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.
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.


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 HbA(1c) (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.
Nguyen
Tri Q
TQ
Department of Pathology, University Medical Center Utrecht, H04.312, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands. t.q.nguyen@lab.azu.nl
Tarnow
Lise
L
Andersen
Steen
S
Hovind
Peter
P
Parving
Hans-Henrik
HH
Goldschmeding
Roel
R
van Nieuwenhoven
Frans A
FA
D000328:Adult; D015415:Biomarkers / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D017874:Immediate-Early Proteins / Q000652:urine*; D036341:Intercellular Signaling Peptides and Proteins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis
D015415:Biomarkers; D001786:Blood Glucose; D055513:Connective Tissue Growth Factor; D006442:Glycated Hemoglobin; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C526317:CCN2 protein, human