{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:00:57Z","timestamp":1791910857501,"version":"4.3.4"},"reference-count":144,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perception of the role of the aldosterone\/mineralocorticoid receptor (MR) ensemble has been extended from a previously renal epithelial-centered focus on sodium and volume homeostasis to an understanding of their role as systemic modulators of reactive oxygen species, inflammation, and fibrosis. Steroidal MR antagonists (MRAs) are included in treatment paradigms for resistant hypertension and heart failure with reduced ejection fraction, while more recently, the nonsteroidal MRA finerenone was shown to reduce renal and cardiovascular outcomes in two large phase III trials (FIDELIO-DKD and FIGARO-DKD) in patients with chronic kidney disease and type 2 diabetes, respectively. Here, we provide an overview of the pathophysiologic role of MR overactivation and preclinical evidence with the nonsteroidal MRA finerenone in a range of different disease models with respect to major components of the aggregate mode of action, including interfering with reactive oxygen species generation, inflammation, fibrosis, and hypertrophy. We describe a time-dependent effect of these mechanistic components and the potential modification of major clinical parameters, as well as the impact on clinical renal and cardiovascular outcomes as observed in FIDELIO-DKD and FIGARO-DKD. Finally, we provide an outlook on potential future clinical indications and ongoing clinical studies with finerenone, including a combination study with a sodium\u2013glucose cotransporter-2 inhibitor.<\/jats:p>","DOI":"10.3390\/ijms23169243","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T21:23:56Z","timestamp":1660771436000},"page":"9243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Nonsteroidal Mineralocorticoid Receptor Antagonism by Finerenone\u2014Translational Aspects and Clinical Perspectives across Multiple Organ Systems"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-7528","authenticated-orcid":false,"given":"Peter","family":"Kolkhof","sequence":"first","affiliation":[{"name":"Cardiology Precision Medicines, Research & Early Development, Bayer AG, Aprather Weg 18a, 42113 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lawatscheck","sequence":"additional","affiliation":[{"name":"Clinical Development, Bayer AG, M\u00fcller Stra\u00dfe 178, Building P300, 13342 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-0332","authenticated-orcid":false,"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Mikras Asias 75, 115 27 Athina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-1267","authenticated-orcid":false,"given":"George L.","family":"Bakris","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1111\/bph.15747","article-title":"Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease","volume":"179","author":"Kintscher","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/pr.115.011106","article-title":"Emerging roles of the mineralocorticoid receptor in pathology: Toward new paradigms in clinical pharmacology","volume":"68","author":"Jaisser","year":"2016","journal-title":"Pharmacol. 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