in Mechanistic Terms: Implementing an Integrative Biology Approach in Nephrology

Mariani, Laura H. — Wed, 14 Sep 2016 07:17:53 GMT-07:00

Advances in biomedical research allow for the capture of an unprecedented level of genetic, molecular, and clinical information from large patient cohorts, where the quest for precision medicine can be pursued. An overarching goal of precision medicine is to integrate the large–scale genetic and molecular data with deep phenotypic information to identify a new mechanistic disease classification. This classification can ideally be used to meet the clinical goal of the right medication for the right patient at the right time. Glomerular disease presents a formidable challenge for precision medicine. Patients present with similar signs and symptoms, which cross the current disease categories. The diseases are grouped by shared histopathologic features, but individual patients have dramatic variability in presentation, progression, and response to therapy, reflecting the underlying biologic heterogeneity within each glomerular disease category. Despite the clinical challenge, glomerular disease has several unique advantages to building multilayered datasets connecting genetic, molecular, and structural information needed to address the goals of precision medicine in this population. Kidney biopsy tissue, obtained during routine clinical care, provides a direct window into the molecular mechanisms active in the affected organ. In addition, urine is a biofluid ideally suited for repeated measurement from the diseased organ as a liquid biopsy with potential to reflect the dynamic state of renal tissue. In our review, current approaches for large–scale data generation and integration along the genotype-phenotype continuum in glomerular disease will be summarized. Several successful examples of this integrative biology approach within glomerular disease will be highlighted along with an outlook on how achieving a mechanistic disease classification could help to shape glomerular disease research and care in the future.

Introducing the Evidence-Based Nephrology Series

Kestenbaum, Bryan — Mon, 07 Nov 2016 10:00:33 GMT-08:00

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Introduction

Palevsky, Paul M. — Mon, 07 Nov 2016 10:00:33 GMT-08:00

Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care Setting

Tam-Tham, Helen — Mon, 22 Aug 2016 05:32:57 GMT-07:00

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 2

Herzog, Charles A. — Tue, 25 Oct 2016 04:28:27 GMT-07:00

Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study

de Boer, Ian H. — Mon, 24 Oct 2016 08:02:52 GMT-07:00

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 3

Rigatto, Claudio — Tue, 25 Oct 2016 04:28:27 GMT-07:00

Association of Peritonitis with Hemodialysis Catheter Dependence after Modality Switch

Lee, Timmy — Tue, 30 Aug 2016 06:16:50 GMT-07:00

Crackles and Comets: Lung Ultrasound to Detect Pulmonary Congestion in Patients on Dialysis is Coming of Age

Sherman, Richard A. — Thu, 22 Sep 2016 06:35:07 GMT-07:00

Are Ambulatory Care–Sensitive Conditions the Fulcrum of Hospitalizations for CKD Patients?

Fink, Jeffrey C. — Thu, 06 Oct 2016 07:01:30 GMT-07:00

Pharmacotherapy of Hypertension in Chronic Dialysis Patients

Georgianos, Panagiotis I. — Mon, 24 Oct 2016 08:02:52 GMT-07:00

Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.

Commentary on Pharmacotherapy of Hypertension in Patients on Chronic Dialysis

Seliger, Stephen L. — Mon, 24 Oct 2016 08:02:51 GMT-07:00

Correction

American Society of Nephrology — Fri, 21 Oct 2016 08:25:28 GMT-07:00

Potentially Preventable Hospitalization among Patients with CKD and High Inpatient Use

Ronksley, Paul E. — Thu, 06 Oct 2016 07:01:31 GMT-07:00

Use of Oral Anticoagulation for Patients with ESRD on Hemodialysis with Atrial Fibrillation: Verdict 1

Bansal, Nisha — Tue, 25 Oct 2016 04:28:28 GMT-07:00

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study

Torino, Claudia — Thu, 22 Sep 2016 06:35:08 GMT-07:00

Is Change in Albuminuria a Surrogate Marker for Cardiovascular and Renal Outcomes in Type 1 Diabetes?

Dixon, Bradley S. — Mon, 24 Oct 2016 08:02:51 GMT-07:00

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Con

Keskar, Vaibhav — Tue, 25 Oct 2016 04:28:28 GMT-07:00

Among patients with atrial fibrillation, prophylaxis for stroke prevention with the use of anticoagulation is well established in the general population. A number of randomized controlled trials and evidence-based risk prediction tools clearly delineate the benefit and risks of therapy. Despite the high incidence of atrial fibrillation in the late stage CKD and ESRD populations, little high quality evidence exists in these populations. Is it appropriate then to extrapolate findings from the general population to those with CKD/ESRD? In our view, too much uncertainty exists regarding proof of efficacy with clear signals of harm. Routine anticoagulation for stroke prevention in atrial fibrillation is not recommended for the majority of CKD and ESRD patients.

Fractures in Patients with CKD: Time for Action

Moe, Sharon M. — Mon, 24 Oct 2016 08:02:51 GMT-07:00

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Pro

McCullough, Peter A. — Tue, 25 Oct 2016 04:28:28 GMT-07:00

Warfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.

Genetic African Ancestry and Markers of Mineral Metabolism in CKD

Gutiérrez, Orlando M. — Mon, 08 Feb 2016 06:50:45 GMT-08:00

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

Cha, Ran-hui — Tue, 09 Feb 2016 08:37:43 GMT-08:00

Association of Performance-Based and Self–Reported Function–Based Definitions of Frailty with Mortality among Patients Receiving Hemodialysis

Johansen, Kirsten L. — Wed, 20 Jan 2016 07:24:35 GMT-08:00

Peripheral Edema, Central Venous Pressure, and Risk of AKI in Critical Illness

Chen, Kenneth P. — Tue, 19 Jan 2016 06:59:06 GMT-08:00

External Validation of the Kidney Failure Risk Equation and Re-Calibration with Addition of Ultrasound Parameters

Lennartz, Claudia S. — Tue, 19 Jan 2016 06:59:07 GMT-08:00

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

Meyring-Wösten, Anna — Wed, 02 Mar 2016 06:43:30 GMT-08:00

Approach to the Highly Sensitized Kidney Transplant Candidate

Keith, Douglas S. — Thu, 25 Feb 2016 07:14:57 GMT-08:00

For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.

Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children

Ravani, Pietro — Thu, 19 Nov 2015 06:12:14 GMT-08:00

Rituximab, a chimeric anti-CD20 monoclonal antibody originally licensed for lymphoma, is emerging as a novel steroid-sparing agent for idiopathic nephrotic syndrome in children. The potential use of anti-CD20 monoclonal antibodies in idiopathic nephrotic syndrome has contributed to shifting the view of podocytopathies from T cell–mediated to more complex immunomediated disorders that can benefit from targeting B cells and other mediators of the early immune response. Clinical data on the use of rituximab also have implications on disease management and classification. In this review, we present results of clinical studies that support rituximab as an effective steroid-sparing agent in steroid-dependent idiopathic nephrotic syndrome. Recent randomized controlled trials suggest that potential benefits of rituximab therapy in steroid-dependent forms of idiopathic nephrotic syndrome vary depending on whether children are dependent on steroids alone or on both steroids and calcineurin inhibitors, with greater probabilities to achieve drug-free remission in the former group. Multiple-drug dependence may identify a different disease state with different prognosis and treatment options. Insufficient data are available on optimal use of rituximab as a maintenance steroid-sparing agent in these steroid-sensitive forms of the disease, including how often and for how long rituximab infusions should be repeated to maximize expected benefits and minimize potential harms. Finally, one randomized controlled trial in children with steroid-resistant idiopathic nephrotic syndrome yielded negative results. New anti-CD20 antibodies are under study in this patient population.

Lupus Podocytopathy: A Distinct Entity

Bomback, Andrew S. — Wed, 16 Mar 2016 10:16:15 GMT-07:00

Emergency Department Visits after Kidney Transplantation

Schold, Jesse D. — Thu, 24 Mar 2016 06:41:23 GMT-07:00

Emergency Department Visits after Kidney Transplantation

Dalrymple, Lorien S. — Thu, 24 Mar 2016 06:41:23 GMT-07:00

American Society of Nephrology Quiz and Questionnaire 2015: Electrolytes and Acid–Base Disorders

Rosner, Mitchell H. — Fri, 29 Jan 2016 06:46:12 GMT-08:00

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. During the 2015 meeting the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid–base disorders, glomerular disease, end-stage renal disease and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single-best-answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cell-phone app containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.

Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System

Trepiccione, Francesco — Mon, 04 Apr 2016 07:51:20 GMT-07:00

ATPase H+-transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H+-ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na+-K+-2Cl− cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity.

Relationship between eGFR Decline and Hard Outcomes after Kidney Transplants

Clayton, Philip A. — Fri, 08 Apr 2016 05:34:15 GMT-07:00

Trials designed to assess the effect of interventions on death and graft failure in kidney transplant recipients are not feasible, because these are predominantly late events. Here, we examined the potential of percentage decline in eGFR as a surrogate for hard outcomes. We obtained deidentified data from the Australia and New Zealand Dialysis and Transplant Registry and studied 7949 transplants performed from 1995 to 2009, including 71,845 patient-years of follow-up, 1121 graft losses, and 1192 deaths. We used adjusted Cox proportional hazards models to determine risks of death or death–censored graft failure related to percentage change in eGFR between years 1 and 3 after transplant. Percentage change in eGFR was modeled as a restricted cubic spline. Rate of eGFR decline associated with exponentially increased risks of graft failure and death. Compared with stable eGFR, a ≥30% decline in eGFR, detected in 10% of patients, strongly associated with subsequent death (hazard ratio, 2.20; 95% confidence interval, 1.87 to 2.60) and death–censored graft failure (hazard ratio, 5.14; 95% confidence interval, 4.44 to 5.95). Decline in eGFR was superior to other surrogates, including acute rejection, doubling of serum creatinine level, and eGFR at year 1 or year 2. We conclude that 30% decline in eGFR between years 1 and 3 after kidney transplant is common and strongly associated with risks of subsequent death and death–censored graft failure, which mirrors findings in CKD. Percentage decline in eGFR should be considered for use as a surrogate outcome in kidney transplant trials.

Bad Memory: CD4 T Cell Presensitization Fosters Antibody-Mediated Kidney Transplant Rejection

Dean, Patrick G. — Wed, 25 May 2016 06:24:09 GMT-07:00

Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis

Tereshchenko, Larisa G. — Fri, 29 Apr 2016 06:40:10 GMT-07:00

The single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78–151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m2.7. During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal–averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal–averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.

Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics

Brähler, Sebastian — Fri, 01 Apr 2016 07:44:02 GMT-07:00

In glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro. However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two–photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1, however, podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Constitutive activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we detected detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. Podocyte membrane activity also increased in the inflammatory environment of immune complex–mediated GN. Our results provide evidence that podocytes transition from a static to a dynamic state in vivo, shedding new light on mechanisms in foot process effacement.

The Current State of Peritoneal Dialysis

Mehrotra, Rajnish — Thu, 23 Jun 2016 07:48:49 GMT-07:00

Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.

Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria

Korstanje, Ron — Mon, 28 Mar 2016 06:04:46 GMT-07:00

Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes.

2015 Homer W. Smith Award: The Podocyte from Periphery to Center Stage

Kerjaschki, Dontscho — Mon, 20 Jun 2016 06:00:04 GMT-07:00

This overview summarizes selected major developments over the last 40 years in understanding podocyte biology and its involvement in glomerular disease subjectively from my perspective. Serendipity has played a major role in my contributions to investigative nephrology that range from basic mechanisms of immune deposit formation in experimental membranous nephropathy to the role of a microRNA in FSGS. This review emphasizes the importance of continuous reality checks of experimental results obtained in vitro or with genetically modified animals with human disease.

This Month's Highlights

American Society of Nephrology — Mon, 31 Oct 2016 10:00:44 GMT-07:00

Mendelian Randomization as an Approach to Assess Causality Using Observational Data

Sekula, Peggy — Tue, 02 Aug 2016 06:05:11 GMT-07:00

Mendelian randomization refers to an analytic approach to assess the causality of an observed association between a modifiable exposure or risk factor and a clinically relevant outcome. It presents a valuable tool, especially when randomized controlled trials to examine causality are not feasible and observational studies provide biased associations because of confounding or reverse causality. These issues are addressed by using genetic variants as instrumental variables for the tested exposure: the alleles of this exposure–associated genetic variant are randomly allocated and not subject to reverse causation. This, together with the wide availability of published genetic associations to screen for suitable genetic instrumental variables make Mendelian randomization a time- and cost-efficient approach and contribute to its increasing popularity for assessing and screening for potentially causal associations. An observed association between the genetic instrumental variable and the outcome supports the hypothesis that the exposure in question is causally related to the outcome. This review provides an overview of the Mendelian randomization method, addresses assumptions and implications, and includes illustrative examples. We also discuss special issues in nephrology, such as inverse risk factor associations in advanced disease, and outline opportunities to design Mendelian randomization studies around kidney function and disease.

Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery

Leaf, David E. — Thu, 02 Jun 2016 05:35:03 GMT-07:00

Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.

Heme Oxygenase-1 Gene Polymorphisms—Toward Precision Medicine for AKI

Curtis, Lisa M. — Thu, 04 Aug 2016 05:44:09 GMT-07:00

Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy

Huang, Zhi Qiang — Thu, 10 Mar 2016 07:57:44 GMT-08:00

Autoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose–deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy.

Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in Patients

Nie, Mingzhu — Fri, 01 Apr 2016 07:44:03 GMT-07:00

Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole–cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2– and caveolin-1–mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan–deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study

Meyer, Timothy W. — Tue, 29 Mar 2016 07:00:02 GMT-07:00

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.

Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD

Poesen, Ruben — Thu, 26 May 2016 06:16:23 GMT-07:00

Colonic microbial metabolism substantially contributes to uremic solute production. p-Cresyl sulfate and indoxyl sulfate are the main representatives of solutes of microbial origin and also, protein-bound solutes, exhibiting high protein-binding affinity and dependence on tubular secretion. Phenylacetylglutamine is another microbial metabolite with high dependence on tubular secretion but low protein-binding affinity. The relevance of such solutes is unknown. Therefore, we prospectively followed 488 patients with CKD stages 1–5 and a measurement of serum phenylacetylglutamine by liquid chromatography-mass spectrometry. In a subgroup, we determined 24-hour urinary excretion as a surrogate of intestinal uptake as well as renal clearance of phenylacetylglutamine. We performed outcome analysis for mortality (51 events) and cardiovascular disease (75 events). Serum phenylacetylglutamine level correlated with 24-hour urinary excretion (rho=0.55; P<0.001) and clearance of phenylacetylglutamine (rho=−0.76; P<0.001). Phenylacetylglutamine clearance also correlated with eGFR (rho=0.84; P<0.001). Furthermore, serum phenylacetylglutamine level associated with mortality (hazard ratio per 1-SD increase, 1.77; 95% confidence interval, 1.22 to 2.57; P=0.003) and cardiovascular disease (hazard ratio, 1.79; 95% confidence interval, 1.32 to 2.41; P<0.001) after adjustment for age, sex, presence of diabetes mellitus, prior cardiovascular disease, and eGFR. Thus, serum phenylacetylglutamine level is elevated in patients with more advanced CKD and determined by intestinal uptake and renal clearance, and it is not fully accounted for by differences in eGFR. High serum phenylacetylglutamine level is a strong and independent risk factor for mortality and cardiovascular disease, suggesting the relevance of microbial metabolism and/or tubular dysfunction in CKD, irrespective of protein binding.

CKD Progression and Mortality among Hispanics and Non-Hispanics

Fischer, Michael J. — Thu, 05 May 2016 07:03:13 GMT-07:00

Although recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes.

Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties

Galgamuwa, Ramindhu — Wed, 09 Mar 2016 09:59:02 GMT-08:00

Cisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin.

Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells

Oosthuyzen, Wilna — Mon, 28 Mar 2016 06:04:45 GMT-07:00

Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo. We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.

Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria

Yu, Hao — Mon, 28 Mar 2016 06:04:45 GMT-07:00

Gain-of-function mutations of classic transient receptor potential channel 6 (TRPC6) were identified in familial FSGS, and increased expression of wild-type TRPC6 in glomeruli is observed in several human acquired proteinuric diseases. Synaptopodin, an actin binding protein that is important in maintaining podocyte function, is downregulated in various glomerular diseases. Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6. We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes. Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it. Mechanistically, synaptopodin–dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons. Overexpression of wild–type or FSGS–inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6–mediated calcium influx and induced apoptosis. In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6. Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice. Furthermore, administration of cyclosporin A reversed the LPS-induced increase in podocyte surface expression of TRPC6 in wild-type mice. Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction. Reducing TRPC6 surface levels may be a new approach to restoring podocyte function.

Mitochondrial Pathology and Glycolytic Shift during Proximal Tubule Atrophy after Ischemic AKI

Lan, Rongpei — Mon, 21 Mar 2016 09:47:59 GMT-07:00

During recovery by regeneration after AKI, proximal tubule cells can fail to redifferentiate, undergo premature growth arrest, and become atrophic. The atrophic tubules display pathologically persistent signaling increases that trigger production of profibrotic peptides, proliferation of interstitial fibroblasts, and fibrosis. We studied proximal tubules after ischemia-reperfusion injury (IRI) to characterize possible mitochondrial pathologies and alterations of critical enzymes that govern energy metabolism. In rat kidneys, tubules undergoing atrophy late after IRI but not normally recovering tubules showed greatly reduced mitochondrial number, with rounded profiles, and large autophagolysosomes. Studies after IRI of kidneys in mice, done in parallel, showed large scale loss of the oxidant–sensitive mitochondrial protein Mpv17L. Renal expression of hypoxia markers also increased after IRI. During early and late reperfusion after IRI, kidneys exhibited increased lactate and pyruvate content and hexokinase activity, which are indicators of glycolysis. Furthermore, normally regenerating tubules as well as tubules undergoing atrophy exhibited increased glycolytic enzyme expression and inhibitory phosphorylation of pyruvate dehydrogenase. TGF-β antagonism prevented these effects. Our data show that the metabolic switch occurred early during regeneration after injury and was reversed during normal tubule recovery but persisted and became progressively more severe in tubule cells that failed to redifferentiate. In conclusion, irreversibility of the metabolic switch, taking place in the context of hypoxia, high TGF-β signaling and depletion of mitochondria characterizes the development of atrophy in proximal tubule cells and may contribute to the renal pathology after AKI.

CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T Cells

Evers, Beatrix D.G. — Fri, 01 Apr 2016 07:44:02 GMT-07:00

Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3−/− mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy

Scheele, Wim — Mon, 25 Apr 2016 05:34:35 GMT-07:00

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.

The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy

Han, Seung Seok — Mon, 11 Apr 2016 05:50:19 GMT-07:00

TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

Endothelial Sphingosine 1‑Phosphate Receptor‑1 Mediates Protection and Recovery from Acute Kidney Injury

Perry, Heather M. — Wed, 09 Mar 2016 09:59:05 GMT-08:00

Epithelial and endothelial injury and a cascade of immune and interstitial cell activation in the kidney lead to AKI. After mild to moderate AKI, the epithelium can regenerate and restore kidney function, yet little is known about the endothelium during these repair processes. Sphingosine 1-phosphate receptor 1 (S1P1), a G protein–coupled receptor, is necessary for vascular homeostasis. Here, we used an inducible genetic approach in a mouse model of AKI, ischemia–reperfusion injury (IRI), to determine the temporal effects of endothelial S1P1 during AKI. Deletion of endothelial S1P1 before IRI exacerbated kidney injury and inflammation, and the delayed deletion of S1P1 after IRI prevented kidney recovery, resulting in chronic inflammation and progressive fibrosis. Specifically, S1P1 directly suppressed endothelial activation of leukocyte adhesion molecule expression and inflammation. Altogether, the data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery from AKI. Endothelial S1P1 may be a therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI.

Carbamylated Erythropoietin Outperforms Erythropoietin in the Treatment of AKI-on-CKD and Other AKI Models

Tögel, Florian E. — Wed, 16 Mar 2016 10:09:03 GMT-07:00

Erythropoietin (EPO) may be a beneficial tissue–protective cytokine. However, high doses of EPO are associate with adverse effects, including thrombosis, tumor growth, and hypertension. Carbamylated erythropoietin (CEPO) lacks both erythropoietic and vasoconstrictive actions. In this study, we compared the renoprotective, hemodynamic, and hematologic activities and survival effects of identical EPO and CEPO doses in rat models of clinically relevant AKI presentations, including ischemia-reperfusion–induced AKI superimposed on CKD (5000 U/kg EPO or CEPO; three subcutaneous injections) and ischemia-reperfusion–induced AKI in old versus young animals and male versus female animals (1000 U/kg EPO or CEPO; three subcutaneous injections). Compared with EPO therapy, CEPO therapy induced greater improvements in renal function and body weight in AKI on CKD animals, with smaller increases in hematocrit levels and similarly improved survival. Compared with EPO therapy in the other AKI groups, CEPO therapy induced greater improvements in protection and recovery of renal function and survival, with smaller increases in systolic BP and hematocrit levels. Overall, old or male animals had more severe loss in kidney function and higher mortality rates than young or female animals, respectively. Notably, mRNA and protein expression analyses confirmed the renal expression of the heterodimeric EPO receptor/CD131 complex, which is required for the tissue-protective effects of CEPO signaling. In conclusion, CEPO improves renal function, body and kidney weight, and survival in AKI models without raising hematocrit levels and BP as substantially as EPO. Thus, CEPO therapy may be superior to EPO in improving outcomes in common forms of clinical AKI.

Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease

Kröpelin, Tobias F. — Thu, 07 Apr 2016 06:41:13 GMT-07:00

Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per study visit. A confirmation of the end point or a requirement of a minimal percentage change in albuminuria from baseline seems unnecessary.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors

Nigwekar, Sagar U. — Thu, 14 Apr 2016 08:01:55 GMT-07:00

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273–2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Calcific Uremic Arteriolopathy Revisited

Jovanovich, Anna — Wed, 25 May 2016 06:24:10 GMT-07:00

HEMO Revisited: Why Kt/Vurea Only Tells Part of the Story

Meijers, Björn — Tue, 07 Jun 2016 07:46:17 GMT-07:00

Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal Allografts

Gorbacheva, Victoria — Mon, 28 Mar 2016 06:04:44 GMT-07:00

Despite advances in immunosuppression, antibody-mediated rejection is a serious threat to allograft survival. Alloreactive memory helper T cells can induce potent alloantibody responses and often associate with poor graft outcome. Nevertheless, the ability of memory T cells to elicit well characterized manifestations of antibody-mediated rejection has not been tested. We investigated helper functions of memory CD4 T cells in a mouse model of renal transplantation. Whereas the majority of unsensitized C57Bl/6 recipients spontaneously accepted fully MHC–mismatched A/J renal allografts, recipients containing donor–reactive memory CD4 T cells rapidly lost allograft function. Increased serum creatinine levels, high serum titers of donor-specific alloantibody, minimal T cell infiltration, and intense C4d deposition in the grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal antibody–mediated rejection in humans. IFNγ neutralization did not prevent the renal allograft rejection induced by memory helper T cells, and CD8 T cell depletion at the time of transplantation or depletion of both CD4 and CD8 T cells also did not prevent the renal allograft rejection induced by memory helper T cells starting at day 4 after transplantation. However, B cell depletion inhibited alloantibody generation and significantly extended allograft survival, indicating that donor-specific alloantibodies (not T cells) were the critical effector mechanism of renal allograft rejection induced by memory CD4 T cells. Our studies provide direct evidence that recipient T cell sensitization may result in antibody-mediated rejection of renal allografts and introduce a physiologically relevant animal model with which to investigate mechanisms of antibody-mediated rejection and novel therapeutic approaches for its prevention and treatment.

Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant Recipients

Badve, Sunil V. — Thu, 21 Jul 2016 06:25:39 GMT-07:00

Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine Ratio

Herrington, William — Wed, 21 Sep 2016 10:03:54 GMT-07:00

High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S. Veterans

Bowe, Benjamin — Thu, 11 Aug 2016 08:21:49 GMT-07:00

Supportive Care: Integration of Patient-Centered Kidney Care to Manage Symptoms and Geriatric Syndromes

Davison, Sara N. — Wed, 10 Aug 2016 06:57:42 GMT-07:00

Dialysis care is often associated with poor outcomes including low quality of life (QOL). To improve patient-reported outcomes, incorporation of the patient’s needs and perspective into the medical care they receive is essential. This article provides a framework to help clinicians integrate symptom assessment and other measures such as QOL and frailty scores into a clinical approach to the contemporary supportive care of patients with advanced CKD. This approach involves (1) defining our understanding of kidney supportive care, patient-centered dialysis, and palliative dialysis; (2) understanding and recognizing common symptoms associated with advanced CKD; (3) discussing the concepts of physical function, frailty, and QOL and their role in CKD; and (4) identifying the structural and process barriers that may arise when patient-centered dialysis is being introduced into clinical practice.

Chronic Kidney Disease and Risk for Gastrointestinal Bleeding in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Ishigami, Junichi — Thu, 11 Aug 2016 08:21:50 GMT-07:00

All Things Complement

Thurman, Joshua M. — Thu, 23 Jun 2016 08:13:32 GMT-07:00

The complement (C) cascade is an ancient system of proteins whose primary role is to initiate and modulate immune responses. During C activation, circulating proteins are cleaved and nascent cleavage fragments participate in a broad range of downstream innate and adaptive immune functions. Although the majority of these functions are either homeostatic or protective, a large body of experimental and clinical evidence also highlights a central role for the C system in the pathogenesis of many types of glomerular disease. From classic pathway activation in lupus nephritis to alternative pathway dysregulation in C3 glomerulopathy, our understanding of the spectrum of C involvement in kidney disease has expanded greatly in recent years. However, the characteristics that make the glomerulus so uniquely susceptible to C-mediated injury are not fully understood, and this remains an area of ongoing investigation. Several C inhibitors have been approved for clinical use, and additional C inhibitory drugs are in development. The use of these drugs in patients with kidney disease will expand our understanding of the benefits and limitations of C inhibition.

Supportive Care: Economic Considerations in Advanced Kidney Disease

Morton, Rachael L. — Wed, 10 Aug 2016 06:57:42 GMT-07:00

Kidney supportive care describes multiple interventions for patients with advanced CKD that focus on improving the quality of life and addressing what matters most to patients. This includes shared decision making and aligning treatment plans with patient goals through advance care planning and providing relief from pain and other distressing symptoms. Kidney supportive care is an essential component of quality care throughout the illness trajectory. However, in the context of limited health care resources, evidence of its cost-effectiveness is required to support decisions regarding appropriate resource allocation. We review the literature and outline the evidence gaps and particular issues associated with measuring the costs, benefits, and cost-effectiveness of kidney supportive care. We find evidence that the dominant evaluative framework of a cost per quality–adjusted life year may not be suitable for evaluations in this context and that relevant outcomes may include broader measures of patient wellbeing, having care aligned with treatment preferences, and family satisfaction with the end of life care experience. To improve the evidence base for the cost-effectiveness of kidney supportive care, large prospective cohort studies are recommended to collect data on both resource use and health outcomes and should include patients who receive conservative kidney management without dialysis. Linkage to administrative datasets, such as Medicare, Hospital Episode Statistics, and the Pharmaceutical Benefits Scheme for prescribed medicines, can provide a detailed estimate of publicly funded resource use and reduce the burden of data collection for patients and families. Longitudinal collection of quality of life and functional status should be added to existing cohort or kidney registry studies. Interventions that improve health outcomes for people with advanced CKD, such as kidney supportive care, not only have the potential to improve quality of life, but also may reduce the high costs associated with unwanted hospitalization and intensive medical treatments.

Renal Survival in Patients with Collapsing Compared with Not Otherwise Specified FSGS

Laurin, Louis-Philippe — Thu, 21 Jul 2016 06:25:40 GMT-07:00

Predictors of Initiation for Predialysis Arteriovenous Fistula

Al-Balas, Alian — Wed, 14 Sep 2016 07:17:53 GMT-07:00

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Bushinsky, David A. — Tue, 27 Sep 2016 07:05:56 GMT-07:00

Supportive Care: Meeting the Needs of Patients with Advanced Chronic Kidney Disease

Davison, Sara N. — Fri, 07 Oct 2016 10:00:31 GMT-07:00

The Influence of Processing and Storage Conditions on Renal Protein Biomarkers

Giesen, Callen — Wed, 21 Sep 2016 10:03:54 GMT-07:00

Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome

Banh, Tonny H.M. — Thu, 21 Jul 2016 06:25:40 GMT-07:00

A Prospective, Randomized Trial of Routine Duplex Ultrasound Surveillance on Arteriovenous Fistula Maturation

Han, Ahram — Wed, 24 Aug 2016 04:42:02 GMT-07:00

Longitudinal Changes in Protein Carbamylation and Mortality Risk after Initiation of Hemodialysis

Kalim, Sahir — Thu, 21 Jul 2016 06:25:38 GMT-07:00

Can We Predict the Unpredictable after Vascular Access Creation?

Polkinghorne, Kevan R. — Wed, 14 Sep 2016 07:17:53 GMT-07:00

Supportive Care: Comprehensive Conservative Care in End-Stage Kidney Disease

Murtagh, Fliss E.M. — Wed, 10 Aug 2016 06:57:42 GMT-07:00

Comprehensive conservative (nondialytic) kidney care is widely recognized and delivered but until recently, has not been clearly defined. We provide a clear definition of comprehensive conservative care. This includes interventions to delay progression of kidney disease and minimize complications as well as detailed communication, shared decision making, advance care planning, and psychologic and family support. It does not include dialysis. Limited epidemiologic evidence from Australia and Canada indicates that, for every new person diagnosed with ESRD who receives dialysis or transplant, there is one new person who is managed conservatively (either actively or not). For older patients (those >75 or 80 years old) who have higher levels of comorbidity (such as diabetes and heart disease) and poorer functional status, the survival advantage of dialysis may be limited, and comprehensive conservative management may be considered; however, robust comparative evidence remains limited. Considerations of symptoms, quality of life, and hospital-free days are as or sometimes more important for patients and families than survival. There is some evidence that communication about possible conservative management options is generally insufficient, even where comprehensive conservative care pathways are already established. Symptom control and the cost-effectiveness of interventions are addressed in the companion papers within this Moving Points in Nephrology series. There is almost no evidence about which models of care and which interventions might be most beneficial in this population; future research on these areas is much needed. Meanwhile, consistency in definition of comprehensive conservative care and basing interventions on existing evidence about survival, symptoms, quality of life, and experience will maximize patient-centered and holistic care.

The Role of RRT in Hyperammonemic Patients

Gupta, Shruti — Thu, 19 May 2016 06:54:28 GMT-07:00

Hyperammonemia is an important cause of cerebral edema in both adults with liver failure and children with inborn errors of metabolism. There are few studies that have analyzed the role of extracorporeal dialysis in reducing blood ammonia levels in the adult population. Furthermore, there are no firm guidelines about when to implement RRT, because many of the conditions that are characterized by hyperammonemia are extremely rare. In this review of existing literature on RRT, we present the body’s own mechanisms for clearing ammonia as well as the dialytic properties of ammonia. We review the available literature on the use of continuous venovenous hemofiltration, peritoneal dialysis, and hemodialysis in neonates and adults with conditions characterized by hyperammonemia and discuss some of the controversies that exist over selecting one modality over another.

Patiromer–an Oral Calcium-Loaded Potassium Binder: Kalirrhea with Calciuresis

Emmett, Michael — Tue, 27 Sep 2016 07:05:57 GMT-07:00

Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

Tellier, Stéphanie — Thu, 21 Jul 2016 06:25:38 GMT-07:00

RRT in AKI: Start Early or Wait?

