November 12, 2005
American Society of Nephrology (ASN) Renal Week 2005, Philadelphia, Pennsylvania
Abstract SA-PO361
Session: Prediction, Monitoring and Therapy; Clinical Diabetes

Elevated CTGF Levels are an Independent Risk Marker of Diabetic Vascular Disease. Ayad A. Jaffa ¹, William R. Usinger ³, M. Brent McHenry ², Stuart R. Lipstiz ², Daniel Lackland ², Louis M. Luttrell ¹, Peter WF. Wilson ¹, Maria Lopes-Virella ¹.

1 Department of Medicine, Division of Endocrinology-Diabetes-Medical Genetics, Medical and
2 Department of Bioinformatics, Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, South Carolina;
3 FibroGen, Inc., South San Francisco, California, and #NDIC/EDIC Bethesda, Maryland.

Abstract: Elevated levels of urinary and plasma CTGF have been recently shown to correlate with progression of DN in both Type I and Type II diabetics. Other studies implicate CTGF in the development of major comorbidities of DN, including cardiomyopathy and retinopathy, by virtue of its upregulation in pathological lesions. Thus, CTGF may serve as the central mechanistic link between diabetes and its major renal, cardiovascular and ocular consequences. We explored CTGF as a risk factor for the development of vascular complications in diabetic patients in a cross-sectional study in 1050 subjects with type 1 diabetes from the DCCT/EDIC Study cohort. We measured the circulating and urinary levels of CTGF by sandwich ELISA and found that plasma levels of CTGF were highly correlated to systolic BP (P<0.0001). CTGF levels also formed a significant and independent correlation with log AER, independent of the influence of BP on AER (P<0.0001). Patients with macroalbuminuria had significantly higher levels of CTGF than did normo- or microalbuminuric patients (P<0.0001). Uni- and multivariant regression analysis demonstrated that CTGF correlated significantly with increases in carotid intimal medial thickness (IMT), a surrogate marker of vascular disease, and formed a Relative Risk of 4.76 in macroalbuminurics relative to nomoalbuminurics (P<0.0001). The contribution of CTGF to increased risk for IMT was independent of patient age, gender, and BP and provided an additional significant risk of increased IMT beyond the risk contributed by elevated albuminuria. These findings confirm that levels of CTGF mark progression from diabetic kidney disease through overt nephropathy and demonstrate that increased levels of plasma CTGF in type I diabetic patients are an independent risk factor for vascular disease.