{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:01Z","timestamp":1786480261654,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Reneo Pharmaceuticals","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2023,3]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n \n A peroxisome proliferator-activated receptor\n \u03b4<\/jats:italic>\n agonist, REN001, ameliorates kidney dysfunction in a mouse model of Alport syndrome.\n <\/jats:p>\n <\/jats:list-item>\n \n REN001 suppresses glomerular injury and renal fibrosis.<\/jats:p>\n <\/jats:list-item>\n \n REN001 decreases the levels of inflammation- and fibrosis-related proteins.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Alport syndrome is a genetic kidney disease caused by mutation in any of the\n COL4A3<\/jats:italic>\n ,\n COL4A4<\/jats:italic>\n , or\n COL4A5<\/jats:italic>\n genes encoding the type IV collagen\n \u03b1<\/jats:italic>\n 3,\n \u03b1<\/jats:italic>\n 4, and\n \u03b1<\/jats:italic>\n 5 chains. Defects of type IV collagen\n \u03b1<\/jats:italic>\n 3\n \u03b1<\/jats:italic>\n 4\n \u03b1<\/jats:italic>\n 5 cause glomerular basement membrane abnormalities and lead to defects in glomerular filtration and ESKD. Treatment with angiotensin-converting enzyme inhibitors (ACEis) dramatically slows disease progression but does not stop progression to renal failure. Therefore, novel therapeutic options with different modes of action from ACEis are needed. Peroxisome proliferator-activated receptor (PPAR)\n \u03b4<\/jats:italic>\n agonists have shown renoprotective effects in several acute kidney injury mouse models. In this study, we investigated the effects of a potent and selective PPAR\n \u03b4<\/jats:italic>\n agonist, REN001 (formerly HPP593), in a mouse model of Alport syndrome.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We administered REN001 from the early stages to the late stages of disease by once daily intraperitoneal injections.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n REN001 treatment halved proteinuria at the late stages of disease in\n Col4a3<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice. BUN levels were also decreased, and histological and molecular analyses showed that REN001 ameliorated renal inflammation and fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These results indicate that REN001 slows kidney disease progression in Alport mice. REN001 has a different mechanism of action from ACEis, so we, therefore, hypothesize that combining the two treatments may show additive effects to attenuate renal injury and slow progression to renal failure.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0006662022","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T01:38:06Z","timestamp":1669772286000},"page":"341-348","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["PPAR\u03b4 Agonism Ameliorates Renal Fibrosis in an Alport Syndrome Mouse Model"],"prefix":"10.34067","volume":"4","author":[{"given":"Kohei","family":"Omachi","sequence":"first","affiliation":[{"name":"Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"O'Carroll","sequence":"additional","affiliation":[{"name":"Acadia Pharmaceuticals Inc., San 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