Common Charge-Shift Mutation Glu65Lys in K+ Channel β1-Subunit KCNMB1: Pleiotropic Consequences for Glomerular Filtration Rate and Progressive Renal Disease

摘要

BackgroundGlomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca²⁺ influx, which is controlled by the regulatory β1-subunit (KCNMB1) of large-conductance heteromeric K⁺ (‘BK’) channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline.