Kidney Week

Abstract: TH-PO0631

Endotrophin Provides Prognostic Information on Fibrotic Activity Beyond Traditional Risk Factors and Kidney Injury Biomarkers

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

• Groen, Solveig Skovlund, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark

Solveig Skovlund Groen, MSc, PhD

• McDonnell, Thomas, Donal O'Donoghue Renal Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom

Thomas McDonnell, MBChB

• Kalra, Philip A., Donal O'Donoghue Renal Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom

Philip A. Kalra, MD, MBChB

• Genovese, Federica, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark

Federica Genovese, PhD

• Taal, Maarten W., Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom

Maarten W. Taal, MD, MBChB

Background

Fibrosis is a key driver of chronic kidney disease (CKD) progression. Endotrophin, a pro-fibrotic fragment of type VI collagen, may capture fibrotic activity beyond established inflammatory and kidney injury biomarkers. We evaluated circulating endotrophin in the NURTuRE-CKD cohort and benchmarked it against established biomarkers.

Methods

Endotrophin was measured using nordicEndotrophin™ ELISA in baseline serum samples (n=1517) from CKD patients from NURTuRE-CKD. For biomarker benchmarking, in matched samples TNFR1, KIM-1, NGAL and suPAR were quantified in plasma, GDF15 in serum, and MMP-9, KIM-1, C3M (nordicC3M™) in urine samples corrected for urinary creatinine. Endpoints were a combined kidney endpoint (CKE: ≥50% decline in eGFR, eGFR ≤15 ml/min/1.73m² or initiation of kidney replacement therapy), eGFR slope and all-cause mortality. Joint biomarker models including endotrophin and comparator biomarkers were used to assess independent prognostic value. Biomarkers were log₂-transformed and scaled to their interquartile range (IQR). Models were fully adjusted for age, sex, race, income, diabetes, hypertension, BMI, ACEI/ARB use, cardiovascular disease, smoking, baseline eGFR, and baseline log₂-uACR.

Results

Median follow-up was 3.9 years (IQR 3.0–4.47), and 610 developed CKE. Per IQR increase in log₂-endotrophin, the cumulative incidence of CKE increased by 73% (sHR 1.73, p<0.0001), corresponding to a 13% higher cumulative incidence of CKE per 20% increase in endotrophin after accounting for competing risk. Higher endotrophin was also associated with faster annual eGFR decline (β −0.57 mL/min/1.73m²/year, p=0.006) and increased all-cause mortality risk (HR 1.68, p<0.0001). In joint biomarker model, endotrophin showed the strongest independent association with CKE among all evaluated biomarkers, with 59% higher cumulative incidence of CKE (sHR 1.59, p<0.0001). For eGFR slope, urinary KIM-1 was associated with the fastest decline (β −0.57 mL/min/1.73m²/year per IQR increase, p=0.001).

Conclusion

Endotrophin was independently associated with several kidney endpoints and provides prognostic information about active fibrotic ongoing processes not reflected by traditional risk factors and injury/inflammation markers. Endotrophin may be a promising candidate for fibrosis endotyping and in identifying patients likely to benefit from antifibrotic therapies.