{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:11:00Z","timestamp":1790655060663,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Boehringer Ingelheim"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vicadrostat, a selective aldosterone synthase inhibitor, reduced albuminuria with concurrent renin\u2013angiotensin system inhibition and empagliflozin, suggesting additive efficacy for chronic kidney disease (CKD) treatment. Specific urinary extracellular vesicle microRNAs (uEV miRNAs) may reflect key mechanisms of kidney injury. We investigated how vicadrostat alone or with empagliflozin affected uEV miRNA expression in study participants. Small RNA sequencing was conducted on uEV miRNAs from 435 participants with CKD who completed 14 weeks treatment in the phase II trial of vicadrostat given with or without empagliflozin. Differentially expressed uEV miRNAs in participants with \u226530% UACR (urine albumin\u2013creatinine ratio) reduction treated with 10 or 20 mg vicadrostat were pooled and evaluated with or without empagliflozin. Changes in miRNA-142-5p correlated significantly with changes in UACR in participants treated with vicadrostat alone, whereas changes in expression of eight additional uEV miRNAs (miR-192-5p, miR-194-5p, miR-6882-5p, miR-27a-5p, miR-381-3p, miR-192-3p, miR-513a-5p, and miR-199b-3p) correlated with \u226530% UACR improvements in patients treated with vicadrostat plus empagliflozin. Cellular deconvolution revealed that these miRNAs were expressed in various kidney cell types. Vicadrostat plus empagliflozin altered uEV miRNAs involved in immunomodulatory and fibrotic pathways irrespective of participant diabetes status. Regulation of miRNAs may provide insights into synergistic mechanisms of vicadrostat and empagliflozin in CKD treatment.<\/jats:p>","DOI":"10.3390\/ijms262210810","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:14:45Z","timestamp":1762506885000},"page":"10810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urine Extracellular Vesicle miRNA Changes Induced by Vicadrostat with\/Without Empagliflozin in Patients with Chronic Kidney Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-3134","authenticated-orcid":false,"given":"Denis","family":"Delic","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach, Germany"},{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, 68167 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-576X","authenticated-orcid":false,"given":"Isabella","family":"Gashaw","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, 55216 Ingelheim am Rhein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Duran-Fernandez","sequence":"additional","affiliation":[{"name":"Staburo GmbH, 81549 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Cronin","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle J.","family":"Hauske","sequence":"additional","affiliation":[{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, 68167 Heidelberg, Germany"},{"name":"Boehringer Ingelheim International GmbH, 55216 Ingelheim am Rhein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, 2730 Herlev, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-0103","authenticated-orcid":false,"given":"Katherine R.","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Providence Inland Northwest Health, Spokane, WA 99201, USA"},{"name":"Nephrology Division, Kidney Research Institute, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.kint.2018.04.011","article-title":"Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016","volume":"94","author":"Xie","year":"2018","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Deng, L., Guo, S., Liu, Y., Zhou, Y., Liu, Y., Zheng, X., Yu, X., and Shuai, P. 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