1728-P: Large-Scale Proteomic Discovery of Prognostic and Treatment-Responsive CKD Biomarkers in SELECT

Introduction and Objective: Biomarkers that predict chronic kidney disease (CKD) progression, cardiovascular (CV) complications, and treatment responses in patients (pts) with obesity are needed for precision medicine. We aimed to use proteomics from SELECT to identify prognostic (associated with CKD outcomes) and predictive (associated with differential treatment responses) biomarkers. Methods: SomaScan v4.1 profiled 6300 proteins in 30,000 serum samples from ~11,000 pts treated with semaglutide (sema) 2.4 mg or placebo at baseline, weeks 20 and 104. Adjusted linear models tested protein associations with eGFR decline, UACR change, a composite nephropathy outcome, and treatment response (11.2% of the CKD subpopulation). Results: Prognostic analyses revealed 350 proteins, many linked to fibroinflammatory pathways (KIM-1, TNFR1, COL18A1, MMP7, NPPB), were associated with eGFR decline, UACR change, or a composite nephropathy outcome (adjusted p0.05). Treatment effect analyses identified ~1400 sema-modulated proteins; 15 overlapped with known CKD candidate biomarkers, including 3 that were prognostic (ANGPT2, NPPB, COL18A1) (Figure). Conclusion: Integrated clinical and proteomics data identified potential prognostic cardio-kidney biomarkers, major disease-relevant pathways, and some sema-modulated response biomarkers. Planned validation and assay/risk-model development may inform future trial designs and personalized therapy. Disclosure P. Bjornstad: Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. H.M. Colhoun: Research Support; Current; Diabetes UK, IQVIA Inc., Sanofi, JDRF, Chief Scientist Office. Research Support; Ended; Medical Research Council (UKRI). Other - Personal payment for consultancy (ENDED);Research support (ongoing); Current; Sanofi. Other - Advisory board member (ongoing); Support for attendance at meetings /conferences and travel; Current; Novo Nordisk. Other - Advisory panel member (ongoing);Stockholder (up to January 2025- ENDED); Current; Bayer AG. Other - Stockholder (ongoing);Institutional payment for consultancy (ongoing); Current; Roche Pharmaceuticals. K. Tuttle: Consultant; Ended; Alnylam Pharmaceuticals, Inc. Consultant; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Novo Nordisk, Lilly, ProKidney. Consultant; Ended; Roche Diabetes Care. Research Support; Ended; Travere. S. Kahn: Advisory Panel; Current; AltPep, Amgen Inc., Congruence Therapeutics, Eli Lilly and Company, General Medicines, Kayothera, Merck Current; Novo Nordisk A/S. K.B. Hessellund: Employee; Current; Novo Nordisk A/S. K. Sulek: Employee; Current; Novo Nordisk A/S. N. Rathor: None. T.N. Wistisen: Employee; Current; Novo Nordisk. F. Palluzzi: Employee; Current; Novo Nordisk A/S. M. Triana Iglesias: Employee; Current; Novo Nordisk. T. Idorn: Employee; Ended; Novo Nordisk A/S. Other - Full-time employee of stealth mode biotech from 1-Jan-2026; Current; Stealth mode biotech. L. Bjerre Knudsen: Employee; Current; Novo Nordisk. V. Das: Employee; Current; Novo Nordisk A/S.