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

Introduction p0.05). In Ang II mice, HM15275 treatment showed significantly less renal dysfunction (BUN, serum creatinine, and uACR). Similarly, elevated levels of renal pro-col1α1 were significantly attenuated by HM15275 (-40.3% vs. TZP; p0.01). In SHRs, urinary albumin excretion (-76.5% vs. TZP; p0.01) and uACR (-72.0% vs. TZP; p0.01) were significantly improved by HM15275 treatment for 16 weeks. Consistently, improvement of gluomerulosclerosis was observed in AMLN mice. In mechanistic study, suppression of stress-induced apoptosis in podocytes and reduced expression of EMT markers in RPTEC well explain how HM15275 could provide renal protection effects in AKI and CKD models. Conclusion: HM15275 improved renal damage and fibrosis more effectively than TZP. Considering the observation in podocytes and RPTEC, HM15275 might have direct nephroprotective effects in addition to the improvement of metabolic abnormalities. Disclosure S. Lee: None. E. Park: None. J. Kim: None. H. Kang: None. J.A. Kim: None. Y. Kim: None. S. Hong: None. S. Bae: None. S. Lee: None. I. Choi: None.