The mineralocorticoid receptor in chronic kidney disease

Chronic kidney disease (CKD) is a major public health concern, affecting approximately 10% of the population worldwide. CKD of glomerular or tubular origin leads to the activation of stress mechanisms, including the renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR) activation. Over the last two decades, blockade of the MR has arisen as a potential therapeutic approach against various forms of kidney disease. In this review, we summarize the experimental studies that have shown a protective effect of MR antagonists (MRAs) in nondiabetic and diabetic CKD animal models. Moreover, we review the main clinical trials that have shown the clinical application of MRAs to reduce albuminuria and, importantly, to slow CKD progression. Recent evidence from the FIDELIO trial showed that the MRA finerenone can reduce hard kidney outcomes when added to the standard of care in CKD associated with type 2 diabetes. Finally, we discuss the effects of MRAs relative to those of SGLT2 inhibitors, as well as the potential benefit of combination therapy to maximize organ protection.

Automated summary

Chronic kidney disease is a major public health concern globally, with MR antagonists emerging as a potential therapeutic approach against various forms of kidney disease. Experimental and clinical studies have shown the protective effects of MRAs in reducing albuminuria and slowing disease progression. Recent evidence also suggests that MRAs can reduce hard kidney outcomes, particularly in CKD associated with type 2 diabetes, highlighting their potential benefit in maximizing organ protection through combination therapy.