Liu, Kathleen D. — Mon, 26 Sep 2016 07:34:50 GMT-07:00

Practice Change Is Needed for Dialysis Decision Making with Older Adults with Advanced Kidney Disease

Scherer, Jennifer S. — Thu, 22 Sep 2016 06:35:09 GMT-07:00

Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 2000–2011

Wong, Susan P.Y. — Thu, 22 Sep 2016 06:35:09 GMT-07:00

Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones

Ferraro, Pietro Manuel — Thu, 21 Jul 2016 06:25:40 GMT-07:00

Supportive Care: Communication Strategies to Improve Cultural Competence in Shared Decision Making

Brown, Edwina A. — Wed, 10 Aug 2016 06:57:43 GMT-07:00

Historic migration and the ever–increasing current migration into Western countries have greatly changed the ethnic and cultural patterns of patient populations. Because health care beliefs of minority groups may follow their religion and country of origin, inevitable conflict can arise with decision making at the end of life. The principles of truth telling and patient autonomy are embedded in the framework of Anglo–American medical ethics. In contrast, in many parts of the world, the cultural norm is protection of the patient from the truth, decision making by the family, and a tradition of familial piety, where it is dishonorable not to do as much as possible for parents. The challenge for health care professionals is to understand how culture has enormous potential to influence patients’ responses to medical issues, such as healing and suffering, as well as the physician-patient relationship. Our paper provides a framework of communication strategies that enhance crosscultural competency within nephrology teams. Shared decision making also enables clinicians to be culturally competent communicators by providing a model where clinicians and patients jointly consider best clinical evidence in light of a patient’s specific health characteristics and values when choosing health care. The development of decision aids to include cultural awareness could avoid conflict proactively, more productively address it when it occurs, and enable decision making within the framework of the patient and family cultural beliefs.

Supportive Care: Time to Change Our Prognostic Tools and Their Use in CKD

Couchoud, Cécile — Wed, 10 Aug 2016 06:57:41 GMT-07:00

In using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist’s recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients’ values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients’ priorities in development of new scores. Delivering patient-centered care requires an understanding of patients’ priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients’ health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health–related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient–centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely to entail for the individual patient in terms of likely quality and quantity of life according to the patient’s values and goals and not just the possibility of life prolongation.

Measurement Error as Alternative Explanation for the Observation that CrCl/GFR Ratio is Higher at Lower GFR

Zhang, Xuehan — Wed, 03 Aug 2016 05:54:00 GMT-07:00

Silent Cerebral Microbleeds and Longitudinal Risk of Renal and Cardiovascular Events in Patients with CKD

Shima, Hideaki — Mon, 27 Jun 2016 06:49:04 GMT-07:00

Risk Factors for and Outcomes of Catheter-Associated Peritonitis in Children: The SCOPE Collaborative

Sethna, Christine B. — Thu, 23 Jun 2016 08:13:30 GMT-07:00

Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants

Askenazi, David J. — Thu, 28 Jul 2016 05:59:10 GMT-07:00

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

Chen, Chunbo — Thu, 18 Aug 2016 08:15:53 GMT-07:00

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Zhang, Yi-miao — Thu, 23 Jun 2016 08:13:33 GMT-07:00

Inflammation and Progression of CKD: The CRIC Study

Amdur, Richard L. — Thu, 23 Jun 2016 08:13:32 GMT-07:00

Creatinine–Based and Cystatin C–Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant Recipients

Keddis, Mira T. — Thu, 23 Jun 2016 08:13:30 GMT-07:00

The Players: Cells Involved in Glomerular Disease

Kitching, A. Richard — Tue, 12 Apr 2016 08:25:44 GMT-07:00

Glomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others. In addition to those cells intrinsic to the glomerulus, leukocytes patrol the glomerulus in health and mediate injury in disease. Distinct leukocyte types and subsets are present, with some being involved in different ways in an individual glomerular disease. Cells of the innate and adaptive immune systems are important, directing systemic immune and inflammatory responses, locally mediating injury, and potentially dampening inflammation and facilitating repair. The advent of new genetic and molecular techniques, and new disease models means that we better understand both the basic biology of the glomerulus and the pathogenesis of glomerular disease. This understanding should lead to better diagnostic techniques, biomarkers, and predictors of prognosis, disease severity, and relapse. With this knowledge comes the promise of better therapies in the future, directed toward halting pathways of injury and fibrosis, or interrupting the underlying pathophysiology of the individual diseases that lead to significant and progressive glomerular disease.

Assisted Peritoneal Dialysis as an Alternative to In-Center Hemodialysis

Brown, Edwina A. — Wed, 27 Jul 2016 06:04:24 GMT-07:00

Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal Significance

Hogan, Jonathan J. — Thu, 14 Jul 2016 06:32:39 GMT-07:00

The monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an “onco-nephrologic” approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.

Variation in Patients’ Awareness of CKD according to How They Are Asked

Tuot, Delphine S. — Thu, 23 Jun 2016 08:13:34 GMT-07:00

Introduction: Glomerular Disease Update for the Clinician

Nester, Carla M. — Wed, 07 Sep 2016 10:00:36 GMT-07:00

Lower Extremity Permanent Dialysis Vascular Access

Parekh, Vishal B. — Fri, 27 May 2016 06:24:11 GMT-07:00

Hemodialysis remains the most commonly used RRT option around the world. Technological advances, superior access to care, and better quality of care have led to overall improvement in survival of patients on long-term hemodialysis. Maintaining a functioning upper extremity vascular access for a prolonged duration continues to remain a challenge for dialysis providers. Frequently encountered difficulties in clinical practice include (1) a high incidence of central venous catheter–related central vein stenosis and (2) limited options for creating a functioning upper extremity permanent arteriovenous access. Lack of surgical skills, fear of complications, and limited involvement of the treating nephrologists in the decision-making process are some of the reasons why lower extremity permanent dialysis access remains an infrequently used option. Similar to upper extremity vascular access options, lower extremity arteriovenous fistula remains a preferred access over arteriovenous synthetic graft. The use of femoral tunneled catheter as a long-term access should be avoided as far as possible, especially with the availability of newer graft-catheter hybrid devices. Our review provides a summary of clinical evidence published in surgical, radiology, and nephrology literature highlighting the pros and cons of different types of lower extremity permanent dialysis access.

Adjusting the 17β–Estradiol-to-Androgen Ratio Ameliorates Diabetic Nephropathy

Inada, Akari — Thu, 03 Mar 2016 10:59:05 GMT-08:00

Diabetes is manifested predominantly in males in experimental models, and compelling evidence suggests that 17β-estradiol (E2) supplementation improves hyperglycemia in humans. We previously generated a severely diabetic transgenic (Tg) mouse model by β-cell–specific overexpression of inducible cAMP early repressor (ICER) and found that male but not female ICER-Tg mice exhibit sustained hyperglycemia and develop major clinical and pathologic features of human diabetic nephropathy (DN). Thus, we hypothesized that differences in circulating hormone levels have a key role in determining susceptibility to diabetes. Here, we examined whether DN in male ICER-Tg mice is rescued by adjusting the androgen-to-E2 ratio to approximate that in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX), E2 pellet implantation, or both. E2 pellet implantation at an early stage of DN with or without ORX caused a rapid drop in blood glucose and a dramatic increase in β-cell number, and it markedly inhibited DN progression [namely, E2 reduced glomerulosclerosis, collagen IV deposition and albuminuria, and prevented hyperfiltration]. Furthermore, E2 pellet implantation was more effective than ORX alone and induced a remarkable improvement, even when initiated at advanced-stage DN. In contrast, induction of normoglycemia by islet transplant in ICER-Tg mice eliminated albuminuria but was less effective than E2+ORX in reducing glomerulosclerosis or collagen IV deposition and hyperfiltration. These findings indicate that E2 treatment is effective, even after establishment of DN, whereas glucose normalization alone does not improve sclerotic lesions. We propose that E2 intervention is a potential therapeutic option for DN.

Prorenin Receptor, a Necessary Component in Urine Concentration Mechanism

Jensen, Boye L. — Wed, 20 Apr 2016 06:42:31 GMT-07:00

Sex Differences and Renal Protection: Keeping in Touch with Your Feminine Side

Garovic, Vesna D. — Tue, 17 May 2016 07:14:26 GMT-07:00

ESRD Payment Reform: First Do No Harm

Shen, Jenny I. — Tue, 29 Mar 2016 07:00:05 GMT-07:00

Proton Pump Inhibitors and CKD

Moledina, Dennis G. — Thu, 14 Apr 2016 08:01:56 GMT-07:00

Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition

Nikolaeva, Svetlana — Thu, 07 Apr 2016 06:41:15 GMT-07:00

The circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1lox/lox/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD+-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition.

MicroRNA-196a/b Mitigate Renal Fibrosis by Targeting TGF-β Receptor 2

Meng, Jiao — Thu, 03 Mar 2016 10:59:03 GMT-08:00

Organ-specific microRNAs have essential roles in maintaining normal organ function. However, the microRNA profile of the kidney and the role of microRNAs in modulating renal function remain undefined. We performed an unbiased assessment of the genome-wide microRNA expression profile in 14 mouse organs using Solexa deep sequencing and found that microRNA-196a (miR-196a) and miR-196b are selectively expressed in kidney, with 74.37% of mouse total miR-196a and 73.19% of mouse total miR-196b distributed in the kidneys. We confirmed the predominant expression of miR-196a/b in mouse and human kidney, particularly in the glomeruli and tubular epithelium, by quantitative RT-PCR and in situ hybridization assays. During unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis, renal miR-196a/b levels rapidly decreased. Elevation of renal miR-196a/b expression by hydrodynamic-based delivery of a miR-196a/b–expressing plasmid before or shortly after UUO significantly downregulated profibrotic proteins, including collagen 1 and α-smooth muscle actin, and mitigated UUO-induced renal fibrosis. In contrast, depletion of renal miR-196a/b by miR-196a/b antagomirs substantially aggravated UUO-induced renal fibrosis. Mechanistic studies further identified transforming growth factor beta receptor II (TGFβR2) as a common target of miR-196a and miR-196b. Decreasing miR-196a/b expression in human HK2 cells strongly activated TGF-β–Smad signaling and cell fibrosis; whereas increasing miR-196a/b levels in mouse primary cultured tubular epithelial cells inhibited TGF-β–Smad signaling. In the UUO model, miR-196a/b silenced TGF-β–Smad signaling, decreased the expression of collagen 1 and α-smooth muscle actin, and attenuated renal fibrosis. Our findings suggest that elevating renal miR-196a/b levels may be a novel therapeutic strategy for treating renal fibrosis.

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4

Wang, Fei — Mon, 21 Mar 2016 09:47:58 GMT-07:00

Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4. Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.

Blockade of Orai1 Store-Operated Calcium Entry Protects against Renal Fibrosis

Mai, Xiaoyi — Thu, 03 Mar 2016 10:59:07 GMT-08:00

Evidence supports an important role of Ca2+ release-activated Ca2+ channel protein 1 (Orai1)-mediated Ca2+ entry in the development of renal fibrosis, a common pathologic feature of CKDs that lead to ESRD, but the molecular mechanisms remain unclear. We determined the role of Orai1 calcium channel in renal fibrosis induced by high-fat diet and by unilateral ureteral obstruction. Mouse kidneys with fibrosis had higher levels of Orai1 protein expression than did kidneys without fibrosis. In vivo knockdown of Orai1 with adenovirus harboring Orai1–short hairpin RNA or inhibition of Orai1 with SKF96365 dramatically prevented renal fibrosis and significantly decreased protein expression of fibronectin, α‑smooth muscle actin, and TGF‑β1 in the kidney cortex of ApoE–/– mice on a high-fat diet and in the obstructed kidneys of mice with unilateral ureteral obstruction. Compared with kidney biopsy specimens of patients with glomerular minimal change disease, those of patients with fibrotic nephropathy had higher expression levels of Orai1. In cultured human proximal tubule epithelial cells (HK2), knockdown of Orai1 Ca2+ channel with adenovirus–Orai1–short hairpin RNA markedly inhibited TGF-β1–induced intracellular Ca2+ influx and phosphorylation of smad2/3. Knockdown or blockade of the Orai1 Ca2+ channel in HK2 cells also prevented epithelial-to-mesenchymal transition induced by TGF‑β1. In conclusion, blockade of the Orai1 Ca2+ channel prevented progression of renal fibrosis in mice, likely by suppressing smad2/3 phosphorylation and TGF-β1–induced epithelial-to-mesenchymal transition. These results render the Orai1 Ca2+ channel a potential therapeutic target against renal fibrosis.

Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli

Puelles, Victor G. — Mon, 14 Mar 2016 06:33:06 GMT-07:00

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD

Xie, Yan — Thu, 14 Apr 2016 08:01:55 GMT-07:00

The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2 blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial

Bodonyi-Kovacs, Gabor — Thu, 03 Mar 2016 10:58:59 GMT-08:00

Apolipoprotein L-1 (APOL1) high–risk alleles and the glutathione-S-transferase-μ1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high–risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high– or low–risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m2 decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P≤0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low–risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high–risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low–risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high–risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high–risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high–risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups.

Predicting Individual Renal Allograft Outcomes Using Risk Models with 1-Year Surveillance Biopsy and Alloantibody Data

Gonzales, Manuel Moreno — Wed, 09 Mar 2016 09:59:01 GMT-08:00

The ability to predict outcomes for individual patients would be a significant advance for not only counseling, but also identifying those for whom interventions may be needed. The goals of this study were to validate an existing risk prediction score that incorporates easily obtainable clinical factors and determine if histologic findings at 1-year surveillance biopsy and/or serum donor–specific alloantibody status could improve predictability of graft loss by 5 years. We retrospectively studied 1465 adults who received a solitary kidney transplant between January of 1999 and December of 2008 and had sufficiently detailed 5-year follow-up data for modeling. In this cohort, the Birmingham risk model (incorporating recipient factors at 1 year, including age, sex, ethnicity, renal function, proteinuria, and prior acute rejection) predicted death–censored and overall graft survival (c statistics =0.84 and 0.78, respectively). The presence of glomerulitis or chronic interstitial fibrosis (g and ci scores by Banff, respectively) on 1-year biopsy specimens independently correlated with graft loss by 5 years. Adding these variables to the model for death–censored graft loss increased predictability (c statistic =0.90), improved calibration (ability to stratify risk from high to low), and reclassified risk of failure in 29% of patients. Adding the presence of donor-specific alloantibody at 1 year did not improve predictability or reclassification but did improve calibration marginally. We conclude that, at 1 year after kidney transplant, a risk model of graft survival that incorporates clinical factors and histologic findings at surveillance biopsy is highly predictive of individual risk and well calibrated.

Polymorphisms in α-Defensin–Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux

Schwaderer, Andrew L. — Thu, 03 Mar 2016 10:59:01 GMT-08:00

The contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real–time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk.

Fine Mapping Implicates a Deletion of CFHR1 and CFHR3 in Protection from IgA Nephropathy in Han Chinese

Xie, Jingyuan — Thu, 03 Mar 2016 10:59:06 GMT-08:00

An intronic variant at the complement factor H (CFH) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations. We investigated whether the causal sequence variant resides in the CFH gene or the neighboring complement factor H–related 1 (CFHR1) gene and CFHR3, which harbor an 84-kb combined deletion (CFHR3,1Δ) in linkage disequilibrium with rs6677604. Imputation of 1000 Genomes Project data did not suggest new causal single–nucleotide variants within the CFH cluster. We next performed copy number analysis across the CFH locus in two independent Han Chinese case-control cohorts (combined n=3581). The CFHR3,1Δ and rs6677604-A alleles were rare (4.4% in patients and 7.1% in controls) and in strong linkage disequilibrium with each other (r2=0.95); of these alleles, CFHR3,1Δ associated more significantly with decreased risk of IgAN (odds ratio [OR], 0.56; 95% confidence interval [95% CI], 0.46 to 0.70; P=8.5 × 10−8 versus OR, 0.61; 95% CI, 0.50 to 0.75; P=1.6 × 10−6 for rs6677604-A). Moreover, CFHR3,1Δ explained all of the association signal at rs6677604 and remained significant after conditioning on rs6677604 genotype (P=0.01). Exploratory analyses of clinical and histopathologic parameters using the Oxford classification criteria revealed a suggestive association of CFHR3,1Δ with reduced tubulointerstitial injury (OR, 0.46; 95% CI, 0.25 to 0.79). These data indicate that dysregulated activity of the alternative complement pathway contributes to IgAN pathogenesis in both Asians and Europeans and implicate CFHR3,1Δ as the functional allele at this locus.

Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy

Qin, Hua-Zhang — Thu, 17 Mar 2016 07:24:37 GMT-07:00

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb− (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb−/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.

YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis

Szeto, Stephen G. — Wed, 09 Mar 2016 09:59:00 GMT-08:00

Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-β. In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-β–induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-β/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-β signaling and renal fibrogenesis.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform

Chertow, Glenn M. — Thu, 25 Feb 2016 01:28:07 GMT-08:00

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005–2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: −0.24 [−0.08 to −0.37] for stroke, −2.43 [−1.35 to −3.70] for VTE, and −0.77 [−0.28 to −1.27] for heart failure), although non–ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

Pragmatic, Precision Medicine Approaches for Dialysis Vascular Access Dysfunction: Challenges and Opportunities

Roy-Chaudhury, Prabir — Tue, 30 Aug 2016 06:16:50 GMT-07:00

What Is the Correct Approach for Comparing GFR by Different Methods across Levels of GFR?

Rule, Andrew D. — Wed, 03 Aug 2016 05:53:59 GMT-07:00

Urinary Angiotensinogen: A Promising Biomarker of AKI Progression in Acute Decompensated Heart Failure: What Does It Mean?

Wysocki, Jan — Thu, 18 Aug 2016 08:15:53 GMT-07:00

Correction

American Society of Nephrology — Mon, 15 Aug 2016 04:05:39 GMT-07:00

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate

Tanriover, Bekir — Thu, 30 Jun 2016 07:01:42 GMT-07:00

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis

Block, Geoffrey A. — Thu, 23 Jun 2016 08:13:29 GMT-07:00

Alport Syndrome in Women and Girls

Savige, Judy — Fri, 10 Jun 2016 06:44:56 GMT-07:00

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling, informed of their reproductive options, and monitored closely during pregnancy for the development of hypertension.

Preoperative Vascular Medial Fibrosis and Arteriovenous Fistula Development

Shiu, Yan-Ting — Tue, 30 Aug 2016 06:16:51 GMT-07:00

Chemistry Testing on Plasma Versus Serum Samples in Dialysis Patients: Clinical and Quality Improvement Implications

Carey, Roger Neill — Mon, 16 May 2016 08:36:54 GMT-07:00

Plasma samples collected in tubes containing separator gels have replaced serum samples for most chemistry tests in many hospital and commercial laboratories. Use of plasma samples for blood tests in the dialysis population eliminates delays in sample processing while waiting for clotting to complete, laboratory technical issues associated with fibrin formation, repeat sample collection, and patient care issues caused by delay of results because of incompletely clotted specimens. Additionally, a larger volume of plasma is produced than serum for the same amount of blood collected. Plasma samples are also acceptable for most chemical tests involved in the care of patients with ESRD. This information becomes very important when United States regulatory requirements for ESRD inadvertently limit the type of sample that can be used for government reporting, quality assessment, and value–based payment initiatives. In this narrative, we summarize the renal community experience and how the subsequent resolution of the acceptability of phosphorus levels measured from serum and plasma samples may have significant implications in the country’s continued development of a value–based Medicare ESRD Quality Incentive Program.

Hospitalization Rates for Patients on Assisted Peritoneal Dialysis Compared with In-Center Hemodialysis

Oliver, Matthew J. — Wed, 27 Jul 2016 06:04:24 GMT-07:00

Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney Diseases

Cukor, Daniel — Thu, 19 May 2016 06:54:28 GMT-07:00

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is “Patient Centered-Research”, in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases.

Functional and Cognitive Impairment, Frailty, and Adverse Health Outcomes in Older Patients Reaching ESRD—A Systematic Review

Kallenberg, Marije H. — Fri, 24 Jun 2016 06:51:08 GMT-07:00

Urinary Soluble CD163 in Active Renal Vasculitis

O’Reilly, Vincent P. — Thu, 03 Mar 2016 10:58:59 GMT-08:00

A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.

IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition

Oruc, Zeliha — Fri, 29 Jan 2016 09:12:17 GMT-08:00

IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch–Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen–free environment had less IgA deposition. However, serum IgA of specific pathogen–free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain–deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post–translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.

TRPC6 G757D Loss-of-Function Mutation Associates with FSGS

Riehle, Marc — Thu, 18 Feb 2016 07:35:11 GMT-08:00

FSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of FSGS have been linked to mutations in the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene encoding a nonselective cation channel. Most of these TRPC6 mutations cause a gain-of-function phenotype, leading to calcium–triggered podocyte cell death, but the underlying molecular mechanisms are unclear. We studied the molecular effect of disease-related mutations using tridimensional in silico modeling of tetrameric TRPC6. Our results indicated that G757 is localized in a domain forming a TRPC6-TRPC6 interface and predicted that the amino acid exchange G757D causes local steric hindrance and disruption of the channel complex. Notably, functional characterization of model interface domain mutants suggested a loss-of-function phenotype. We then characterized 19 human FSGS–related TRPC6 mutations, the majority of which caused gain-of-function mutations. However, five mutations (N125S, L395A, G757D, L780P, and R895L) caused a loss-of-function phenotype. Coexpression of wild-type TRPC6 and TRPC6 G757D, mimicking heterozygosity observed in patients, revealed a dominant negative effect of TRPC6 G757D. Our comprehensive analysis of human disease–causing TRPC6 mutations reveals loss of TRPC6 function as an additional concept of hereditary FSGS and provides molecular insights into the mechanism responsible for the loss-of-function phenotype of TRPC6 G757D in humans.

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Tinckam, Kathryn J. — Wed, 17 Feb 2016 07:14:32 GMT-08:00

Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all–cause or death–censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death–censored graft loss, particularly in patients with detectable panel–reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all–cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death–censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.

The Search for a Biomarker of Relapse in ANCA-Associated Vasculitis

Free, Meghan E. — Mon, 09 May 2016 06:33:55 GMT-07:00

MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic Nephropathy

Zhao, Binghai — Tue, 02 Feb 2016 06:15:34 GMT-08:00

Diabetic nephropathy (DN) is a frequent and severe complication of diabetes that is structurally characterized by glomerular basement membrane thickening, extracellular matrix accumulation, and destabilization of podocyte foot processes. MicroRNAs (miRNAs) are dysregulated in DN, but identification of the specific miRs involved remains incomplete. Here, we confirm that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of miR-23b compared with those of their nondiabetic counterparts. Furthermore, exposure to high glucose downregulated miR-23b in cultured kidney cells. In contrast, renal expression of Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), a putative miR-23b target, increased in DN. In vitro, overexpression of miR-23b decreased, and inhibition of miR-23b increased, G3BP2 expression levels. Bioinformatics analysis also revealed p53 binding sites in the miR-23b promoter; in vitro inhibition of p53 or the upstream p38 mitogen-activated protein kinase (p38MAPK) upregulated miR-23b expression in high-glucose conditions. In turn, inhibition of G3BP2 or overexpression of miR-23b downregulated p53 and p38MAPK expression in high-glucose conditions. In vivo, overexpression of miR-23b or inhibition of p53 in db/db mice reversed hyperalbuminuria and kidney fibrosis, whereas miR-23b antagomir treatment promoted renal fibrosis and increased albuminuria in wild-type mice. These data suggest that hyperglycemia regulates pathogenic processes in DN through an miR-23b/G3BP2 feedback circuit involving p38MAPK and p53. In conclusion, these results reveal a role for miR-23b in DN and indicate a novel potential therapeutic target.

Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney Disease

Heyer, Christina M. — Thu, 28 Jan 2016 09:48:39 GMT-08:00

Autosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height–adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.

Coordinated Control of ENaC and Na+,K+-ATPase in Renal Collecting Duct

Feraille, Eric — Tue, 17 May 2016 07:14:27 GMT-07:00

Tubular reabsorption of filtered sodium is tightly controlled to maintain body volume homeostasis. The rate of sodium transport by collecting duct (CD) cells varies widely in response to dietary sodium intake, GFR, circulating hormones, neural signals, and local regulatory factors. Reabsorption of filtered sodium by CD cells occurs via a two-step process. First, luminal sodium crosses the apical plasma membrane along its electrochemical gradient through epithelial sodium channels (ENaC). Intracellular sodium is then actively extruded into the interstitial space by the Na+,K+-ATPase located along the basolateral membrane. Mismatch between sodium entry and exit induces variations in sodium intracellular concentration and cell volume that must be maintained within narrow ranges for control of vital cell functions. Therefore, renal epithelial cells display highly coordinated apical and basolateral sodium transport rates. We review evidence from experiments conducted in vivo and in cultured cells that indicates aldosterone and vasopressin, the two major hormones regulating sodium reabsorption by CD, generate a coordinated stimulation of apical ENaC and basolateral Na+,K+-ATPase. Moreover, we discuss evidence suggesting that variations in sodium entry per se induce a coordinated change in Na+,K+-ATPase activity through the signaling of protein kinases such as protein kinase A and p38 mitogen-activated protein kinase.

Social Determinants of Racial Disparities in CKD

Norton, Jenna M. — Fri, 13 May 2016 09:11:45 GMT-07:00

Significant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.

This Month's Highlights

American Society of Nephrology — Wed, 31 Aug 2016 10:01:11 GMT-07:00

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

Anders, Hans-Joachim — Thu, 11 Aug 2016 08:00:58 GMT-07:00

Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1β and of the alarmin IL-1α. Dying cells release IL-1α also, independently of the inflammasome. Both IL-1α and IL-1β ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1α/IL-β-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1α/β regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1α/IL-β-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency–approved IL-1–neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1α/IL-β-IL-1R system in kidney disease should be further explored.

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Zhai, Ya-Ling — Fri, 29 Jan 2016 09:12:12 GMT-08:00

A recent genome–wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H–related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants. The distribution of rare variants in CFHR5 in patients with IgAN differed significantly from that in controls (P=0.002). Among the rare variants, in silico programs predicted nine as potential functional variants, which we then assessed in functional assays. Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity (CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D: 127.25%±1.75%; P<0.001), whereas another recombinant CFHR5 (c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%±0.57%; P<0.001). Our study found that rare variants in CFHR5 may contribute to the genetic susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene.

IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA Nephropathy

Lechner, Sebastian M. — Fri, 05 Feb 2016 06:25:47 GMT-08:00

IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti–hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the α1KI‑CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1‑P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1‑P (1–10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1–sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b+ infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1‑P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1‑P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.

Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3−

Zhou, Yuehan — Tue, 02 Feb 2016 06:15:34 GMT-08:00

Regulation of blood pH—critical for virtually every facet of life—requires that the renal proximal tubule (PT) adjust its rate of H+ secretion (nearly the same as the rate of HCO3− reabsorption, JHCO3) in response to changes in blood [CO2] and [HCO3−]. Yet CO2/HCO3− sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-γ (RPTPγ) that are consistent with binding of extracellular CO2 or HCO3− facilitate monitoring of blood CO2/HCO3− concentrations. We now report that PTs express RPTPγ on blood-facing membranes. Moreover, RPTPγ deletion in mice eliminated the CO2 and HCO3− sensitivities of JHCO3 as well as the normal defense of blood pH during whole-body acidosis. Thus, RPTPγ appears to be a novel extracellular CO2/HCO3− sensor critical for pH homeostasis.

Recombinant N–Terminal Slit2 Inhibits TGF-β–Induced Fibroblast Activation and Renal Fibrosis

Yuen, Darren A. — Thu, 11 Feb 2016 05:52:03 GMT-08:00

Fibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-β. Here, we examined whether Slit2 also controls TGF-β–induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N–terminal fragment of Slit2 inhibited TGF-β–induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C–terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.

Glucocorticoid-Regulated Kinase: Linking Azotemia and Muscle Wasting in CKD

Menon, Madhav C. — Fri, 08 Apr 2016 05:34:14 GMT-07:00

Candidate Surrogate End Points for ESRD after AKI

Grams, Morgan E. — Mon, 08 Feb 2016 06:17:30 GMT-08:00

AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%–40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.

Inhibition of EGF Receptor Blocks the Development and Progression of Peritoneal Fibrosis

Wang, Li — Thu, 17 Dec 2015 07:44:13 GMT-08:00

Inhibitors of EGF receptor (EGFR) have antifibrotic effects in several organs, but the effect of these inhibitors on the development of peritoneal fibrosis is unknown. Here, we explored the therapeutic effect of gefitinib, a specific inhibitor of EGFR, on the development and progression of peritoneal fibrosis in a rat model. Daily intraperitoneal injections of chlorhexidine gluconate induced peritoneal fibrosis, indicated by thickening of the submesothelial area with an accumulation of collagen fibrils and activation of myofibroblasts, accompanied by time-dependent phosphorylation of EGFR. Administration of gefitinib immediately after injury prevented the onset of peritoneal fibrosis and delayed administration after the onset of peritoneal fibrosis halted fibrosis progression. Gefitinib treatment abrogated the increased phosphorylation of EGFR, Smad3, signal transducer and activator of transcription 3, and NF-κB during peritoneal fibrosis; it also inhibited the accompanying overproduction of TGF-β1 and proinflammatory cytokines and the infiltration of macrophages to the injured peritoneum. Moreover, gefitinib significantly reduced the peritoneal increase of CD31-positive blood vessels and vascular EGF-positive cells after injury. Finally, gefitinib also attenuated high glucose–induced peritoneal fibrosis in rats and abrogated TGF-β1–induced phosphorylation of Smad3 and the epithelial-to-mesenchymal transition of cultured human peritoneal mesothelial cells. These results demonstrate that EGFR contributes to peritoneal fibrosis, inflammation, and angiogenesis, suggesting that EGFR inhibitors may have therapeutic potential in attenuating peritoneal fibrosis.

Erratum

American Society of Nephrology — Wed, 31 Aug 2016 10:01:11 GMT-07:00

Erratum

American Society of Nephrology — Wed, 31 Aug 2016 10:01:11 GMT-07:00

Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base Homeostasis

Soleimani, Manoocher — Mon, 18 Apr 2016 07:55:56 GMT-07:00

Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD

de Boer, Ian H. — Thu, 28 Jan 2016 09:48:37 GMT-08:00

Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m2) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, −0.7; 95% confidence interval, −1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, −85; 95% confidence interval, −160 to −10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.

Race, APOL1 Risk, and eGFR Decline in the General Population

Grams, Morgan E. — Thu, 10 Mar 2016 07:57:45 GMT-08:00

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987–1989 (baseline) to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th–90th percentile) unadjusted eGFR decline was 1.5 (1.0–2.2) ml/min per 1.73 m2 per year for whites, 2.1 (1.4–3.1) ml/min per 1.73 m2 per year for blacks with APOL1 low-risk status, and 2.3 (1.5–3.5) ml/min per 1.73 m2 per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.

Challenges in Rare Variant Association Studies for Complex Kidney Traits: CFHR5 and IgA Nephropathy

Kiryluk, Krzysztof — Tue, 17 May 2016 07:14:26 GMT-07:00

Renal Function Profile in White Kidney Donors: The First 4 Decades

Ibrahim, Hassan N. — Wed, 17 Feb 2016 07:14:33 GMT-08:00

Previous studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean±SD follow-up of 16.6±11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m2, and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m2 or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m2 or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77–1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors.

Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin–Mediated Kidney Injury

van Swelm, Rachel P.L. — Fri, 29 Jan 2016 09:12:14 GMT-08:00

Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin–induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI.

