Abstract-Levels

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, nineteen associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biologic pathways.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.

Context Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type 1 DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy.

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