Non-steroidal mineralocorticoid receptor antagonists in non-diabetic kidney disease: a narrative review of mechanisms and clinical advances.

Authors

Fei Luo, Jingjia Hu, Hongliang Fang, Xianfa Li, Caifeng Zhu, Ziyang Bao

Published in

BMC nephrology. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Significant advances have been made in elucidating the role of non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) in non-diabetic kidney disease (NDKD). As a key downstream effector of the renin-angiotensin system (RAS), pathological overactivation of the mineralocorticoid receptor (MR) amplifies inflammatory and fibrotic signaling, thereby contributing to proteinuria, podocyte injury, and progressive damage to both the glomerular and tubulointerstitial compartments. Mechanistic studies suggest that ns-MRAs exert multi-level protective effects by targeting the inflammation-fibrosis axis, including preservation of podocyte structure and function, attenuation of acute kidney injury-to-chronic kidney disease transition, improvement of endothelial dysfunction, and suppression of cardiac and renal fibrosis. Clinically, the phase III FIND-CKD trial has provided direct randomized evidence that finerenone slows estimated glomerular filtration rate (eGFR) decline in adults with proteinuric CKD without diabetes, while a prespecified exploratory analysis further supports its potential relevance in glomerular diseases. Real-world studies in IgA nephropathy and membranous nephropathy also suggest antiproteinuric effects when finerenone is added to renin-angiotensin system inhibition. Moreover, co-administration with sodium-glucose cotransporter 2 (SGLT2) inhibitors may confer complementary antiproteinuric effects, although hyperkalemia remains an important safety consideration requiring appropriate monitoring. Collectively, current randomized and observational evidence supports consideration of ns-MRAs in selected patients with proteinuric NDKD, while highlighting the need for subtype-specific interpretation, serum potassium monitoring, and precision-stratified treatment strategies.

PMID:
42469710
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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