{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:50:34Z","timestamp":1793994634749,"version":"4.8.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,10,25]],"date-time":"2020-10-25T00:00:00Z","timestamp":1603584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This review covers the last 80\u2009years of remarkable progress in the development of mineralocorticoid receptor (MR) antagonists (MRAs) from synthesis of the first mineralocorticoid to trials of nonsteroidal MRAs. The MR is a nuclear receptor expressed in many tissues\/cell types including the kidney, heart, immune cells, and fibroblasts. The MR directly affects target gene expression\u2014primarily fluid, electrolyte and haemodynamic homeostasis, and also, but less appreciated, tissue remodelling. Pathophysiological overactivation of the MR leads to inflammation and fibrosis in cardiorenal disease. We discuss the mechanisms of action of nonsteroidal MRAs and how they differ from steroidal MRAs. Nonsteroidal MRAs have demonstrated important differences in their distribution, binding mode to the MR and subsequent gene expression. For example, the novel nonsteroidal MRA finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys. Compared with eplerenone, equinatriuretic doses of finerenone show more potent anti-inflammatory and anti-fibrotic effects on the kidney in rodent models. Overall, nonsteroidal MRAs appear to demonstrate a better benefit\u2013risk ratio than steroidal MRAs, where risk is measured as the propensity for hyperkalaemia. Among patients with Type 2 diabetes, several Phase II studies of finerenone show promising results, supporting benefits on the heart and kidneys. Furthermore, finerenone significantly reduced the combined primary endpoint (chronic kidney disease progression, kidney failure, or kidney death) vs. placebo when added to the standard of care in a large Phase III trial.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaa736","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T15:44:33Z","timestamp":1598975073000},"page":"152-161","source":"Crossref","is-referenced-by-count":623,"title":["Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine and VA Medical Center , 1481 West 10th Street, 111N Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-7528","authenticated-orcid":false,"given":"Peter","family":"Kolkhof","sequence":"additional","affiliation":[{"name":"R&D Preclinical Research Cardiovascular , Bayer AG, Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-1267","authenticated-orcid":false,"given":"George","family":"Bakris","sequence":"additional","affiliation":[{"name":"American Society of Hypertension's Comprehensive Hypertension Center at the University of Chicago Medicine , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School , Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-6446","authenticated-orcid":false,"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School , Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-3645","authenticated-orcid":false,"given":"Takashi","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Laboratory Medicine, Kanazawa University , Kanazawa, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique, University Henri Poincar\u00e9 , Nancy, 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