journal of the american society of nephrology

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)...

BACKGROUND: There have been scarce epidemiological data on the relationship between inflammatory bowel disease and the incidence of Immunoglobulin A (IgA) nephropathy. In this study, we assessed whether inflammatory bowel disease was associated with a higher risk of developing IgA nephropathy using a large-scale epidemiological cohort. METHODS: We retrospectively analyzed 4,311,393 adults enrolled in the JMDC Claims Database (previously known as the Japan Medical Data Center database), a nationwide epidemiological database in Japan...

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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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