Kidney Week

Abstract: FR-PO0846

Circulating Propeptide of Type VI Collagen (PRO-C6) Provides Independent Prognostic Information and Identifies Fibrotic Disease Activity Even in Low-Risk IgAN Patients

Session Information

• Glomerular Diseases: Practice and New Concepts Shaping Modern Care
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

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

PRO-C6 is a pro-fibrotic signaling fragment of type VI collagen which is central in the interstitial matrix remodeling during IgA Nephropathy (IgAN) progression. We evaluated PRO-C6 in urine and serum from IgAN patients recruited through the NURTuRE-CKD cohort.

Methods

PRO-C6 was measured by nordicPRO-C6™ ELISA in matched baseline serum and urine samples from 183 IgAN patients and 86 healthy controls. uPRO-C6 was normalized to urine creatinine. Spearman correlations assessed relationships with clinical parameters. Cox regression with adjustments for age, baseline eGFR, and log₂-uACR were conducted for each biomarker (log₂ and IQR-standardized) with a combined kidney endpoint (CKE) defined as ≥50% eGFR decline, ESKD [eGFR <15 ml/min/1.73 m²], or kidney replacement therapy. Patients were further stratified by uACR and eGFR categories and compared with healthy controls.

Results

IgAN patients had a median age of 50 (IQR 42.2-61) years and were 68% male, while healthy controls had median age of 55.5 (43.5-67.8) years and were 37.2% male. sPRO-C6 correlated weakly with uPRO-C6 (r=0.28, p=0.0007). uPRO-C6 correlated moderately with uACR (r=0.41, p<0.0001), whereas sPRO-C6 did not. uPRO-C6 showed weak inverse correlation with eGFR (r=-0.26, p=0.001) while sPRO-C6 showed a strong inverse correlation (r=-0.65, p=<0.0001). Higher sPRO-C6 (Q1-Q3:12.3-21.6 ng/mL) was independently associated with increased risk of CKE (HR 2.59, Cl 1.45-4.61, p=0.001), corresponding to a 17% higher risk of CKE per 10% increase of sPRO-C6. uPRO-C6 (Q1-Q3:1.5-4.7 ng/mL) was not significantly associated with CKE. In stratified analysis, IgAN patients in all uACR groups including the lowest uACR group (≤0.3 g/g) had higher sPRO-C6 levels compared to healthy controls (p<0.0001). uPRO-C6 was elevated in the highest uACR category (p=0.009) and lower in the lowest uACR category (p=0.004) compared with healthy controls. sPRO-C6 was elevated in early CKD (G1-G2) compared to healthy (p<0.0001), with gradual increase to G4 (p<0.001).

Conclusion

Circulating PRO-C6 is associated with risk of kidney disease progression in IgAN patients, independently of age, eGFR, and uACR. These results support the mechanistic importance of fibrotic activity in IgAN progression and suggest that PRO-C6 in serum may provide additional information on progression risk even in patients with low risk.