Abstract: TH-PO0624
Circulating Endotrophin Reveals eGFR-Independent Incident CKD Risk Beyond Established Kidney Panel Proteins
Session Information
- CKD: Clinical - Guidelines, Biomarkers, Progression, Procedures, Outcomes, and More
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Audoly, Laurent, Privebio, Inc., Boston, Massachusetts, United States
- Osawa, Itsuki, Columbia University Irving Medical Center, New York, New York, United States
- Becker, Bryan N., TCU Burnett School of Medicine, Fort Worth, Texas, United States
- Scherer, Philipp, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Yoshiji, Satoshi, McGill University, Montreal, Quebec, Canada
Background
Earlier identification of chronic kidney disease (CKD) risk may support monitoring and preventive care. However, eGFR and clinical factors may not capture early renal biologic changes before overt decline in kidney function. Endotrophin, a COL6A3-derived disease-causing protein implicated in fibrosis and inflammation, may reflect renal fibroinflammatory changes prior to diagnosis and add predictive value to proteins in established kidney panels.
Methods
We analyzed 42,416 UK Biobank adults with circulating endotrophin measured and without CKD at baseline. We investigated the association of baseline endotrophin with incident CKD diagnosis using Cox proportional hazards models. Quartile (Q1–Q4) analyses used eGFR adjustment alone, and per-SD analyses were further adjusted for 8 clinical factors (e.g., body mass index, diabetes, hypertension), 3 proteins from the KidneyIntelX Panel, or 18 proteins from the Joslin Kidney Panel. Finally, we performed Reactome pathway analysis using 2,036 endotrophin-correlated proteins.
Results
During median 13.7 years of follow-up, 2,278 participants (5.4%) were diagnosed with incident CKD. In the quartile analysis, Q4 showed higher risk than Q1, with 12-year CKD incidence 6.94% vs 0.40% and eGFR-adjusted HR 3.85 (95% CI 3.20–4.63) (Figure A). Endotrophin remained an independent predictor after adjusting for baseline eGFR (HR per SD 1.53, 95% CI 1.47–1.59, P < 0.001) and after further adjusting for 8 clinical factors (HR 1.37, 95% CI 1.31–1.43, P < 0.001). Endotrophin remained an independent predictor even after adjusting for the proteins from the KidneyIntelX Panel (HR 1.24, 95% CI 1.17–1.31) and those from the Joslin Kidney Panel (HR 1.18, 95% CI 1.09–1.27) (Figure B). Reactome analysis identified 223 enriched pathways supporting a fibroinflammatory proteomic signature, including innate immunity, cytokine signaling, and extracellular matrix organization (all P < 0.001).
Conclusion
Circulating eGFR-independent endotrophin may capture a fibroinflammatory risk signal for incident CKD and add predictive value beyond the established kidney panel proteins.
Figure. Baseline endotrophin stratifies the risk of incident CKD (A) and remains an independent predictor after adjustment for established kidney protein panels (B).
Funding
- Commercial Support – Privebio, Inc.