Dynamin–Related Protein 1 Deficiency Improves Mitochondrial Fitness and Protects against Progression of Diabetic Nephropathy

Ayanga, Bernard A. — Fri, 29 Jan 2016 09:12:13 GMT-08:00

Mitochondrial fission has been linked to the pathogenesis of diabetic nephropathy (DN). However, how mitochondrial fission affects progression of DN in vivo is unknown. Here, we report the effect of conditional podocyte–specific deletion of dynamin-related protein 1 (Drp1), an essential component of mitochondrial fission, on the pathogenesis and progression of DN. Inducible podocyte–specific deletion of Drp1 in diabetic mice decreased albuminuria and improved mesangial matrix expansion and podocyte morphology. Ultrastructure analysis revealed a significant increase in fragmented mitochondria in the podocytes of wild–type diabetic mice but a marked improvement in mitochondrial structure in Drp1-null podocytes of diabetic mice. When isolated from diabetic mice and cultured in high glucose, Drp1-null podocytes had more elongated mitochondria and better mitochondrial fitness associated with enhanced oxygen consumption and ATP production than wild-type podocytes. Furthermore, administration of a pharmacologic inhibitor of Drp1, Mdivi1, significantly blunted mitochondrial fission and rescued key pathologic features of DN in mice. Taken together, these results provide novel correlations between mitochondrial morphology and the progression of DN and point to Drp1 as a potential therapeutic target in DN.

Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells

Arcolino, Fanny Oliveira — Thu, 03 Mar 2016 10:58:58 GMT-08:00

In humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31–36 weeks of gestational age and characterized isolated cells using a single–cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte–specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p-glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.

MicroRNA-489 Induction by Hypoxia–Inducible Factor–1 Protects against Ischemic Kidney Injury

Wei, Qingqing — Mon, 14 Mar 2016 06:33:08 GMT-07:00

MicroRNAs have been implicated in ischemic AKI. However, the specific microRNA species that regulates ischemic kidney injury remains unidentified. Our previous microarray analysis revealed microRNA-489 induction in kidneys of mice subjected to renal ischemia-reperfusion. In this study, we verified the induction of microRNA-489 during ischemic AKI in mice and further examined the underlying mechanisms. Hypoxia–inducible factor–1α deficiency associated with diminished microRNA-489 induction in cultured rat proximal tubular cells subjected to hypoxia and kidney tissues of mice after renal ischemia-reperfusion injury. Moreover, genomic analysis revealed that microRNA-489 is intronic in the calcitonin receptor gene, and chromatin immunoprecipitation assays showed increased binding of hypoxia–inducible factor–1 to a specific site in the calcitonin receptor gene promoter after hypoxia. Inhibition of microRNA-489 increased apoptosis in renal tubular cells after ATP depletion injury in vitro, whereas microRNA-489 mimics mediated protection. In mice, inhibition of microRNA-489 enhanced tubular cell death and ischemic AKI without significantly affecting tubular cell proliferation. Deep sequencing identified 417 mRNAs that were recruited to the RNA–induced silencing complex by microRNA-489. Of the identified mRNAs, 127 contain microRNA-489 targeting sites, and of those, 18 are involved in the cellular stress response, including the poly(ADP-ribose) polymerase 1 gene implicated in ischemic kidney injury. Sequence analysis and in vitro studies validated poly(ADP-ribose) polymerase 1 as a microRNA-489 target. Together, these results suggest that microRNA-489 is induced via hypoxia–inducible factor–1 during ischemic AKI to protect kidneys by targeting relevant genes.

Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3

Luo, Jinlong — Mon, 15 Feb 2016 06:04:51 GMT-08:00

Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid–regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD–induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N-myc downstream–regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD–induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD.

Inorganic Phosphate Activates the AKT/mTORC1 Pathway and Shortens the Life Span of an α‑Klotho–Deficient Model

Kawai, Masanobu — Fri, 12 Feb 2016 08:26:53 GMT-08:00

Inorganic phosphate (Pi) has been implicated in the pathogenesis of accelerated aging; however, the underlying mechanisms remain elusive. Herein, we demonstrated in cultured cells and in vivo that increased levels of extracellular Pi activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway by suppressing membrane-bound phosphatase and tensin homolog (PTEN) levels in a manner requiring the sodium-dependent Pi transporter PiT‑1. High levels of extracellular Pi also led to phosphorylation of Ser/Thr clusters in the C‑terminal tail of PTEN, which has been shown to dissociate PTEN from the membrane. Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic α‑Klotho–deficient (Kl−/−) mice. Dietary correction of hyperphosphatemia or treatment with rapamycin also rescued the brown adipose tissue dysfunction and oxidative damage observed in Kl−/− mice. Furthermore, rapamycin treatment partially rescued these effects and extended the life span when Kl−/− mice were maintained on a high-phosphate diet. Finally, rapamycin reduced circulating Pi levels in Kl−/− mice, apparently by decreasing the localization of sodium-dependent Pi transport protein 2a at the renal brush border membrane. Therefore, the activation of mTORC1 may create a vicious loop that exacerbates the retention of Pi, which in turn may enhance oxidative damage and ultimately shorten the life span of Kl−/− mice. These results demonstrate that Pi has important roles in the aging process, and the blockade of mTORC1 may have therapeutic potential for premature aging-like symptoms associated with hyperphosphatemia.

The Risk of Major Hemorrhage with CKD

Molnar, Amber O. — Thu, 28 Jan 2016 09:48:40 GMT-08:00

New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002–2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m2) and urine albumin-to-creatinine ratio (ACR; >300, 30–300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m2 had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.

Far Upstream Element-Binding Protein 1 Binds the 3′ Untranslated Region of PKD2 and Suppresses Its Translation

Zheng, Wang — Tue, 02 Feb 2016 06:15:35 GMT-08:00

Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3′ untranslated region (3′UTR) of PKD2 mRNA inhibits luciferase protein expression. We then identified nucleotides 691–1044, which we called 3FI, as the 3′UTR fragment necessary for repressing the expression of luciferase or PKD2 in this system. Using a pull-down assay and mass spectrometry we identified far upstream element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 expression and alleviated fish tail curling caused by morpholino-mediated KD of PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding protein 1, indicating a link to the translation initiation complex. These results show that FUBP1 binds 3FI in the PKD2 3′UTR to inhibit PKD2 translation, regulating zebrafish disease phenotypes associated with PKD2 KD.

Tubular Epithelial NF-κB Activity Regulates Ischemic AKI

Markó, Lajos — Thu, 28 Jan 2016 09:48:42 GMT-08:00

NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type–specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)–induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed that IRI induced widespread NF-κB activation in renal tubular epithelia and in interstitial cells that peaked 2–3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBαΔN in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF-κB–dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBαΔN-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF-κB activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.

A Novel Extrinsic Pathway for the Unfolded Protein Response in the Kidney

Mami, Iadh — Thu, 28 Jan 2016 09:48:41 GMT-08:00

The ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1α, a key activator of the unfolded protein response. The transcription factors spliced X-box–binding protein 1 and p65, which are activated by inositol-requiring enzyme 1α upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL-6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AKI.

Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD

Yamamoto-Nonaka, Kanae — Thu, 28 Jan 2016 09:48:43 GMT-08:00

Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte–specific CD–knockout mice that developed proteinuria at 5 months of age and ESRD by 20–22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7– and lysosome–associated membrane glycoprotein 1–positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte–specific CD–knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c–positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.

Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular Cells

Venkatareddy, Madhusudan — Fri, 29 Jan 2016 09:12:15 GMT-08:00

The mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34–deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux.

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

Chan, Chang-Yien — Tue, 07 Jun 2016 07:13:32 GMT-07:00

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial

Nadkarni, Girish N. — Tue, 17 May 2016 06:53:02 GMT-07:00

Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart Study

Afkarian, Maryam — Thu, 23 Jun 2016 08:13:31 GMT-07:00

Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease

Canney, Mark — Mon, 11 Jul 2016 10:26:42 GMT-07:00

Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on Dialysis

Chang, Tara I. — Mon, 27 Jun 2016 06:49:03 GMT-07:00

Geovariation in Fracture Risk among Patients Receiving Hemodialysis

Wetmore, James B. — Tue, 07 Jun 2016 07:13:32 GMT-07:00

Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study

Mc Causland, Finnian R. — Fri, 22 Jul 2016 06:30:48 GMT-07:00

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee, Timmy — Mon, 11 Jul 2016 10:26:43 GMT-07:00

Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.

Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK

Tin, Adrienne — Thu, 26 May 2016 06:28:31 GMT-07:00

New Insights into Dialysis Vascular Access: Introduction

Allon, Michael — Mon, 08 Aug 2016 10:00:40 GMT-07:00

New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes

Vazquez-Padron, Roberto I. — Mon, 11 Jul 2016 10:26:42 GMT-07:00

Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.

Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress Nephropathy

Glaser, Jason — Thu, 05 May 2016 06:45:48 GMT-07:00

Climate change has led to significant rise of 0.8°C–0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.

Update on Ethical Issues in Pediatric Dialysis: Has Pediatric Dialysis Become Morally Obligatory?

Wightman, Aaron G. — Fri, 01 Apr 2016 06:30:13 GMT-07:00

Improvements in pediatric dialysis over the past 50 years have made the decision to proceed with dialysis straightforward for the majority of pediatric patients. For certain groups, however, such as children with multiple comorbid conditions, children and families with few social and economic resources, and neonates and infants, the decision of whether to proceed with dialysis remains much more controversial. In this review, we will examine the best available data regarding the outcomes of dialysis in these populations and analyze the important ethical considerations that should guide decisions regarding dialysis for these patients. We conclude that providers must continue to follow a nuanced and individualized approach in decision making for each child and to recognize that, regardless of the decision reached about dialysis, there is a continued duty to care for patients and families to maximize the remaining quality of their lives.

Correction

American Society of Nephrology — Mon, 27 Jun 2016 06:49:04 GMT-07:00

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones

Vezzoli, Giuseppe — Thu, 09 Jun 2016 07:34:38 GMT-07:00

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome

Kamiyoshi, Naohiro — Wed, 08 Jun 2016 06:36:35 GMT-07:00

New Insights into Dialysis Vascular Access: What Is the Optimal Vascular Access Type and Timing of Access Creation in CKD and Dialysis Patients?

Woo, Karen — Mon, 11 Jul 2016 10:26:42 GMT-07:00

Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient’s ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts.

Peripherally Inserted Central Catheters and Hemodialysis Outcomes

McGill, Rita L. — Thu, 23 Jun 2016 08:13:28 GMT-07:00

Does Changing the Volume Matter? The Relationship of Urine Volume and Dialysis Intensity

Federspiel, Christine K. — Fri, 22 Jul 2016 06:30:48 GMT-07:00

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors

Courbebaisse, Marie — Tue, 17 May 2016 06:53:01 GMT-07:00

Clustering of Anti-GBM Disease: Clues to an Environmental Trigger?

McAdoo, Stephen P. — Mon, 11 Jul 2016 10:26:43 GMT-07:00

Antihypertensive Medication in Patients Pre- and Postdialysis: Still Hazy After All These Years

Cohen, Jordana B. — Mon, 27 Jun 2016 06:49:03 GMT-07:00

Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT

Shotwell, Matthew S. — Thu, 19 May 2016 06:54:26 GMT-07:00

Nephrologists Versus Peripherally Inserted Central Catheters: Are the PICCs Winning?

Kalloo, Sean — Thu, 23 Jun 2016 08:13:34 GMT-07:00

Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival Factors

Johnson, Richard J. — Thu, 09 Jun 2016 07:35:14 GMT-07:00

Climate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways.

Parathyroidectomy or Calcimimetic to Treat Hypercalcemia after Kidney Transplantation?

Fukagawa, Masafumi — Fri, 15 Jan 2016 06:30:47 GMT-08:00

The End of Racial Disparities in Kidney Transplantation? Not So Fast!

Williams, Winfred W. — Mon, 07 Mar 2016 06:35:45 GMT-08:00

B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

Delville, Marianne — Wed, 23 Dec 2015 06:57:21 GMT-08:00

FSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7–1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7–1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7–1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7–1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7–1 blockade did not induce FSGS remission after transplant in our study.

Reduced Racial Disparity in Kidney Transplant Outcomes in the United States from 1990 to 2012

Purnell, Tanjala S. — Thu, 04 Feb 2016 06:57:28 GMT-08:00

Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990–2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.

Caspase-1, but Not Caspase-3, Promotes Diabetic Nephropathy

Shahzad, Khurrum — Mon, 01 Feb 2016 01:53:27 GMT-08:00

Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity. Accordingly, analysis of gene expression data in the Nephromine database revealed persistently elevated glomerular expression of inflammasome markers (NLRP3, CASP1, PYCARD, IL-18, IL-1β), but not of apoptosis markers (CASP3, CASP7, PARP1), in patients with and murine models of dNP. In vitro, increased levels of markers of inflammasome activation (Nlrp3, caspase-1 cleavage) preceded those of markers of apoptosis activation (caspase-3 and -7, PARP1 cleavage) in glucose-stressed podocytes. Finally, caspase-3 deficiency did not protect mice from dNP, whereas both homozygous and hemizygous caspase-1 deficiency did. Hence, these results suggest caspase-3-dependent cell death has a negligible effect, whereas caspase-1-dependent inflammasome activation has a crucial function in the establishment of dNP. Furthermore, small molecules targeting caspase-1 or inflammasome activation may be a feasible therapeutic approach in dNP.

This Month's Highlights

American Society of Nephrology — Fri, 29 Jul 2016 10:00:54 GMT-07:00

IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI

Feng, Guowei — Thu, 11 Feb 2016 05:52:02 GMT-08:00

Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan–IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan–IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.

αKlotho Mitigates Progression of AKI to CKD through Activation of Autophagy

Shi, Mingjun — Wed, 23 Dec 2015 06:57:20 GMT-08:00

AKI confers increased risk of progression to CKD. αKlotho is a cytoprotective protein, the expression of which is reduced in AKI, but the relationship of αKlotho expression level to AKI progression to CKD has not been studied. We altered systemic αKlotho levels by genetic manipulation, phosphate loading, or aging and examined the effect on long-term outcome after AKI in two models: bilateral ischemia-reperfusion injury and unilateral nephrectomy plus contralateral ischemia-reperfusion injury. Despite apparent initial complete recovery of renal function, both types of AKI eventually progressed to CKD, with decreased creatinine clearance, hyperphosphatemia, and renal fibrosis. Compared with wild-type mice, heterozygous αKlotho–hypomorphic mice (αKlotho haploinsufficiency) progressed to CKD much faster, whereas αKlotho-overexpressing mice had better preserved renal function after AKI. High phosphate diet exacerbated αKlotho deficiency after AKI, dramatically increased renal fibrosis, and accelerated CKD progression. Recombinant αKlotho administration after AKI accelerated renal recovery and reduced renal fibrosis. Compared with wild-type conditions, αKlotho deficiency and overexpression are associated with lower and higher autophagic flux in the kidney, respectively. Upregulation of autophagy protected kidney cells in culture from oxidative stress and reduced collagen 1 accumulation. We propose that αKlotho upregulates autophagy, attenuates ischemic injury, mitigates renal fibrosis, and retards AKI progression to CKD.

Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against Podocytopathy

Zhou, Sijie — Tue, 08 Dec 2015 01:27:46 GMT-08:00

Evidence suggests that the glycogen synthase kinase 3 (GSK3)–dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3β (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3β in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3β mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3β by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3β-regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies.

