Association Between Urinary Type IV Collagen Level and Deterioration of Renal Function in Type 2 Diabetic Patients Without Overt Proteinuria

OBJECTIVE Cross-sectional studies have reported increased levels of urinary type IV collagen in diabetic patients with progression of diabetic nephropathy. The aim of this study was to determine the role of urinary type IV collagen in predicting development and progression of early diabetic nephropathy and deterioration of renal function in a longitudinal study. RESEARCH DESIGN AND METHODS Japanese patients with type 2 diabetes (n = 254, 185 with normoalbuminuria and 69 with microalbuminuria) were enrolled in an observational follow-up study. The associations of urinary type IV collagen with progression of nephropathy and annual decline in estimated glomerular filtration rate (eGFR) were evaluated. RESULTS At baseline, urinary type IV collagen levels were higher in patients with microalbuminuria than in those with normoalbuminuria and correlated with urinary beta(2)-microglobulin (beta = 0.57, P < 0.001), diastolic blood pressure (beta = 0.15, P < 0.01), eGFR (beta = 0.15, P < 0.01), and urinary albumin excretion rate (beta = 0.13, P = 0.01) as determined by multivariate regression analysis. In the follow-up study (median duration 8 years), urinary type IV collagen level at baseline was not associated with progression to a higher stage of diabetic nephropathy. However, the level of urinary type IV collagen inversely correlated with the annual decline in eGFR (gamma = -0.34, P < 0.001). Multivariate regression analysis identified urinary type IV collagen, eGFR at baseline, and hypertension as factors associated with the annual decline in eGFR. CONCLUSIONS Our results indicate that high urinary excretion of type IV collagen is associated with deterioration of renal function in type 2 diabetic patients without overt proteinuria.