MR overactivation, implicated in various pathologies including chronic kidney disease (CKD) and type 2 diabetes mellitus, underscores the importance of mineralocorticoid receptor (MR) modulation. Steroidal MR antagonists (MRA) have been pivotal in treating conditions like heart failure, yet their side effects limit their use. Novel non-steroidal MRA, such as finerenone, offer promise with improved safety profiles and demonstrated efficacy in preclinical and clinical settings. Beyond their renal effects, non-steroidal MRAs exhibit systemic impacts, potentially mitigating inflammation, fibrosis, and metabolic dysfunction associated with MR overactivation.
The development of non-steroidal MRA represents a significant advancement, offering a nuanced approach to MR modulation. Clinical trials like FIDELIO-DKD and FIGARO-DKD have demonstrated the efficacy of finerenone in reducing cardiovascular and renal outcomes in patients with CKD and type 2 diabetes. Moreover, ongoing research into MR modulation, including novel compounds and combinations with other agents like SGLT2 inhibitors, suggests a dynamic landscape in the management of cardiorenal and metabolic syndromes.
Reference: Savarese G, Lindberg F, Filippatos G, Butler J, Anker SD. Mineralocorticoid receptor overactivation: targeting systemic impact with non-steroidal mineralocorticoid receptor antagonists. Diabetologia. 2024 Feb;67(2):246-262. doi: 10.1007/s00125-023-06031-1. Epub 2023 Dec 21. PMID: 38127122; PMCID: PMC10789668.