Nephrin Tyrosine Phosphorylation Is Required to Stabilize and Restore Podocyte Foot Process Architecture

New, Laura A. — Fri, 22 Jan 2016 07:55:46 GMT-08:00

Podocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series of interdigitating actin–rich foot processes. Positioned between adjacent projections is a unique cell junction known as the slit diaphragm, which is physically connected to the actin cytoskeleton via the transmembrane protein nephrin. Evidence indicates that tyrosine phosphorylation of the intracellular tail of nephrin initiates signaling events, including recruitment of cytoplasmic adaptor proteins Nck1 and Nck2 that regulate actin cytoskeletal dynamics. Nephrin tyrosine phosphorylation is altered in human and experimental renal diseases characterized by pathologic foot process remodeling, prompting the hypothesis that phosphonephrin signaling directly influences podocyte morphology. To explore this possibility, we generated and analyzed knockin mice with mutations that disrupt nephrin tyrosine phosphorylation and Nck1/2 binding (nephrinY3F/Y3F mice). Homozygous nephrinY3F/Y3F mice developed progressive proteinuria accompanied by structural changes in the filtration barrier, including podocyte foot process effacement, irregular thickening of the glomerular basement membrane, and dilated capillary loops, with a similar but later onset phenotype in heterozygous animals. Furthermore, compared with wild-type mice, nephrinY3F/Y3F mice displayed delayed recovery in podocyte injury models. Profiling of nephrin tyrosine phosphorylation dynamics in wild-type mice subjected to podocyte injury indicated site-specific differences in phosphorylation at baseline, injury, and recovery, which correlated with loss of nephrin-Nck1/2 association during foot process effacement. Our results define an essential requirement for nephrin tyrosine phosphorylation in stabilizing podocyte morphology and suggest a model in which dynamic changes in phosphotyrosine-based signaling confer plasticity to the podocyte actin cytoskeleton.

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI

Zhang, Jiandong — Thu, 07 Jan 2016 06:07:30 GMT-08:00

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue–specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell Carcinoma

Hu, Susie L. — Wed, 09 Mar 2016 09:58:59 GMT-08:00

Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel–Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist’s tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist’s tumor.

Increased Synthesis of Liver Erythropoietin with CKD

de Seigneux, Sophie — Tue, 12 Jan 2016 06:13:50 GMT-08:00

Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0–20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6–9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.

Hepatitis C Virus Infection in Chronic Kidney Disease

Ladino, Marco — Tue, 19 Apr 2016 05:54:06 GMT-07:00

Soon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct–acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of >90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.

Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

Coca, Steven G. — Mon, 28 Dec 2015 06:30:33 GMT-08:00

Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.

MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney Disease

Lakhia, Ronak — Thu, 17 Dec 2015 07:44:14 GMT-08:00

Autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4. Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.

Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis

Takaori, Koji — Wed, 23 Dec 2015 06:57:24 GMT-08:00

AKI increases the risk of developing CKD, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers features of CKD. We generated a novel mouse model to induce proximal tubule–specific adjustable injury by inducing the expression of diphtheria toxin (DT) receptor with variable prevalence in proximal tubules. Administration of high-dose DT in mice expressing the DT receptor consistently caused severe proximal tubule–specific injury associated with interstitial fibrosis and reduction of erythropoietin production. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis, inflammation, glomerulosclerosis, and atubular glomeruli. DT–induced proximal tubule–specific injury also triggered distal tubule injury. Furthermore, injured tubular cells cocultured with fibroblasts stimulated induction of extracellular matrix and inflammatory genes. These results support the existence of proximal-distal tubule crosstalk and crosstalk between tubular cells and fibroblasts. Overall, our data provide evidence that proximal tubule injury triggers several features of CKD and that the severity and frequency of proximal tubule injury determines the progression to CKD.

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Cruzado, Josep M. — Tue, 08 Dec 2015 01:27:44 GMT-08:00

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open–label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

Transcription Factor Hepatocyte Nuclear Factor–1β Regulates Renal Cholesterol Metabolism

Aboudehen, Karam — Mon, 28 Dec 2015 06:30:34 GMT-08:00

HNF-1β is a tissue–specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β–regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin–like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism.

Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport

Terker, Andrew S. — Mon, 28 Dec 2015 06:30:35 GMT-08:00

Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide–sensitive Na+-Cl− cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney–specific MR–knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.

Past Decline Versus Current eGFR and Subsequent ESRD Risk

Kovesdy, Csaba P. — Fri, 11 Dec 2015 08:20:59 GMT-08:00

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta–analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of −6 versus 0 ml/min per 1.73 m2 per year over the previous 3 years (a decline of 18 ml/min per 1.73 m2 versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m2 (a difference of 20 ml/min per 1.73 m2) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m2.

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark, David M.J. — Fri, 11 Dec 2015 08:20:58 GMT-08:00

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual–level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <−5 ml/min per 1.73 m2 per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m2 per year, a slope of −6 ml/min per 1.73 m2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m2 per year also associated with higher all–cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Tin, Adrienne — Thu, 21 Jan 2016 05:59:20 GMT-08:00

Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis

Ok, Ercan — Wed, 23 Dec 2015 06:57:20 GMT-08:00

Exposure to high Ca concentrations may influence the development of low–turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Early Changes in Kidney Distribution under the New Allocation System

Massie, Allan B. — Thu, 17 Dec 2015 07:44:15 GMT-08:00

The Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18–40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51–60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long-term outcomes.

Intragraft Blood Dendritic Cell Antigen-1–Positive Myeloid Dendritic Cells Increase during BK Polyomavirus–Associated Nephropathy

Yapici, Ünsal — Wed, 23 Dec 2015 06:57:22 GMT-08:00

Although both polyomavirus infection and T cell–mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus–associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1+ (BDCA-1+) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1+ mDCs localized in proximity to the polyomavirus–infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1+ mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1+ mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.

Do You Want to Ditch Sodium? Meet Nitric Oxide Synthase 1β at the Macula Densa

Jose, Pedro A. — Mon, 22 Feb 2016 05:49:58 GMT-08:00

Modified Hydrogels to Enhance Cellular Therapy for AKI: A Translational Challenge

Gooch, Anna — Thu, 11 Feb 2016 05:52:02 GMT-08:00

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

Bhatt, Kirti — Tue, 08 Dec 2015 01:27:43 GMT-08:00

Inflammation has a critical role in the pathogenesis of diabetic complications, including diabetic nephropathy (DN). MicroRNAs have recently emerged as important regulators of DN. However, the role of microRNAs in the regulation of inflammation during DN is poorly understood. Here, we examined the in vivo role of microRNA-146a (miR-146a), a known anti-inflammatory microRNA, in the pathogenesis of DN. In a model of streptozotocin-induced diabetes, miR-146a−/− mice showed significantly exacerbated proteinuria, renal macrophage infiltration, glomerular hypertrophy, and fibrosis relative to the respective levels in control wild-type mice. Diabetes-induced upregulation of proinflammatory and profibrotic genes was significantly greater in the kidneys of miR-146a−/− than in the kidneys of wild-type mice. Notably, miR-146a expression increased in both peritoneal and intrarenal macrophages in diabetic wild-type mice. Mechanistically, miR-146a deficiency during diabetes led to increased expression of M1 activation markers and suppression of M2 markers in macrophages. Concomitant with increased expression of proinflammatory cytokines, such as IL-1β and IL-18, markers of inflammasome activation also increased in the macrophages of diabetic miR-146a−/− mice. These studies suggest that in early DN, miR-146a upregulation exerts a protective effect by downregulating target inflammation-related genes, resulting in suppression of proinflammatory and inflammasome gene activation. Loss of this protective mechanism in miR-146a−/− mice leads to accelerated DN. Taken together, these results identify miR-146a as a novel anti-inflammatory noncoding RNA modulator of DN.

Severe Salt–Losing Syndrome and Hyperkalemia Induced by Adult Nephron–Specific Knockout of the Epithelial Sodium Channel α-Subunit

Perrier, Romain — Wed, 23 Dec 2015 06:57:27 GMT-08:00

Systemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt–losing syndrome caused by loss-of-function mutations of the amiloride–sensitive epithelial sodium channel (ENaC) and characterized by neonatal life–threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na+/Cl− cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron–specific αENaC-knockout mice (Scnn1aPax8/LC1) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC–mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC–mediated salt–losing PHA-1 phenotype.

Macula Densa Nitric Oxide Synthase 1β Protects against Salt-Sensitive Hypertension

Lu, Yan — Tue, 08 Dec 2015 01:27:47 GMT-08:00

Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, β-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1β expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1β expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1β mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1α-knockout (NOS1αKO) mice. Compared with control mice, mice with macula densa–specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1β is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.

A Novel Three–Dimensional Human Peritubular Microvascular System

Ligresti, Giovanni — Fri, 11 Dec 2015 08:21:00 GMT-08:00

Human kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional HKMEC-specific microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.

Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging Technique

Vuiblet, Vincent — Fri, 18 Dec 2015 08:08:52 GMT-08:00

Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier–transform infrared (FTIR) imaging–based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label–free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.

Metabolism, Protein Binding, and Renal Clearance of Microbiota–Derived p-Cresol in Patients with CKD

Poesen, Ruben — Fri, 15 Apr 2016 09:07:55 GMT-07:00

Predictors and Outcomes of Health–Related Quality of Life in Adults with CKD

Porter, Anna C. — Tue, 31 May 2016 06:42:03 GMT-07:00

Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD

Sun, Jia — Wed, 08 Jun 2016 06:36:34 GMT-07:00

Bone Disease after Kidney Transplantation

Bouquegneau, Antoine — Mon, 15 Feb 2016 06:59:31 GMT-08:00

Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.

Atrial Fibrillation and Risk of ESRD in Adults with CKD

Bansal, Nisha — Tue, 12 Apr 2016 08:25:44 GMT-07:00

Carotid Intima-Media Thickness and Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) Study

Pang, Yuanjie — Tue, 12 Apr 2016 08:25:45 GMT-07:00

Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD

Doyon, Anke — Thu, 16 Jun 2016 06:46:44 GMT-07:00

American Society of Nephrology Quiz and Questionnaire 2015: ESRD/RRT

Lok, Charmaine E. — Tue, 19 Apr 2016 07:00:29 GMT-07:00

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. During the 2015 meeting, the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid-base disorders, glomerular disease, ESRD and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cellphone application containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then, the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.

Tuning into Qualitative Research—A Channel for the Patient Voice

Tong, Allison — Tue, 31 May 2016 06:42:02 GMT-07:00

A Thematic Synthesis of the Experiences of Adults Living with Hemodialysis

Reid, Claire — Tue, 31 May 2016 06:42:03 GMT-07:00

High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients

Deger, Serpil Muge — Wed, 08 Jun 2016 06:36:35 GMT-07:00

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults

Bowling, C. Barrett — Mon, 18 Apr 2016 06:49:46 GMT-07:00

Long–Term Renal Outcomes after Cisplatin Treatment

Latcha, Sheron — Tue, 12 Apr 2016 08:25:46 GMT-07:00

Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients

Locatelli, Francesco — Mon, 16 May 2016 08:36:55 GMT-07:00

The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron–based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron–based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients.

Studying Muscle Protein Turnover in CKD

Garibotto, Giacomo — Wed, 08 Jun 2016 06:36:33 GMT-07:00

Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care Initiative

Wetmore, James B. — Tue, 22 Mar 2016 06:45:46 GMT-07:00

The past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infection-related and non–infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care.

Health–Related Quality of Life in CKD—Advancing Patient-Centered Research to Transform Patient Care

Powe, Neil R. — Tue, 31 May 2016 06:42:03 GMT-07:00

The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Review

van Loon, Ismay N. — Tue, 26 Apr 2016 07:08:56 GMT-07:00

Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States

Kim, Sun Moon — Mon, 06 Jun 2016 07:11:51 GMT-07:00

Effects of Stenting for Atherosclerotic Renal Artery Stenosis on eGFR and Predictors of Clinical Events in the CORAL Trial

Tuttle, Katherine R. — Wed, 25 May 2016 06:12:32 GMT-07:00

Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health

Scales, Charles D. — Thu, 10 Mar 2016 06:57:18 GMT-08:00

Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost–conscious care environment.

Parathyroidectomy: Complex Decisions about a Complex Procedure

Wetmore, James B. — Mon, 06 Jun 2016 07:11:51 GMT-07:00

Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences

Ma, Terry King-Wing — Mon, 06 Jun 2016 07:11:52 GMT-07:00

Does Renal Artery Stenting Prevent Clinical Events?

Textor, Stephen C. — Wed, 25 May 2016 06:12:33 GMT-07:00

Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus

de Groot, Theun — Mon, 16 Nov 2015 02:09:39 GMT-08:00

To reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.

Unlocking the Value of Variation in CKD Prevalence

Black, Corri — Tue, 29 Dec 2015 05:40:10 GMT-08:00

Utility of Prostate Cancer Screening in Kidney Transplant Candidates

Vitiello, Gerardo A. — Wed, 23 Dec 2015 06:57:24 GMT-08:00

Screening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)–based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55–69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.

Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United States

Mehrotra, Rajnish — Thu, 10 Dec 2015 12:36:22 GMT-08:00

Home dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n=162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.

Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific Antibodies

Willicombe, Michelle — Fri, 27 Nov 2015 06:38:39 GMT-08:00

The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy–free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor–specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.

Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial

Bansal, Nisha — Wed, 04 Nov 2015 10:27:52 GMT-08:00

Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver–type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.

Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial Embolization

Suwabe, Tatsuya — Mon, 30 Nov 2015 03:23:17 GMT-08:00

In patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], −6.10; 95% CI, −9.04 to −3.16; P<0.001), age (RC, −0.82; 95% CI, −1.03 to −0.60; P<0.001), dialysis duration (RC, −0.10; 95% CI, −0.18 to −0.03; P<0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P<0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P<0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.

This Month's Highlights

American Society of Nephrology — Thu, 30 Jun 2016 10:00:56 GMT-07:00

Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus

Mamenko, Mykola — Mon, 16 Nov 2015 02:09:37 GMT-08:00

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca2+) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca2+ levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca2+ mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca2+ levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.

Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion

Jackson, Edwin K. — Mon, 16 Nov 2015 02:09:40 GMT-08:00

A positional isomer of 3′,5′-cAMP, 2′,3′-cAMP, is produced by kidneys in response to energy depletion, and renal 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) metabolizes 2′,3′-cAMP to 2′-AMP; 2′,3′-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) –induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase−/−) versus wild-type (WT) mice using a unique two–kidney, hanging–weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 2′,3′-cAMP to 2′-AMP in CNPase−/− mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced 14C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase–associated lipocalin. IR did not affect these parameters in CNPase−/− mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase−/− mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone–sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/mitophagy in injured CNPase−/− mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria.

Enhancer of Zeste Homolog 2 Inhibition Attenuates Renal Fibrosis by Maintaining Smad7 and Phosphatase and Tensin Homolog Expression

Zhou, Xiaoxu — Wed, 23 Dec 2015 06:57:26 GMT-08:00

Enhancer of zeste homolog 2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. However, the role of EZH2 in renal fibrogenesis remains unexplored. In this study, we found high expression of EZH2 and H3K27me3 in cultured renal fibroblasts and fibrotic kidneys from mice with unilateral ureteral obstruction and humans with CKD. Pharmacologic inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) or GSK126 or siRNA-mediated silencing of EZH2 inhibited serum- and TGFβ1-induced activation of renal interstitial fibroblasts in vitro, and 3-DZNeP administration abrogated deposition of extracellular matrix proteins and expression of α-smooth muscle actin in the obstructed kidney. Injury to the kidney enhanced Smad7 degradation, Smad3 phosphorylation, and TGFβ receptor 1 expression, and 3-DZNeP administration prevented these effects. 3-DZNeP also suppressed phosphorylation of the renal EGF and PDGFβ receptors and downstream signaling molecules signal transducer and activator of transcription 3 and extracellular signal–regulated kinase 1/2 after injury. Moreover, EZH2 inhibition increased the expression of phosphatase and tensin homolog (PTEN), a protein previously associated with dephosphorylation of tyrosine kinase receptors in the injured kidney and serum–stimulated renal interstitial fibroblasts. Finally, blocking PTEN with SF1670 largely diminished the inhibitory effect of 3-DZNeP on renal myofibroblast activation. These results uncovered the important role of EZH2 in mediating the development of renal fibrosis by downregulating expression of Smad7 and PTEN, thus activating profibrotic signaling pathways. Targeted inhibition of EZH2, therefore, could be a novel therapy for treating CKD.

