Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb;67(2):246-262.
doi: 10.1007/s00125-023-06031-1. Epub 2023 Dec 21.

Mineralocorticoid receptor overactivation: targeting systemic impact with non-steroidal mineralocorticoid receptor antagonists

Gianluigi Savarese  1   2 , Felix Lindberg  3 , Gerasimos Filippatos  4 , Javed Butler  5   6 , Stefan D Anker  7   8
Affiliations
Review

Mineralocorticoid receptor overactivation: targeting systemic impact with non-steroidal mineralocorticoid receptor antagonists

Gianluigi Savarese et al. Diabetologia. 2024 Feb.

Abstract

The overactivation of the mineralocorticoid receptor (MR) promotes pathophysiological processes related to multiple physiological systems, including the heart, vasculature, adipose tissue and kidneys. The inhibition of the MR with classical MR antagonists (MRA) has successfully improved outcomes most evidently in heart failure. However, real and perceived risk of side effects and limited tolerability associated with classical MRA have represented barriers to implementing MRA in settings where they have been already proven efficacious (heart failure with reduced ejection fraction) and studying their potential role in settings where they might be beneficial but where risk of safety events is perceived to be higher (renal disease). Novel non-steroidal MRA have distinct properties that might translate into favourable clinical effects and better safety profiles as compared with MRA currently used in clinical practice. Randomised trials have shown benefits of non-steroidal MRA in a range of clinical contexts, including diabetic kidney disease, hypertension and heart failure. This review provides an overview of the literature on the systemic impact of MR overactivation across organ systems. Moreover, we summarise the evidence from preclinical studies and clinical trials that have set the stage for a potential new paradigm of MR antagonism.

Keywords: Eplerenone; Finerenone; Mineralocorticoid receptor; Mineralocorticoid receptor antagonists; Review; Spironolactone.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Role of MR overactivation in cardiorenal disease. ROS, reactive oxygen species. This figure is available as part of a downloadable slideset
Fig. 2
Fig. 2
Distinct characteristics and mechanisms of finerenone vs classical steroidal MRA. CV, cardiovascular; DOCA, deoxycorticosterone acetate; HF, heart failure; MI, myocardial infarction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; T2DM, type 2 diabetes mellitus. This figure is available as part of a downloadable slideset
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Shibata S, Nagase M, Yoshida S, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14(12):1370–1376. doi: 10.1038/nm.1879. - DOI - PubMed
    1. Ingelsson E, Pencina MJ, Tofler GH, et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study. Circulation. 2007;116(9):984–992. doi: 10.1161/CIRCULATIONAHA.107.708537. - DOI - PubMed
    1. Beygui F, Collet JP, Benoliel JJ, et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation. 2006;114(24):2604–2610. doi: 10.1161/CIRCULATIONAHA.106.634626. - DOI - PubMed
    1. Güder G, Bauersachs J, Frantz S, et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation. 2007;115(13):1754–1761. doi: 10.1161/CIRCULATIONAHA.106.653964. - DOI - PubMed
    1. Agarwal R, Kolkhof P, Bakris G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J. 2021;42(2):152–161. doi: 10.1093/eurheartj/ehaa736. - DOI - PMC - PubMed

MeSH terms

-