Journal of the American Society of Nephrology : JASN

BACKGROUND: Large increases in glomerular protein filtration induce major changes in body homeostasis and increase risk of kidney functional decline and cardiovascular disease. We investigated how elevated protein exposure modifies the landscape of tubular function along the entire nephron, to understand the cellular changes that mediate these important clinical phenomena. METHODS: We conducted single nuclei RNA sequencing, functional intravital imaging, and antibody staining to spatially map transport processes along the mouse kidney tubule...

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The number of individuals with acute kidney injury receiving outpatient dialysis (AKI-D) is increasing. At present, based on limited data, approximately one third of individuals with AKI-D who receive outpatient dialysis after hospital discharge survive and regain sufficient kidney function to discontinue dialysis. Data to inform dialysis management strategies that promote kidney function recovery and processes of care among individuals with AKI-D receiving outpatient dialysis are lacking. In this article, we detail current trends in the incidence, risk factors, clinical outcomes, proposed management, and health policy landscape for individuals with AKI-D receiving outpatient dialysis and identify areas for further research...

In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney TREKS (Tutored Research and Education for Kidney Scholars) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a one-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness...

BACKGROUND: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes. METHODS: We present an integrated analysis of 4,091 proteins and 630 metabolites in the Chronic Renal Insufficiency Cohort Study (N=1,708; average follow-up for kidney failure [KF], 9.5 years, with 537 events). Proteins and metabolites were integrated using an unsupervised clustering method and we assessed associations between clusters and CKD progression and kidney failure using Cox proportional hazards models...

BACKGROUND: The link between the histology of kidney transplant rejection, especially Antibody-mediated rejection, T cell-mediated rejection and Mixed rejection, and the types of infiltrating immune cells is currently not well charted. Cost and technical complexity of single cell analysis hinder large scale studies of the relationship between cell infiltrate profiles and histological heterogeneity. METHODS: In this cross-sectional study, we assessed the composition of nine intragraft immune cell types by using a validated kidney transplant-specific signature matrix for deconvolution of bulk transcriptomics in three different kidney transplant biopsy datasets (N=403, N=224, N=282)...

BACKGROUND: Hyperglycaemia influences the development of glomerular endothelial cell damage and nowhere is this more evident than in the progression of diabetic kidney disease (DKD). While the Set7 lysine methyltransferase is a known hyperglycaemic sensor, its role in endothelial cell function in the context of DKD remains poorly understood. METHODS: Single-cell transcriptomics was used to investigate Set7 regulation in a mouse model of DKD, followed by validation of findings using pharmacological and shRNA inhibition of Set7...

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BACKGROUND: Accumulated evidence demonstrates that long non-coding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood due to the lack of a reference map of lncRNA transcriptome in various cell types. METHODS: In this study, we employed a targeted single-cell RNA sequencing (scRNA-seq) method to enrich and characterize lncRNAs in individual cells...

BACKGROUND: Observational studies have found an association between proton pump inhibitor (PPI) use and worsening kidney function. It is unclear whether these associations are causal.We conducted post-hoc analyses to determine the effect of pantoprazole on kidney function using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, a 17,598 participant randomized trial comparing pantoprazole (8,791) to placebo (8,807). METHODS: The primary outcome was the rate of change of estimated glomerular filtration rate (eGFR)...

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BACKGROUND: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes kidney injury and tubulointerstitial fibrosis. Little is known about prospective associations between TMAO and kidney outcomes, especially incident CKD. We hypothesized that higher plasma TMAO levels would be associated with higher risk of incident CKD and greater rate of kidney function decline. METHODS: We included 10,564 participants from two community-based, prospective cohorts with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Rab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. Additionally, sea urchin Rab35 regulates actin organization and is required for gastrulation. In mice, loss of Rab35 in the CNS disrupts hippocampal development and neuronal organization. Outside of the CNS, the functions of mammalian Rab35 in vivo are unknown...

BACKGROUND: The synthetic tetra-peptide SS-31 shows promise in alleviating mitochondrial dysfunction associated with common diseases. However, the precise pharmacological basis of its mitoprotective effects remains unknown. METHODS: To uncover the biological targets of SS-31, we performed a genome-scale CRISPR screen in HK-2 cells, a cell culture model where SS-31 mitigates cisplatin-associated cell death and mitochondrial dysfunction. The identified hit candidate gene was functionally validated using knockout cell lines, siRNA mediated downregulation, and tubular epithelial specific conditional knockout mice...