Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function–related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10−8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function–related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD.
To our knowledge, this study provides the first estimates of human in vivo GSCs. Our model explains why tubular proteinuria of Fanconi syndrome includes proteins of mass of albumin and above as well as low-molecular-weight proteins, and further characterizes the endocytic pathway(s) believed defective in these syndromes. High urinary concentrations of potentially bioactive hormones such as PTH, insulin, IGF-1 and the chemokine monocyte chemoattractant protein-1 (MCP-1), were found; their presence in tubular fluid may contribute to the hypercalciuria, interstitial fibrosis, and the progressive renal failure of Fanconi syndromes.
Remote preconditioning reduces urinary biomarkers of renal injury in patients undergoing elective EVAR. This small pilot trial was unable to detect an effect on clinical endpoints; further trials are warranted.
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