799-P: Nephroprotective Effects of a Novel Long-Acting GLP-1/GIP/GCG Triple Agonist, HM15275, in Preclinical Models of Acute and Chronic Kidney Diseases tv pat

Introduction & Objective: Obesity is associated with the risk of chronic kidney disease (CKD). Recently, potential benefits of incretin drugs on cardio- and renal-related outcomes were demonstrated. The aim of this study is to evaluate whether HM15275, which shows a potent anti-obesity effect with optimized GLP-1/GIP/GCG activity balance, also has a renal protective effect. Methods: To investigate therapeutic effect on acute kidney injury, unilateral ureteral obstruction (UUO) mice were administered with HM15275, followed by determining the kidney structure and renal fibrosis. In angiotensin II (Ang II) mice, spontaneously hypertensive rats (SHR), and AMLN mice, renal fibrosis and function were determined after 2 ~ 16 weeks treatment. Human primary podocytes and renal proximal tubular epithelial cells (RPTEC) were used for in vitro mechanistic study. Tirzepatide (TZP) was used as comparative control. Results: UUO-induced increased pro-col1α1 in the kidney was robustly attenuated by HM15275 (-35.3% vs. TZP; p