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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 [48-1271) patients and control subjects (n = 29, 100 [78-1141). 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 HbA[sub 1c] (2.0 [1.5-2.7]), and blood pressure (2.0 [1.5-2.61). 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. [ABSTRACT FROM AUTHOR]

Reduction of urinary connective tissue growth factor by Losartan in type 1 patients with diabetic nephropathy.Background.Connective tissue growth factor (CTGF) is an important profibrotic cytokine implicated in development of diabetic glomerulosclerosis. Urinary CTGF is reported to be significantly increased in patients with diabetic nephropathy. The present study aimed to investigate the short- and long term effects of angiotensin II receptor blockade by Losartan on urinary CTGF levels in hypertensive type 1 diabetic patients with diabetic nephropathy.Methods.Seventy-one hypertensive type 1 diabetic patients with diabetic nephropathy were included in the study. After a washout period of 4 weeks, the patients received Losartan 50 mg, 100 mg, and 150 mg once daily in treatment periods each lasting 2 months. Thereafter, patients were followed prospectively during treatment with Losartan 100 mg o.d. with a total mean follow-up time of 36 months. At baseline, after 2, 4, and 6 months and then biannually, urinary and plasma CTGF levels[enzyme linked immunosorbent assay (ELISA) fibroGen], albuminuria (Turbidimetry), glomerular filtration rate (GFR)[51-creatinine ethylenediaminetetraacetic acid (51Cr-EDTA plasma clearance)] and 24 hours blood pressure (TM2420)) were determined.Results.Baseline levels of urinary and plasma CTGF were 7076 (5708 to 8770) ng/24 hours[geometric mean (95% CI)] and 12.7 (7.3) ng/mL[mean (SD)], respectively. Albuminuria, GFR, and arterial blood pressure at baseline were 1152 (937 to 1416) mg/24 hours, 88 (24) mL/min/1.73 m2, and 153/80 (17/9) mm Hg, respectively. Losartan significantly reduced urinary CTGF by 21% (9 to 31) (95% CI) initially (P<0.05 vs. baseline), with no further reduction after increasing dose. The sustained reduction in urinary CTGF was 22% (12 to 32) (P<0.05 vs. baseline). Rate of decline in GFR during the study was 3.2 (−1.6 to 15.9) mL/min/year[median (range)]. Reduction in urinary CTGF was correlated with a lower rate of decline in GFR (r= 0.23,P= 0.05). Plasma CTGF remained unchanged throughout the study.Conclusion.Our 3-year study demonstrates that Losartan persistently reduces urinary CTGF excretion, which is associated with a slower rate of decline in GFR. [ABSTRACT FROM AUTHOR]