November 12-17, 2003
American Society of Nephrology (ASN) Renal Week 2003, San Diego, CA.

Human Urinary CTGF (CCN2) as a Predictor of Progression of Chronic Renal Diseases. Yasuhiko Ito, Hirotake Kasuga, Fujita Yoshirou, Yukio Yuzawa, Seiichi Matsuo, Noelynn Oliver, William Usinger, Stephen Weitz, Evelene Lomongsod. 1 Internal Medicine, Chubu Rousai Hospital, Nagoya, Japan; Clinical Immunology, Nagoya University, Nagoya, Japan; FibroGen, Inc., South San Francisco, CA.

We have previously shown that connective tissue growth factor (CTGF/CCN2), a potent prosclerotic growth factor that mediates downstream effects of TGF, is upregulated in human and rat progressive renal diseases. We examined production and excretion of CTGF in the urine as a predictor of progression of renal dysfunction in diabetic nephropathy (DMN) and non-diabetic renal diseases (non-DMN). CTGF levels were measured in urine (n=312) of patients with type 2 diabetes, minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), IgA nephropathy (IgAN), focal glomerular sclerosis (FGS), nephrosclerosis (NS), hypertension, and healthy subjects using a sandwich ELISA that is specific for the N-terminal portion of CTGF. DMN was classified into five stages: normoalbuminuria, microalbuminuria, macroalbuminuria, renal insufficiency (RI), and renal failure (RF). CTGF values were standardized by urinary creatinine content.

Urinary CTGF (U-CTGF) content was significantly higher in RI and RF of DMN, NS, IgAN, and FGS than in healthy control. In both DMN and in non-DMN, the level of U-CTGF was inversely proportional to renal function. A positive and significant correlation between U-CTGF content and proteinuria was observed in DMN, however U-CTGF was not elevated in glomerular diseases characterized by non-inflammatory lesions and heavy proteinuria, ie. MCNS and MN. U-CTGF content was relatively higher in DMN than in non-DMN.

We additionally measured U-CTGF levels every 3 - 4 months for 18 months in 12 patients with DMN and 2 patients with IgAN. Increased U-CTGF was correlated with extent of renal deterioration in all 7 diabetic patients whose renal function became worse. Furthermore, U-CTGF decreased in 2 diabetic patients whose renal function gradually improved during treatment with ACE-inhibitor or Angiotensin II receptor antagonist. These findings suggest that urinary CTGF is a predictor of renal disease progression and response to therapy.