Idiopathic Retroperitoneal Fibrosis

Vaglio, Augusto — Tue, 09 Feb 2016 06:25:19 GMT-08:00

Idiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell–depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases.

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Thaunat, Olivier — Fri, 12 Feb 2016 08:26:54 GMT-08:00

The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor–specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor–specific antibody generation at the individual level.

Overcoming Barriers in Kidney Health—Forging a Platform for Innovation

Linde, Peter G. — Thu, 28 Apr 2016 06:19:54 GMT-07:00

Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.

Inhibitor of NFκB Kinase Subunit 2 Blockade Hinders the Initiation but Aggravates the Progression of Crescentic GN

Gotot, Janine — Mon, 16 Nov 2015 02:09:38 GMT-08:00

The NFκB transcription factor family facilitates the activation of dendritic cells (DCs) and CD4+ T helper (Th) cells, which are important for protective adaptive immunity. Inappropriate activation of these immune cells may cause inflammatory disease, and NFκB inhibitors are promising anti–inflammatory drug candidates. Here, we investigated whether inhibiting the NFκB–inducing kinase IKK2 can attenuate crescentic GN, a severe DC– and Th cell–dependent kidney inflammatory disease. Prophylactic pharmacologic IKK2 inhibition reduced DC and Th cell activation and ameliorated nephrotoxic serum–induced GN in mice. However, therapeutic IKK2 inhibition during ongoing disease aggravated the nephritogenic immune response and disease symptoms. This effect resulted from the renal loss of regulatory T cells, which have been shown to protect against crescentic GN and which require IKK2. In conclusion, although IKK2 inhibition can suppress the induction of nephritogenic immune responses in vivo, it may aggravate such responses in clinically relevant situations, because it also impairs regulatory T cells and thereby, unleashes preexisting nephritogenic responses. Our findings argue against using IKK2 inhibitors in chronic GN and perhaps, other immune–mediated diseases.

Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage

Suzuki, Takehiro — Wed, 25 Nov 2015 04:42:11 GMT-08:00

Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid–resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin–induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I–IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.

The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes

Siddiqi, Ferhan S. — Tue, 03 Nov 2015 10:26:38 GMT-08:00

Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose–exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.

Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case Cohort

Sampson, Matthew G. — Tue, 03 Nov 2015 10:26:38 GMT-08:00

To maximize clinical benefits of genetic screening of patients with nephrotic syndrome (NS) to diagnose monogenic causes, reliably distinguishing NS-causing variants from the background of rare, noncausal variants prevalent in all genomes is vital. To determine the prevalence of monogenic NS in a North American case cohort while accounting for background prevalence of genetic variation, we sequenced 21 implicated monogenic NS genes in 312 participants from the Nephrotic Syndrome Study Network and 61 putative controls from the 1000 Genomes Project (1000G). These analyses were extended to available sequence data from approximately 2500 subjects from the 1000G. A typical pathogenicity filter identified causal variants for NS in 4.2% of patients and 5.8% of subjects from the 1000G. We devised a more stringent pathogenicity filtering strategy, reducing background prevalence of causal variants to 1.5%. When applying this stringent filter to patients, prevalence of monogenic NS was 2.9%; of these patients, 67% were pediatric, and 44% had FSGS on biopsy. The rate of complete remission did not associate with monogenic classification. Thus, we identified factors contributing to inaccurate monogenic classification of NS and developed a more accurate variant filtering strategy. The prevalence and clinical correlates of monogenic NS in this sporadically affected cohort differ substantially from those reported for patients referred for genetic analysis. Particularly in unselected, population–based cases, considering putative causal variants in known NS genes from a probabilistic rather than a deterministic perspective may be more precise. We also introduce GeneVetter, a web tool for monogenic assessment of rare disease.

Change in Measured GFR Versus eGFR and CKD Outcomes

Ku, Elaine — Tue, 24 Nov 2015 06:38:53 GMT-08:00

Measured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFRcr) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFRcr. Every 5-ml/min per 1.73 m2 decline in eGFRcr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P<0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P<0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFRcr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.

Ketoanalogue-Supplemented Vegetarian Very Low–Protein Diet and CKD Progression

Garneata, Liliana — Thu, 28 Jan 2016 09:48:38 GMT-08:00

Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue–supplemented vegetarian very low–protein diet (KD) compared with conventional low–protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m2, proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m2. Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m2 but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m2 in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD.

International Comparisons to Assess Effects of Payment and Regulatory Changes in the United States on Anemia Practice in Patients on Hemodialysis: The Dialysis Outcomes and Practice Patterns Study

Fuller, Douglas S. — Wed, 18 Nov 2015 04:57:59 GMT-08:00

For years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in–center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance.

Erratum

American Society of Nephrology — Thu, 30 Jun 2016 10:00:57 GMT-07:00

Tubular Secretion in CKD

Suchy-Dicey, Astrid M. — Fri, 27 Nov 2015 06:38:32 GMT-08:00

Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.

Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during Hemodialysis

Lemoine, Sandrine — Wed, 11 Nov 2015 05:22:25 GMT-08:00

Of the 600–700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous (31P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. 31P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (−30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, βATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.

CKD Prevalence Varies across the European General Population

Brück, Katharina — Wed, 23 Dec 2015 06:57:23 GMT-08:00

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1–5 was defined as eGFR<60 ml/min per 1.73 m2, as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3–5 was defined as eGFR<60 ml/min per 1.73 m2. CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1–5 and CKD stages 3–5 prevalence across European study populations. The adjusted CKD stages 1–5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3–5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

Mitochondria in Kidney Injury: When the Power Plant Fails

Tang, Chengyuan — Thu, 07 Jan 2016 06:07:28 GMT-08:00

Water, Water Everywhere: A New Cause and a New Treatment for Nephrogenic Diabetes Insipidus

Sands, Jeff M. — Mon, 28 Dec 2015 06:30:35 GMT-08:00

Dietary Protein as Kidney Protection: Quality or Quantity?

Goraya, Nimrit — Thu, 28 Jan 2016 09:48:42 GMT-08:00

2-Deoxy-d-Glucose Ameliorates PKD Progression

Chiaravalli, Marco — Tue, 03 Nov 2015 10:26:40 GMT-08:00

Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25–28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of 13C-glucose and conversion to 13C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP–activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45–positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD.

Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet–Induced Kidney Disease

Kuwahara, Shoji — Tue, 03 Nov 2015 10:26:40 GMT-08:00

Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)–induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid–rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid–depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.

Filgrastim–Induced Crescentic Transformation of Recurrent IgG2λ GN

Batal, Ibrahim — Wed, 04 May 2016 05:44:32 GMT-07:00

Proliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony–stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient’s slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony–stimulating factor in exacerbation of preexisting GN.

CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GN

Paust, Hans-Joachim — Tue, 03 Nov 2015 10:26:36 GMT-08:00

Chemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the TH1–associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA–associated crescentic GN and colocalize with CXCR3+ effector T cells. To investigate the functional role of CXCR3+ Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3eGFP-Cre × Cxcr3fl/fl) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming TH1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFNγ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3+ TH1 cells, allowing Treg localization and control of excessive TH1 responses at sites of inflammation.

Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate Model

Yin, Wenqing — Wed, 04 Nov 2015 10:27:54 GMT-08:00

Kidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim-3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models.

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

Hu, Yan — Tue, 03 Nov 2015 10:26:41 GMT-08:00

The close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1+ progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein–coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1+ progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.

Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9

Tsuji, Naoko — Mon, 16 Nov 2015 02:09:36 GMT-08:00

Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the TLR9 pathway and cause kidney injury during sepsis remain unknown. To determine the role of mitochondrial DNA (mtDNA) in TLR9-associated septic AKI, we established a cecal ligation and puncture (CLP) model of sepsis in wild-type (WT) and Tlr9-knockout (Tlr9KO) mice. We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the TLR9 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9KO mice in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9KO mice than in WT mice. Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9KO mice compared with WT mice. Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9KO mice. To elucidate the effects of mtDNA on immune response and kidney injury, we intravenously injected mice with mitochondrial debris (MTD), including substantial amounts of mtDNA. MTD caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and mitochondrial injury, but this effect was attenuated by Tlr9KO. Moreover, MTD-induced renal mitochondrial injury was abolished by DNase pretreatment. These findings suggest that mtDNA activates TLR9 and contributes to cytokine production, splenic apoptosis, and kidney injury during polymicrobial sepsis.

Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi Syndrome

Luciani, Alessandro — Fri, 27 Nov 2015 06:38:33 GMT-08:00

Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS.

Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA Nephropathy

Zhao, Yan-feng — Tue, 29 Mar 2016 09:49:16 GMT-07:00

Risk of Hospital-Acquired Complications in Patients with Chronic Kidney Disease

Bohlouli, Babak — Thu, 12 May 2016 11:21:22 GMT-07:00

The See Kidney Disease Targeted Screening Program for CKD

Galbraith, Lauren E. — Thu, 19 May 2016 06:54:25 GMT-07:00

Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study

Maple-Brown, Louise J. — Wed, 13 Apr 2016 08:04:02 GMT-07:00

Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department

Kimmel, Martin — Tue, 29 Mar 2016 09:49:17 GMT-07:00

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

Leung, Nelson — Fri, 18 Mar 2016 06:47:04 GMT-07:00

Monoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy–associated renal disease is suspected.

Screening Strategies for Unrecognized CKD

Komenda, Paul — Thu, 19 May 2016 06:54:26 GMT-07:00

Beyond APOL1: Genetic Inroads into Understanding Population Disparities in Diabetic Kidney Disease

Skorecki, Karl — Thu, 19 May 2016 06:54:29 GMT-07:00

Integrating a Smartphone–Based Self–Management System into Usual Care of Advanced CKD

Ong, Stephanie W. — Thu, 12 May 2016 11:21:22 GMT-07:00

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps, Elizabeth — Tue, 19 Apr 2016 07:00:30 GMT-07:00

Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

American Society of Nephrology Quiz and Questionnaire 2015: Transplantation

Josephson, Michelle A. — Thu, 25 Feb 2016 07:14:55 GMT-08:00

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of US nephrology fellowship programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special application with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces its educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.

Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy

Sarcina, Cristina — Fri, 29 Apr 2016 06:47:59 GMT-07:00

Predictors of 30-Day Hospital Readmission among Maintenance Hemodialysis Patients: A Hospital’s Perspective

Flythe, Jennifer E. — Thu, 05 May 2016 06:45:49 GMT-07:00

Smartphone Apps: A Patient’s New Best Friend?

Desai, Tejas — Thu, 12 May 2016 11:21:23 GMT-07:00

Bone Parameters and Risk of Hip and Femur Fractures in Patients on Hemodialysis

Fishbane, Steven — Tue, 29 Mar 2016 09:49:18 GMT-07:00

Phosphate Toxicity in CKD: The Killer among Us

Ritter, Cynthia S. — Wed, 10 Feb 2016 06:45:28 GMT-08:00

Maintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last half-century of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.

Survival by Dialysis Modality—Who Cares?

Lee, Martin B. — Thu, 11 Feb 2016 06:38:11 GMT-08:00

In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades.

A Qualitative Study to Explore Patient and Staff Perceptions of Intradialytic Exercise

Thompson, Stephanie — Tue, 29 Mar 2016 09:49:15 GMT-07:00

Strategies for BP Control in Developing Countries and Effects on Kidney Function

Jun, Min — Thu, 19 May 2016 06:54:27 GMT-07:00

Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD

Provenzano, Robert — Tue, 19 Apr 2016 07:00:31 GMT-07:00

Longitudinal Study of Serum Uric Acid, Nutritional Status, and Mortality in Maintenance Hemodialysis Patients

Beberashvili, Ilia — Tue, 29 Mar 2016 09:49:17 GMT-07:00

Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 Signaling

Andrzejewska, Zuzanna — Thu, 08 Oct 2015 10:32:19 GMT-07:00

Cystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin. Lysosomal cystine accumulation leads to crystal formation and functional impairment of multiple organs. Moreover, cystinosis is the most common inherited cause of renal Fanconi syndrome in children. Oral cysteamine therapy delays disease progression by reducing intracellular cystine levels. However, because cysteamine does not correct all complications of cystinosis, including Fanconi syndrome, we hypothesized that cystinosin could have novel roles in addition to transporting cystine out of the lysosome. By coimmunoprecipitation experiments and mass spectrometry, we found cystinosin interacts with almost all components of vacuolar H+-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC. Furthermore, the mammalian target of rapamycin complex 1 (mTORC1) pathway was downregulated in proximal tubular cell lines derived from Ctns−/− mice. Decrease of lysosomal cystine levels by cysteamine did not rescue mTORC1 activation in these cells, suggesting that the downregulation of mTORC1 is due to the absence of cystinosin rather than to the accumulation of cystine. Our results show a dual role for cystinosin as a cystine transporter and as a component of the mTORC1 pathway, and provide an explanation for the appearance of Fanconi syndrome in cystinosis. Furthermore, this study highlights the need to develop new treatments not dependent on lysosomal cystine depletion alone for this devastating disease.

Enhancing Nephrology Career Interest through the ASN Kidney TREKS Program

Maursetter, Laura J. — Tue, 29 Mar 2016 07:00:01 GMT-07:00

The Kidney Tutored Research and Education for Kidney Students (TREKS) Program is a product of the American Society of Nephrology (ASN) Workforce Committee that seeks to connect medical and graduate students to nephrology. This program starts with a weeklong camp–like course introducing participants to renal physiology through classic and modern experiments. Next, each student is matched with a nephrology mentor at his or her home institution to foster a better understanding of a nephrology career. Lastly, the students are encouraged to participate in scholarly activities and attend the ASN Kidney Week. Now in its third year, with a total of 84 participants, survey data suggest early success of the program, with a self–reported 40% increased interest in nephrology fellowship and/or research careers. In addition, students give high ratings to the course components and mentorship pairings. Continued student tracking will be necessary to determine the long–term program effect.

Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation

Huang, Johnny W. — Thu, 08 Oct 2015 10:32:22 GMT-07:00

Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.

Mushroom Clouds for Vitamin D?

Elder, Grahame J. — Thu, 14 Jan 2016 07:16:18 GMT-08:00

Busy Bs

Trachtman, Howard — Mon, 30 Nov 2015 03:23:15 GMT-08:00

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

Djudjaj, Sonja — Fri, 09 Oct 2015 12:18:31 GMT-07:00

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN.

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

Craciun, Florin L. — Thu, 08 Oct 2015 10:32:20 GMT-07:00

CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD.

Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor Construct

Chade, Alejandro R. — Thu, 05 Nov 2015 04:37:26 GMT-08:00

Renovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 μg/kg), a matching concentration of unconjugated VEGF (18.65 μg/kg), ELP alone (100 μg/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP-VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP-VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function.

Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation

Sharmin, Sazia — Thu, 19 Nov 2015 07:06:52 GMT-08:00

Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro. These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm–like structures. Microarray analysis of sorted iPS cell–derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo. Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell–derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell–derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases.

B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome

Colucci, Manuela — Fri, 13 Nov 2015 09:34:22 GMT-08:00

The pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell–depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid–dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age–matched healthy controls (P<0.001). Rituximab induced full depletion of B cells (<1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4+/CD8+ T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8–17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P<0.01) and receiver operator characteristic (P<0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.

Lithium in the Kidney: Friend and Foe?

Alsady, Mohammad — Tue, 17 Nov 2015 06:52:54 GMT-08:00

Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long–term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium–induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.

Alternative Splicing in CKD

Stevens, Megan — Wed, 13 Jan 2016 08:23:55 GMT-08:00

Alternative splicing (AS) has emerged in the postgenomic era as one of the main drivers of proteome diversity, with ≥94% of multiexon genes alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and is a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites, or regulatory sequences. Additionally, compared with the physiologic state, disease often associates with an abnormal proportion of splice isoforms (or novel isoforms), without an apparent driver mutation. It is therefore essential to study how AS is regulated in physiology, how it contributes to pathogenesis, and whether we can manipulate faulty splicing for therapeutic advantage. Although the disease most commonly linked to deregulation of AS in several genes is cancer, many reports detail pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies. A plethora of splice variants have been implicated in CKDs as well. In this review, we describe examples of these CKD-associated splice variants and ideas on how to manipulate them for therapeutic benefit.

Autophagy Induces Prosenescent Changes in Proximal Tubular S3 Segments

Baisantry, Arpita — Tue, 20 Oct 2015 08:37:49 GMT-07:00

Evidence suggests that autophagy promotes the development of cellular senescence. Because cellular senescence contributes to renal aging and promotes the progression from AKI to CKD, we investigated the potential effect of tubular autophagy on senescence induction. Compared with kidneys from control mice, kidneys from mice with conditional deletion of autophagy-related 5 (Atg5) for selective ablation of autophagy in proximal tubular S3 segments (Atg5Δflox/Δflox) presented with significantly less tubular senescence, reduced interstitial fibrosis, and superior renal function 30 days after ischemia/reperfusion injury. To correlate this long-term outcome with differences in the early injury process, kidneys were analyzed 2 hours and 3 days after reperfusion. Notably, compared with kidneys of control mice, Atg5Δflox/Δflox kidneys showed more cell death in outer medullary S3 segments at 2 hours but less tubular damage and inflammation at day 3. These data suggest that the lack of autophagy prevents early survival mechanisms in severely damaged tubular cells. However, if such compromised cells persist, then they may lead to maladaptive repair and proinflammatory changes, thereby facilitating the development of a senescent phenotype and CKD.

A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic Syndrome

Challis, Rachel C. — Wed, 21 Oct 2015 08:11:00 GMT-07:00

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H–related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology–mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.

Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications

Kumar VR, Santhosh — Fri, 13 Nov 2015 09:34:21 GMT-08:00

Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia–induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage–derived circulating PAR2 agonist and mediator of endothelial dysfunction–related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor H

Chauvet, Sophie — Thu, 15 Oct 2015 05:08:05 GMT-07:00

C3 glomerulopathy is a recently described form of CKD. C3GN is a subtype of C3 glomerulopathy characterized by predominant C3 deposits in the glomeruli and is commonly the result of acquired or genetic abnormalities in the alternative pathway (AP) of the complement system. We identified and characterized the first mutation of the C3 gene (p. I734T) in two related individuals diagnosed with C3GN. Immunofluorescence and electron microscopy studies showed C3 deposits in the subendothelial space, associated with unusual deposits located near the complement receptor 1 (CR1)-expressing podocytes. In vitro, this C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1. Both patients had normal plasma C3 levels, and the mutant C3 interacted with factor B comparably to wild-type (WT) C3 to form a C3 convertase. Binding of mutant C3 to factor H was normal, but mutant C3 was less efficiently cleaved by factor I in the presence of factor H, leading to enhanced C3 fragment deposition on glomerular cells. In conclusion, our results reveal that a CR1 functional deficiency is a mechanism of intraglomerular AP dysregulation and could influence the localization of the glomerular C3 deposits.

Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial Repair

Sradnick, Jan — Fri, 09 Oct 2015 12:18:25 GMT-07:00

Endothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concanavalin A model and after ischemia/reperfusion (I/R) injury as well as the potential of extrarenal cells to substitute for injured local EC. Bone marrow transplantation (BMTx), kidney transplantation, or a combination of both were performed before EC injury to allow distinction of extrarenal or BM-derived cells from intrinsic renal cells. During endothelial regeneration, cells expressing markers of endothelial colony-forming cells (ECFCs) were the most abundant EPC subtype in kidneys, but were not detected in blood or spleen. Few cells expressing markers of EC colony-forming units (EC-CFUs) were detected. In BM chimeric mice (C57BL/6 with tandem dimer Tomato-positive [tdT+] BM cells), circulating and splenic EC-CFUs were BM-derived (tdT+), whereas cells positive for ECFC markers in kidneys were not. Indeed, most BM-derived tdT+ cells in injured kidneys were inflammatory cells. Kidneys from C57BL/6 donors transplanted into tdT+ recipients with or without prior BMTx from C57BL/6 mice were negative for BM-derived or extrarenal ECFCs. Overall, extrarenal cells did not substitute for any intrinsic ECs. These results demonstrate that endothelial repair in mouse kidneys with acute endothelial lesions depends exclusively on local mechanisms.

This Month's Highlights

American Society of Nephrology — Tue, 31 May 2016 10:00:54 GMT-07:00

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease

Hwang, Young-Hwan — Fri, 09 Oct 2015 12:18:27 GMT-07:00

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height–adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in–frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in–frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.

Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell Disease

Bartolucci, Pablo — Thu, 19 Nov 2015 07:06:54 GMT-08:00

The earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0–1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1–2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD.

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

Miskulin, Dana C. — Thu, 17 Dec 2015 07:44:12 GMT-08:00

Locally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Shah, Nishant R. — Mon, 12 Oct 2015 12:31:23 GMT-07:00

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all–cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2–1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log–transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all–cause and cardiovascular mortality in patients with dd-ESRD.

Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality Implications

London, Gérard M. — Fri, 16 Oct 2015 06:50:09 GMT-07:00

Aging incurs aortic stiffening and dilation, but these changes are less pronounced in peripheral arteries, resulting in stiffness and geometry gradients influencing progression of the forward and reflected pressure waves. Because premature arterial aging is observed in ESRD, we determined the respective roles of stiffness and aortic geometry gradients in 73 controls and 156 patients on hemodialysis. We measured aortic pulse wave velocity (PWV) and brachial PWV to evaluate the stiffness gradient [(brachial PWV/aortic PWV)0.5] and ascending aortic and aortic bifurcation diameters to assess aortic taper (ascending aortic diameter/aortic bifurcation diameter). The global reflection coefficient was estimated from characteristic impedance and vascular resistance. Cox proportional hazard models were used to determine mortality risk. The age-associated increase in aortic PWV was higher in patients (P<0.001). In controls, aortic ascending and bifurcation diameters increased with age, with an unchanged aortic taper. In patients on hemodialysis, age did not associate with increased ascending aortic diameter but did associate with increased aortic bifurcation diameter and decreased aortic taper, both of which also associated with abdominal aortic calcifications and smaller global reflection coefficient (P<0.001). In patients, multivariate models revealed all-cause and cardiovascular mortality associated with age, aortic PWV, and aortic bifurcation diameter with high specificity and sensitivity. Using stiffness gradient, aortic taper, or global reflection coefficient in the model produced similar results. Thus, whereas aortic stiffness is a known independent predictor of mortality, these results indicate the importance of also evaluating the aortic geometry in patients on hemodialysis.

Androgens Enhance Male Urinary Tract Infection Severity in a New Model

Olson, Patrick D. — Thu, 08 Oct 2015 10:32:17 GMT-07:00

Urinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated.

Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney

Chen, Jianchun — Fri, 09 Oct 2015 12:18:28 GMT-07:00

Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFRptKO) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to high-glucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFR-mediated renal epithelial injury in diabetes.

Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

Xiao, Liangxiang — Fri, 09 Oct 2015 12:18:29 GMT-07:00

AKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing AKI to CKD progression are poorly understood. In this study, we investigated this issue using moderate (20 minutes) and severe (30 minutes) ischemia/reperfusion injury (IRI) in mice. Moderate IRI led to acute kidney failure and transient Wnt/β-catenin activation, which was followed by the restoration of kidney morphology and function. However, severe IRI resulted in sustained and exaggerated Wnt/β-catenin activation, which was accompanied by development of renal fibrotic lesions characterized by interstitial myofibroblast activation and excessive extracellular matrix deposition. To assess the role of sustained Wnt/β-catenin signaling in mediating AKI to CKD progression, we manipulated this signaling by overexpression of Wnt ligand or pharmacologic inhibition of β-catenin. In vivo, overexpression of Wnt1 at 5 days after IRI induced β-catenin activation and accelerated AKI to CKD progression. Conversely, blockade of Wnt/β-catenin by small molecule inhibitor ICG-001 at this point hindered AKI to CKD progression. In vitro, Wnt ligands induced renal interstitial fibroblast activation and promoted fibronectin expression. However, activated fibroblasts readily reverted to a quiescent phenotype after Wnt ligands were removed, suggesting that fibroblast activation requires persistent Wnt signaling. These results indicate that sustained, but not transient, activation of Wnt/β-catenin signaling has a decisive role in driving AKI to CKD progression.

T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment

Dong, Lei — Thu, 08 Oct 2015 10:32:18 GMT-07:00

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment.

Long-Term Effects of Frequent In–Center Hemodialysis

Chertow, Glenn M. — Wed, 14 Oct 2015 06:50:59 GMT-07:00

The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in–center hemodialysis sessions per week for 12 months. As reported previously, frequent in–center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self–reported physical health. Here, we determined the long-term effects of the 12-month frequent in–center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%–90% range, 1.5–5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self–reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post–trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in–center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.

AKI after Transcatheter or Surgical Aortic Valve Replacement

Thongprayoon, Charat — Tue, 20 Oct 2015 08:37:50 GMT-07:00

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.

Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis

Zhou, Xiaoli — Thu, 15 Oct 2015 05:08:06 GMT-07:00

Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate–limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/−) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency–induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/−) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency–induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis.

Celebrating the ASN at 50

Harris, Raymond C. — Tue, 03 May 2016 05:48:10 GMT-07:00

Cathepsin S–Dependent Protease–Activated Receptor-2 Activation: A New Mechanism of Endothelial Dysfunction

Nikolic-Paterson, David J. — Fri, 20 Nov 2015 05:59:48 GMT-08:00

The Ever–Expanding Kidney Repair Shop

Dekel, Benjamin — Mon, 07 Dec 2015 06:42:15 GMT-08:00

HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients

Lim, Wai H. — Thu, 31 Mar 2016 06:46:06 GMT-07:00

HLA-DQ Mismatching: Mounting Evidence for a Role in Kidney Transplant Rejection

Sarabu, Nagaraju — Thu, 31 Mar 2016 06:46:07 GMT-07:00

Apoprotein B/Apoprotein A-1 Ratio and Mortality among Prevalent Dialysis Patients

Sato, Yuji — Mon, 15 Feb 2016 06:59:30 GMT-08:00

Association of Plasminuria with Overhydration in Patients with CKD

Schork, Anja — Tue, 01 Mar 2016 06:43:37 GMT-08:00

Early Requirement for RRT in Children at Presentation in the United Kingdom: Association with Transplantation and Survival

Pruthi, Rishi — Mon, 15 Feb 2016 06:59:31 GMT-08:00

Age and Outcomes Associated with BP in Patients with Incident CKD

Kovesdy, Csaba P. — Thu, 21 Apr 2016 06:58:07 GMT-07:00

Height at First RRT and Mortality in Children

Ku, Elaine — Tue, 01 Mar 2016 06:43:38 GMT-08:00

American Society of Nephrology Quiz and Questionnaire 2015: Glomerular Diseases

Bomback, Andrew S. — Thu, 04 Feb 2016 06:46:00 GMT-08:00

The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.

How to Begin a Quality Improvement Project

Silver, Samuel A. — Fri, 25 Mar 2016 06:43:18 GMT-07:00

Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.

How to Measure and Interpret Quality Improvement Data

McQuillan, Rory Francis — Fri, 25 Mar 2016 06:43:18 GMT-07:00

This article will demonstrate how to conduct a quality improvement project using the change idea generated in “How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem” by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan–Do–Study–Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.

The Continued Quest for Optimal BP Targets in Older Adults with Kidney Disease

Weiss, Jessica W. — Thu, 21 Apr 2016 06:58:07 GMT-07:00

Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4

Ruggenenti, Piero — Mon, 22 Feb 2016 06:48:48 GMT-08:00

In–Center Nutrition Practices of Clinics within a Large Hemodialysis Provider in the United States

Benner, Debbie — Fri, 15 Apr 2016 09:07:57 GMT-07:00

How to Diagnose Solutions to a Quality of Care Problem

Harel, Ziv — Fri, 25 Mar 2016 06:43:16 GMT-07:00

To change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.

Optimal Approach for the Diagnosis of Hemodialysis Catheter–Related Bacteremia

Johns, Tanya S. — Fri, 01 Apr 2016 06:30:13 GMT-07:00

Peanuts or Pretzels? Changing Attitudes about Eating on Hemodialysis

Franch, Harold — Fri, 15 Apr 2016 09:07:56 GMT-07:00

How to Use Quality Improvement Tools in Clinical Practice: A Primer for Nephrologists

Chan, Christopher T. — Fri, 25 Mar 2016 06:43:17 GMT-07:00

Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?

O’Hare, Ann M. — Fri, 15 Apr 2016 09:07:56 GMT-07:00

Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD

Nelson, Delphine R. — Thu, 07 Apr 2016 07:28:43 GMT-07:00

Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial

Torres, Vicente E. — Tue, 23 Feb 2016 07:34:40 GMT-08:00

Nighttime BP in Elderly Individuals with Prediabetes/Diabetes with and without CKD: The HEIJO-KYO Study

Obayashi, Kenji — Thu, 25 Feb 2016 07:14:56 GMT-08:00

Evaluating Approaches for the Diagnosis of Hemodialysis Catheter–Related Bloodstream Infections

Quittnat Pelletier, Friederike — Fri, 01 Apr 2016 06:30:12 GMT-07:00

How to Sustain Change and Support Continuous Quality Improvement

Silver, Samuel A. — Fri, 25 Mar 2016 06:43:17 GMT-07:00

To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

The Provider’s Role in Conservative Care and Advance Care Planning for Patients with ESRD

Obrador, Gregorio T. — Fri, 15 Apr 2016 09:07:54 GMT-07:00

The Obesity Paradox and the Role of Inflammation

Drechsler, Christiane — Mon, 23 Nov 2015 05:54:36 GMT-08:00

Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis

Gan, Poh-Yi — Tue, 15 Sep 2015 04:07:45 GMT-07:00

Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4+ effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV.

Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic Microangiopathy

Vernon, Katherine A. — Tue, 15 Sep 2015 04:07:46 GMT-07:00

The complement–mediated renal diseases C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) strongly associate with inherited and acquired abnormalities in the regulation of the complement alternative pathway (AP). The major negative regulator of the AP is the plasma protein complement factor H (FH). Abnormalities in FH result in uncontrolled activation of C3 through the AP and associate with susceptibility to both C3G and aHUS. Although previously developed FH–deficient animal models have provided important insights into the mechanisms underlying susceptibility to these unique phenotypes, these models do not entirely reproduce the clinical observations. FH is predominantly synthesized in the liver. We generated mice with hepatocyte–specific FH deficiency and showed that these animals have reduced plasma FH levels with secondary reduction in plasma C3. Unlike mice with complete FH deficiency, hepatocyte–specific FH–deficient animals developed neither plasma C5 depletion nor accumulation of C3 along the glomerular basement membrane. In contrast, subtotal FH deficiency associated with mesangial C3 accumulation consistent with C3G. Although there was no evidence of spontaneous thrombotic microangiopathy, the hepatocyte–specific FH–deficient animals developed severe C5–dependent thrombotic microangiopathy after induction of complement activation within the kidney by accelerated serum nephrotoxic nephritis. Taken together, our data indicate that subtotal FH deficiency can give rise to either spontaneous C3G or aHUS after a complement-activating trigger within the kidney and that the latter is C5 dependent.

Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes

Reese, Peter P. — Tue, 15 Sep 2015 04:07:47 GMT-07:00

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m2. In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.

Amniotic Fluid Stem Cells within Chimeric Kidney Rudiments Differentiate to Functional Podocytes after Transplantation into Mature Rat Kidneys

Wilm, Bettina — Thu, 29 Oct 2015 06:08:30 GMT-07:00

CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk Patients

Bottomley, Matthew J. — Thu, 12 Nov 2015 07:53:34 GMT-08:00

Most morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8+ T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57-expressing CD8+ T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8+ T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD57lo) of CD8+ T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction.