Fluid Management

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.

Bardoxolone Methyl for Alport Syndrome: Opportunities and Challenges

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

Reproductive Health in Women with Kidney Disease

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

Menstrual Abnormalities and Reproductive Lifespan in Females with CKD

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

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.

Toward Guideline-Directed Medical Therapy in Nephrology

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

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

Effects of Bardoxolone Methyl in Alport Syndrome

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

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.

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

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

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

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

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

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

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.

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

Management of Patients with Kidney Failure and Pericarditis

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

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

McEwan, Phil — Wed, 02 Nov 2022 06:03:30 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.

Community Houses to Increase Access to Home Dialysis

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

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

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

Puttarajappa, Chethan M. — Thu, 27 Oct 2022 06:46:11 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

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

NJain2@uams.edu — Wed, 26 Oct 2022 02:03:07 GMT-07:00

Background. Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stages 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT- aspirin 81 mg/d plus P2Y12 inhibitor). Methods. In a mechanistic clinical trial, we compared platelet activation markers, circulating platelet-leukocyte aggregates, leukocyte composition, and plasma cytokine profile of non-CKD controls (n=26) and CKD outpatients (n=48) with glomerular filtration rate (GFR expressed in ml/min/1.73m2) <30 on 2 weeks of DAPT. Results. Patients with CKD demonstrated reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classical monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine. There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in TNFα levels among a CKD subgroup younger than 55 years, diabetics, had GFR ≥15 or albuminuria ≥1000 mg/g; and, no change in a number of other cytokines. Correlation analysis and minimum spanning trees plot of 45-cytokine panel showed platelet-derived CD40L showed a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1β and PDGF were tightly correlated with other cytokines with IL-1β as the hub cytokine. Conclusion. Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet derived cytokines were one of the central cytokines in CKD. DAPT had multifaceted effects on thromboinflammation suggesting that there are platelet-dependent and platelet-independent inflammation in stages 4 or 5 CKD.

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.

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.

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.

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

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.

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

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.

Obesity in CKD

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

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

How I Treat Focal Segmental Glomerulosclerosis

Liew, Adrian — Tue, 23 Aug 2022 07:06:41 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.