AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Survodutide Improves Renal Function in Obesity-Related Kidney Injury in Uninephrectomized Mice
By Zhang HF, Xiang JY, Zhang ZY et al.
Background: Survodutide, a dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist, exhibits potent anti-obesity effects, but its impact on obesity-related chronic kidney disease (CKD) is not incompletely understood. Methods: Male C57BL/6NRj mice underwent unilateral nephrectomy (UniNx) or sham surgery. UniNx mice were fed a normal diet (ND) and received placebo or high-fat high-salt diet (HFHS). HFHS mice received placebo or survodutide (7.5 or 15 nmol/kg/day, s.c.subcutaneous) for 6 weeks. Body weight, blood pressure, intraperitoneal glucose tolerance (IPGTT), and glomerular filtration rate (GFR) were assessed. Renal injury was evaluated by albuminuria, proteinuria, and histology. Results: HFHS-fed UniNx mice developed obesity, hypertension, and renal dysfunction. Survodutide reduced body weight (~20%) to 26.6 ± 0.1 g (7.5 nmol/kg/day) and 25.0 ± 0.2 g (15 nmol/kg/day) versus 31.3 ± 0.2 g (vehicleplacebo; p < 0.0001). Blood pressure was markedly reduced in both doses of survodutide (SBPsystolic/Ddiastolic BPblood pressure: 116/85 and 114/83 mmHg vs. 162/125 mmHg (vehicleplacebo); p < 0.001). Glucose tolerance improved significantly (IPGTT AUC area under the curve reduced from 1344 ± 117 (vehicleplacebo) to 814 ± 70 and 892 ± 68 mmol·min/L; p < 0.01 in the survodutide dose of 7.5 and 15 nmol/kg, respectively). GFR decline (198 ± 6 μL/min) in HFHS vs ND mice (317 ± 21 μL/min ) was partially reversed in both doses of survodutide (281 ± 27 and 282 ± 23); p < 0.05). Albuminuria and proteinuria were reduced, accompanied by decreased tubulointerstitial injury, collagen deposition, and mesangial expansion. Conclusions: Survodutide improves metabolic parameters, blood pressure, renal function, and structural kidney injury in obesity-related CKD, supporting therapeutic benefits beyond weight loss.