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Diabetes Care 29:83-88, 2006
DOI: 10.2337/diacare.29.01.06.dc05-1670
© 2006 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

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

Tri Q. Nguyen, MD1, Lise Tarnow, MD, DMSC2, Steen Andersen, MD, DMSC2, Peter Hovind, MD, DMSC2, Hans-Henrik Parving, MD, DMSC2, Roel Goldschmeding, MD, PHD1 and Frans A. van Nieuwenhoven, PHD1

1 Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
2 Steno Diabetes Center, Gentofte, Denmark

Address correspondence and reprint requests to Tri Q. Nguyen, University Medical Center Utrecht, Department of Pathology, H04.312, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. E-mail: t.q.nguyen{at}lab.azu.nl

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.

Abbreviations: ARB, angiotensin II receptor blocker • CTGF, connective tissue growth factor • GFR, glomerular filtration rate • UAE, urinary albumin excretion • U-CTGF, urinary CTGF excretion


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Copyright © 2006 by the American Diabetes Association.