{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:41:10Z","timestamp":1785508870178,"version":"3.56.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>Background: Diabetic kidney disease (DKD) is a common disorder with multiple serious clinical implications, including an increased risk of end-stage kidney disease (ESKD), cardiovascular complications, heart failure, onset or worsening of hypertension, and premature death. Patients with DKD frequently require dialysis or kidney transplantation to manage their ESKD. Summary: Upregulation of the renin-angiotensin-aldosterone system is an important contributor to kidney disease progression, as highlighted by the results of trials evaluating angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with albuminuria. Increasing evidence suggests the existence of a multidirectional network that involves aldosterone, the mineralocorticoid receptor (MR), and the Ras-related C3 botulinum toxin substrate 1 (Rac1) as driving forces in the generation of reactive oxygen species and oxidative stress-induced injury in the initiation of interstitial nephritis and eventual fibrosis in chronic kidney disease and DKD. The MR is a key element of this triangle, as highlighted by the beneficial effect of MR antagonists in preventing or reducing aldosterone- or Rac1-related effects in basic science studies, and the improved patient outcomes observed in clinical studies. Key Messages: Aldosterone can promote kidney disease in diabetes via the MR and via MR-independent actions through Rac1. However, the MR remains a key element of this triangle, with clinical data supporting the use of MR antagonists in delaying the progression of kidney disease in diabetes. <\/jats:p>","DOI":"10.1159\/000528783","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T22:01:17Z","timestamp":1674252077000},"page":"50-61","source":"Crossref","is-referenced-by-count":36,"title":["Mineralocorticoid Receptor-Associated Mechanisms in Diabetic Kidney Disease and Clinical Significance of Mineralocorticoid Receptor Antagonists"],"prefix":"10.1159","volume":"54","author":[{"given":"Christian W.","family":"Mende","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Samarakoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2023,1,20]]},"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/ajn\/article-pdf\/54\/1-2\/50\/3957194\/000528783.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/ajn\/article-pdf\/54\/1-2\/50\/3957194\/000528783.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:06:39Z","timestamp":1745420799000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000528783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":0,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2023,5,30]]},"published-print":{"date-parts":[[2023,5,23]]}},"URL":"https:\/\/doi.org\/10.1159\/000528783","archive":["Portico"],"relation":{},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]}}}