Abstract: TH-PO1117
Biomarkers of Collagen Turnover and Fibrotic Activity Are Prognostic for Kidney Outcomes in CKD: Data from CRIC and NURTuRE-CKD
Session Information
- CKD: Therapies, Innovations, and Insights
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Groen, Solveig Skovlund, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark
- Gupta, Jayanta, Florida Gulf Coast University Marieb College of Health & Human Services, Fort Myers, Florida, United States
- McDonnell, Thomas, Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Srivastava, Anvesha, The George Washington University, Washington, District of Columbia, United States
- Kalra, Philip A., Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, England, United Kingdom
- Genovese, Federica, Nordic Bioscience, Herlev, Capital Region of Denmark, Denmark
- Taal, Maarten W., University of Nottingham, Nottingham, England, United Kingdom
- Raj, Dominic S., The George Washington University, Washington, District of Columbia, United States
Background
Fibrosis is a central pathogenic process in CKD progression, and biomarkers reflecting this process may offer prognostic value. We evaluated two biomarkers: PRO-C6, a pro-fibrotic signaling fragment of type VI collagen, and uC3M, a degradation fragment of type III collagen in two large well-characterized, prospective, multicenter non-dialysis CKD cohorts.
Methods
PRO-C6 was measured using nordicPRO-C6™ ELISA in baseline plasma (CRIC, n=962) and serum (NURTuRE-CKD, n= 2867). uC3M was measured using nordicuC3M™ ELISA in baseline urine (CRIC, n=986; NURTuRE-CKD, n=2193), normalized to urine creatinine. Linear regression, adjusted for sex, age, BMI, ethnicity, smoking, ACE-I/ARB use, income, cardiovascular disease, diabetes, hypertension, baseline eGFR, and uACR (log2), assessed associations between each biomarker (log2) and annual eGFR slope. Cox regression, adjusting for same covariates, evaluated associations with a composite outcome: ≥50% eGFR decline or onset of ESKD (eGFR<15 ml/min/1.73 m2). Discrimination was assessed using AUC and Uno’s C-statistic, comparing models with biomarkers added to a base clinical model.
Results
PRO-C6 was negatively, and uC3M was positively, associated with annual eGFR slope in CRIC (PRO-C6: β: -0.81, p<0.0001, uC3M: β: 0.27, p=0.002) and NURTuRE-CKD (PRO-C6: β: -1.10, p<0.0001, uC3M: β: 0.65, p=0.002). A doubling of PRO-C6 increased, while a doubling of uC3M decreased, the risk of composite outcome in CRIC (PRO-C6: HR: 1.82, p<0.0001; uC3M: HR: 0.87, p=0.006) and NURTuRE-CKD (PRO-C6: HR: 2.00, p<0.0001; uC3M: HR: 0.84, p=0.014). Participants with higher levels of PRO-C6 had higher risk for composite outcome in CRIC (HR: 1.82, p<0.0001) and NURTuRE-CKD (HR: 2.12, p<0.0001). Addition of PRO-C6 to base clinical model improved AUC from 0.841 to 0.847 (p=0.016) in CRIC, and from 0.775 to 0.792 (p<0.0001) in NURTuRE-CKD.
Conclusion
In both CRIC and NURTuRE-CKD, levels of PRO-C6 and uC3M were associated with increased risk of kidney outcomes, supporting their use as non-invasive biomarkers of fibrosis in CKD.
| Biomarker | CKD cohort | Annual mean eGFR slope β-coefficient (95% CI) | p-value | Composite outcome Hazard ratio (95% Cl) | p-value |
| PRO-C6 | CRIC | Log2 -0.81 (-1.14 to -0.48) Tertiles T1: Reference T2: -0.49 (-0.93 to -0.05) T3: -1.08 (-1.60 to -0.56) | <0.0001 0.03 <0.0001 | Log2 1.82 (1.48 to 2.23) Tertiles T1: Reference T2: 1.42 (1.01 to 1.98) T3: 1.82 (1.25 to 2.65) | <0.0001 0.04 <0.0001 |
| NURTuRE-CKD | Log2 -1.10 (-1.59 to -0.62) Tertiles T1: Reference T2: -0.36 (-0.98 to -0.26) T3: -0.81 (-1.52 to -0.10) | <0.0001 0.3 0.03 | Log2 2.00 (1.72 to 2.32) Tertiles T1: Reference T2: 1.34 (1.06 to 1.70) T3: 2.12 (1.65 to 2.72) | <0.0001 0.01 <0.0001 | |
| uC3M | CRIC | Log2 0.27 (0.10 to 0.44) Tertiles T1: Reference T2: 0.42 (0.01 to 0.83) T3: 0.59 (0.16 to 1.02) | 0.002 0.04 0.007 | Log2 0.87 (0.79 to 0.96) Tertiles T1: Reference T2: 0.74 (0.58 to 0.94) T3: 0.71 (0.55 to 0.93) | 0.006 0.01 0.01 |
| NURTuRE-CKD | Log2 0.65 (0.24 to 1.06) Tertiles T1: Reference T2: 0.31 (-0.30 to 0.91) T3: 0.91 (0.22 to 1.60) | 0.002 0.3 0.01 | Log2 0.84 (0.73 to 0.97) Tertiles T1: Reference T2: 0.85 (0.70 to 1.03) T3: 0.86 (0.68 to 1.09) | 0.014 0.09 0.2 |
Funding
- Other NIH Support