Urinary Connective Tissue Growth Factor Excretion Correlates With Clinical Markers of Renal Disease in a Large Population of Type 1 Diabetic Patients With Diabetic Nephropathy

Abstract

OBJECTIVE—Levels of connective tissue growth factor (CTGF; CCN-2) in plasma are increased in various fibrotic disorders, including diabetic nephropathy. Recently, several articles have reported a strong increase of urinary CTGF excretion (U-CTGF) in patients with diabetic nephropathy. However, these studies addressed too small a number of patients to allow general conclusions to be drawn. Therefore, we evaluated U-CTGF in a large cross-sectional study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Subjects were 318 type 1 diabetic patients and 29 normoglycemic control subjects. U-CTGF was measured by sandwich enzyme-linked immunosorbent assay. Groups were compared by Kruskal-Wallis and Mann-Whitney analysis. The relation between U-CTGF and markers of diabetic nephropathy was determined by regression analysis. RESULTS—U-CTGF in patients with diabetic nephropathy (n = 89, median 155 pmol/24 h [interquartile range 96–258]) was significantly higher than in microalbuminuric (n = 79, 100 [65–78]) and normoalbuminuric (n = 150, 85 [48–127]) patients and control subjects (n = 29, 100 [78–114]). U-CTGF correlated with urinary albumin excretion (UAE) (R = 0.31) and glomerular filtration rate (R = −0.38) in patients with diabetic nephropathy. A standardized increase in U-CTGF was associated with diabetic nephropathy (odds ratio 2.3 [95% CI 1.7–3.1]), which was comparable with the odds ratios for diabetic nephropathy of increased HbA1c (2.0 [1.5–2.7]), and blood pressure (2.0 [1.5–2.6]). CONCLUSIONS—This is the first large cross-sectional study addressing U-CTGF in human type 1 diabetes. The observed association of U-CTGF with UAE and glomerular filtration rate might reflect a role of CTGF as progression promoter in diabetic nephropathy.