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Conference poster
Published 10-2025
Journal of the American Society of Nephrology, 36, 10S, 10.1681/ASN.2025mxhmsgvr
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.