Intrarenal Hemodynamic Mechanisms of Kidney Protection by Nonsteroidal Mineralocorticoid Receptor Antagonists

Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), especially finerenone, have shown significant cardiorenal benefits in patients with chronic kidney disease (CKD). Clinical trials consistently report reductions in albuminuria and improved renal outcomes; however, the specific intrarenal hemodynamic mechanisms remain partially understood. nsMRAs lower albuminuria, a critical surrogate marker for CKD progression, with early reductions contributing significantly to renal benefits. These agents produce mild natriuretic effects by inhibiting aldosterone-mediated sodium reabsorption in the distal nephron, resulting in a slight reduction in extracellular volume. Additionally, nsMRAs may impact glomerular hemodynamics by mitigating aldosterone-induced constriction of the efferent arterioles and restoring tubuloglomerular feedback, while also modulating connecting tubule glomerular feedback. Collectively, these effects may contribute to lowering intraglomerular pressure and attenuating glomerular hyperfiltration. However, current evidence does not definitively show that nsMRAs are superior to steroidal mineralocorticoid receptor antagonists in correcting hyperfiltration. Their clinical benefits seem to arise from enhanced safety, tolerability, and sustained therapeutic use. This narrative review synthesizes existing clinical and experimental evidence on the intrarenal hemodynamic effects of nsMRAs, emphasizing their roles in sodium handling, natriuresis, and regulation of intraglomerular pressure.