Abstract: SA-PO0409
Circulating Endotrophin Is Associated with Incident Kidney Disease, with Differential Effects Across Obesity Phenotypes in the General Population
Session Information
- CKM: Clinical - Epidemiology and Outcomes
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Genovese, Federica, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark
- Laursen, Clara Fia Gøricke, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark
- Nizamoglu, Mehmet, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
- Evans, David Robert, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
- Karsdal, Morten Asser, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark
- Bakker, Stephan J.L., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
- De Borst, Martin H., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands
Background
Endotrophin, a pro-fibrotic signalling peptide derived from collagen type VI, has emerged as a biomarker of chronic kidney disease (CKD) progression. In this study we investigated its association with incident CKD in the general population and explored the influence of metabolic disease in this association.
Methods
Serum endotrophin was measured in 3,677 participants to the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort using the nordicEndotrophin™ immunoassay. The participants did not have prevalent CKD (defined as reaching an eGFR<60 mL/min/1.73 m2 or uACR>30 mg/g) at baseline. Cox proportional hazards models were used to assess the association between doubling of endotrophin and incident CKD. Secondary analyses were performed across obesity phenotypes defined by BMI categories (<25 (lean), 25–30 (overweight), ≥30 (obese) kg/m2) and relative fat mass (RFM) tertiles (low, medium, high). The primary model was adjusted for age, sex, diabetes, hypertension, and BMI (or RFM in analyses stratified by BMI categories).
Results
Mean ± SD age at baseline was 53.6 ± 12.2 years, 52 % were female, BMI was 26.7 ± 4.3 kg/m2, RFM was 32.1 ± 7.3 %, and eGFR was 91.6 ± 17.3 mL/min/1.73m2..33.4% of participants had hypertension and 3.4% had diabetes. Over a median follow-up of 7.4 years [IQR 7.1–7.8], 550 individuals developed CKD. A doubling of circulating endotrophin was independently associated with an increased risk of incident CKD (HR 1.76, 95% CI 1.32–2.34; p<0.001). When stratified by BMI category, endotrophin was associated with incident CKD in obese (HR 2.16, 95% CI 1.27–3.69; p=0.005) and overweight individuals (HR 1.63, 95% CI 1.05–2.52; p=0.03), but not in lean individuals (HR 1.45, 95% CI 0.86–2.46; p=0.2). Similarly, the association was strongest in the high RFM group (HR 3.31, 95% CI 1.99–5.47; p<0.001), compared with the medium (HR 1.30, 95% CI 0.84–2.03; p=0.2) and low RFM groups (HR 1.21, 95% CI 0.69–2.14; p=0.5). A significant interaction was observed between endotrophin and RFM status (P-interaction = 0.01) but not BMI.
Conclusion
Higher circulating endotrophin is independently associated with an increased risk of incident CKD in the general population. The association is stronger in individuals with higher adiposity, suggesting a heightened prognostic potential for endotrophin in metabolically unhealthy individuals.