Serum and urinary type IV collagen concentrations in the assessment of diabetic microangiopathy

We investigated the role of measurement of serum and urinary type IV collagen (IV-C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV-C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated.