October 31, 2004
American Society of Nephrology (ASN) Renal Week 2004, St. Louis, Missouri
Abstract SU-PO176
Poster: Clinical Nephrology / Diabetes Mellitus: Epidemiology/Treatment

Connective Tissue Growth Factor (CTGF) Plasma Levels Correlate with Plasma Creatinine Levels in Patients with Type I Diabetes Mellitus (DM). P. Roestenberg, L. Tarnow, L. Wieten, N. Oliver, W. Usinger, H.H. Parving, R. Goldschmeding, F.A. van Nieuwenhoven. Pathology, UMCU, Utrecht, Netherlands; Steno Diabetes Center, Gentofte, Denmark; Fibrogen Inc., South San Francisco, CA.

CTGF is a 36-38 kDa protein strongly upregulated in fibrotic disorders including diabetic nephropathy (DN). Plasma CTGF level and urinary CTGF excretion is increased in both human and experimental DN. Furthermore, plasma CTGF levels of type 1 diabetic patients were correlated with albuminuria and creatinine clearance. The aim of the present study was to investigate the possible association of plasma CTGF levels with markers of DN in a larger cross sectional study of patients with type 1 DM.

387 patients with type 1 DM were included in the study. 199 patients had DN, which was clinically defined as urinary albumin excretion rate (UAER) > 300 mg/24h in at least two of three consecutive 24h urine collections, presence of retinopathy and no evidence of other kidney disease. 188 DM patients with normoalbuminuria (NA), who were matched for sex, age and duration of DM, were included as controls.

Plasma CTGF levels were determined by sandwich ELISA. Stepwise regression analysis was used to analyse the possible correlation between plasma CTGF levels and relevant patient characteristics. Plasma CTGF levels were significantly higher in DN patients (20±17 ng/ml) as compared to NA patients (10±6 ng/ml). When all 387 patients were included, stepwise regression analysis revealed a correlation between log plasma CTGF and log plasma creatinine levels (R=0.60, p<0.001). In addition, systolic blood pressure, log UAER, age and BMI also contributed as predictors of CTGF plasma level (cumulative R=0.64). When subgroups of patients were analysed separately, the correlation between log plasma CTGF and log plasma creatinine levels was present in the DN group (R=0.65, p<0.001) but absent in NA patients (R=0.018, p=0.81).

CTGF plasma levels are increased in type 1 DM patients with DN. Furthermore, a correlation between plasma CTGF and plasma creatinine levels was found. The relative contributions of decreased filtration and increased production of CTGF in patients with DN remain to be established.

Disclosure - Grant/Research Support: Fibrogen Inc.