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To gain mechanistic insights, the current study aimed to establish a murine model of hypertensive CKD that shows cardio\u2010renal protection by sotagliflozin. Since protection by SGLT2 inhibitors can be diabetes\u2010independent, a nondiabetic murine model of subtotal nephrectomy with angiotensin II infusion\u2010facilitated hypertension was followed for 7\u2009weeks. The model showed 40% lower GFR, doubling in plasma FGF23, 50\u2009mmHg higher systolic blood pressure (SBP), 100\u2010fold increased albuminuria, and robust signs of kidney injury, inflammation, and fibrosis versus sham controls, associated with a 30% larger left cardiac ventricle and wall thickness and upregulation of markers of cardiac overload and fibrosis. Sotagliflozin, initiated 1\u2009week after the last surgery, showed target\u2010engagement evidenced by glucosuria, 9\u2009mmHg lower SBP, temporal reduction in body weight and GFR, and 30% higher plasma GLP1. Sotagliflozin, however, did not improve markers of kidney injury, inflammation, fibrosis, albuminuria, and plasma FGF23, or signs of cardiac overload, fibrosis, or impaired function. Limited sotagliflozin responsiveness may relate to short treatment time, limited metabolic benefits in nondiabetic setting and\/or the model's dominant angiotensin II\u2010driven effects\/hypertension.<\/jats:p>","DOI":"10.14814\/phy2.70217","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T14:50:37Z","timestamp":1743346237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of sotagliflozin on kidney and cardiac outcome in a hypertensive model of subtotal nephrectomy in male mice"],"prefix":"10.14814","volume":"13","author":[{"given":"Helen","family":"Goodluck","sequence":"first","affiliation":[{"name":"Division of Nephrology &amp; Hypertension, Department of Medicine University of California San Diego, and VA San Diego Healthcare System  San Diego California 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