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Diabetic kidney disease (DKD) is characterized by glomerular hypertrophy, hyperfiltration, inflammation, and the onset of albuminuria, together with a progressive reduction in glomerular filtration rate. This progression is further accompanied by tubulointerstitial inflammation and fibrosis. Factors such as genetic predisposition, epigenetic modifications, metabolic derangements, hemodynamic alterations, inflammation, and inappropriate renin-angiotensin-aldosterone system (RAAS) activity contribute to the onset and progression of DKD. In this context, decades of work have focused on glycemic and blood pressure reduction strategies, especially targeting the RAAS to slow disease progression. Although much of the work has focused on targeting angiotensin II, emerging data support that the mineralocorticoid receptor (MR) is integral in the development and progression of DKD. Molecular mechanisms linked to the underlying pathophysiological changes derived from MR activation include vascular endothelial and epithelial cell responses to oxidative stress and inflammation. These responses lead to alterations in the microcirculatory environment, the abnormal release of extracellular vesicles, gut dysbiosis, epithelial-mesenchymal transition, and kidney fibrosis. Herein, we present recent experimental and clinical evidence on the MR in DKD onset and progress along with new MR-based strategies for the treatment and prevention of DKD. <\/jats:p>","DOI":"10.1152\/ajprenal.00135.2024","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T18:00:31Z","timestamp":1721325631000},"page":"F519-F531","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["The mineralocorticoid receptor in diabetic kidney disease"],"prefix":"10.1152","volume":"327","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-5925","authenticated-orcid":false,"given":"Guanghong","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, United States"},{"name":"Research Service, Harry S. 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