Finerenone in Reducing Proteinuria: Clinical Effects, Underlying Mechanisms, and Associated Cardiorenal Protection.

Abstract

Proteinuria remains a cardinal surrogate of renal injury and cardiorenal risk, However, residual albuminuria is commonly observed after the treatment with renin-angiotensin-aldosterone system (RAAS) blockade or sodium-glucose cotransporter-2 inhibitors (SGLT2i). The non-steroidal, selective mineralocorticoid receptor antagonist(MRA) finerenone has recently been demonstrated to possess albuminuria-lowering and organ-protective effects, Nonetheless, its precise mechanisms of action and the full scope of its benefits within combination drug regimens require further elucidation. This review comprehensively synthesizes the clinical evidence for finerenone as an antiproteinuric agent in chronic kidney disease (CKD) and summarizes its potential mechanisms of action. Finerenone acts as an inverse agonist by binding to the mineralocorticoid receptor, thereby concurrently suppressing both genomic and non-genomic aldosterone signaling. This action inhibits pro-fibrotic, pro-inflammatory, and hemodynamic pathways that collectively contribute to damage of the glomerular filtration barrier, ultimately leading to the observed alleviation of proteinuria. Clinical studies have confirmed that finerenone reduces albuminuria, slows the progression of kidney failure, and decreases the risk of cardiovascular events, with a lower incidence of hyperkalemia compared to steroidal MRAs. Regarding combination therapies, the renal protective effects of finerenone are enhanced when used concomitantly with either RAAS blockers or SGLT2 inhibitors. However, its clinical benefits in non-diabetic CKD populations remain to be substantiated by large-scale studies. Furthermore, the mechanisms underlying its intrarenal hemodynamic protection require further elucidation, and the optimal combination strategies and the underlying mechanisms for the potential benefits of such regimens await validation through large-scale, randomized controlled trials.