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However, research has uncovered the deleterious consequences of overactivation of the MR. It has been implicated in chronic kidney disease (CKD) via its strong association with glomerulosclerosis, interstitial fibrosis, proteinuria, and decline in glomerular filtration rate, as well as in cardiovascular diseases through mechanisms such as excessive extracellular matrix accumulation, oxidative stress, haemodynamic changes, and sustained inflammation. As such, efforts have poured into developing therapeutic agents to inhibit the detrimental effects of MR overactivation. This narrative review describes the background to elucidating the role of MR overactivation in CKD associated with diabetes, followed by an overview of the clinical development history of MR antagonists (MRAs), initially steroidal, followed by agents with non\u2010steroidal structure. Clinical trials have demonstrated antiproteinuric effects of both MRA classes; however, only the non\u2010steroidal class has shown reductions in major adverse kidney events, with finerenone being the most widely studied. Both MRA classes also benefit heart failure and hypertension, common comorbidities in CKD, though steroidal MRAs have shown greater antihypertensive effects as well as greater risk for hyperkalaemia. This review also highlights guideline recommendations that have been developed to incorporate the latest clinical evidence, along with practical ways to manage hyperkalaemia with MRA use.<\/jats:p>","DOI":"10.1111\/dom.70587","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:50:35Z","timestamp":1773125435000},"page":"3568-3581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mineralocorticoid receptor antagonists: Efficacy and safety in chronic kidney disease"],"prefix":"10.1111","volume":"28","author":[{"given":"Amy K.","family":"Mottl","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension University of North Carolina School of Medicine  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2343-7099","authenticated-orcid":false,"given":"Kamlesh","family":"Khunti","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre, Leicester Diabetes Research Centre University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4055-5233","authenticated-orcid":false,"given":"Chantal","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology University Hospitals Leuven\u2014KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"issue":"6","key":"e_1_2_10_2_1","first-page":"515","article-title":"Production of nephrosclerosis by overdosage with desoxycorticosterone acetate","volume":"47","author":"Selye H","year":"1942","journal-title":"Can Med Assoc J"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/joe\u201016\u20100600"},{"issue":"2","key":"e_1_2_10_4_1","first-page":"88","article-title":"Malignant hypertension produced by treatment with desoxycorticosterone acetate and sodium chloride","volume":"49","author":"Selye H","year":"1943","journal-title":"Can Med Assoc J"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.126.3281.1016"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.126.3281.1015"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo\u201064\u20102\u2010299"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa736"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010023\u201006031\u20101"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201003263\u20105"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010024\u201000820\u20106"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010023\u201006015\u20101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010024\u201008021\u2010z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25\u2010S011"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad192"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21358"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.694758"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2022.04.016"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2016_76"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15747"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14\u20101296"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1879"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000528783"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2003.10.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001184"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1476029"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.7472"},{"key":"e_1_2_10_29_1","unstructured":"Bayer AG.Kerendia\u2122 (finerenone) granted expanded indication in the EU for broad range of patients with chronic kidney disease and type 2 diabetes.2023. 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