Finerenon verbetert albuminurie via MR-TRPC-signalering bij diabetische nierziekte

BACKGROUND:Recent studies have confirmed the protective effects of nonsteroidal MR (mineralocorticoid receptor) antagonists in diabetic kidney disease. However, the physiological mechanisms underlying their albuminuria-reducing effects remain incompletely defined. We hypothesized that inhibition of the MR could protect podocytes by limiting excessive calcium influx via TRPC (transient receptor potential canonical) 5, thereby reducing albuminuria.METHODS:We evaluated the effects of the nonsteroidal MR antagonist finerenone on albuminuria, podocyte morphology, and glomerular function in diabetic mice. Reactive oxygen species generation and single-nephron glomerular filtration rate were analyzed using in vivo imaging. Cultured podocytes were used to assess MR-TRPC5 signaling through measurements of Sgk1 (serum- and glucocorticoid-regulated kinase 1) and TRPC5 expression, intracellular calcium, and actin cytoskeletal organization.RESULTS:Finerenone significantly reduced albuminuria, amelio