Serum and Urine Markers of Collagen Type VI Formation (Pro-C6) and Type III Degradation (C3M) Reflect Renal Function in Type 1 Diabetes

Background Progression of diabetic kidney disease is associated with renal fibrogenesis and associated with increased extracellular matrix remodeling and release of collagen fragments in urine in progressive renal disease. We evaluated associations between kidney function and a marker of collagen type VI formation (Pro-C6) and a marker of collagen type III degradation (C3M) in type 1 diabetes. Methods Serum and urinary levels of Pro-C6 and C3M were measured with ELISA in 668 patients with type 1 diabetes. Kidney function was evaluated as eGFR (CKD-EPI) and urinary albumin excretion rate (UAER). We applied unadjusted and adjusted linear regression analyses.Adjustment included age, sex, LDL cholesterol, smoking, HbA1c, systolic blood pressure, UAER (in analyses of eGFR) and eGFR (in analyses of UAER). To adjust for urine output levels, the urinary markers were normalized for urinary creatinine. Results Of the 668 patients, 368 (55%) were male, mean±SD age was 54.6±12.6 years and eGFR 81.6±25.5 ml/min/1.73m2. Median (IQR) UAER was 17 (8-65) mg/g. Both higher serum and urinary levels of Pro-C6 were associated with lower eGFR (unadjusted: p<0.001; adjusted: p<0.001) and higher UAER (unadjusted: p<0.001; adjusted: p<0.001). Lower urinary levels of C3M were associated with lower eGFR (unadjusted: p<0.001; adjusted: p<0.001) and higher UAER in the unadjusted model (p<0.001), but significance was lost after adjustment (p=0.43). Higher serum levels of C3M were associated with lower eGFR (unadjusted: p<0.001; adjusted: p=0.001) and higher UAER (unadjusted: p<0.001; adjusted: p=0.007). Conclusion In type 1 diabetes, higher serum and urine levels of the collagen type VI formation marker Pro-C6 were associated with poorer kidney function. Moreover, higher serum levels and lower urine levels of the collagen type III degradation marker C3M were related to poorer kidney function. Longitudinal data are needed to clarify the predictive role of these markers.