Levels of Connective Tissue Growth Factor (CTGF) Predict Development of Kidney Dysfunction in Type 2 Diabetes-The VADT Study

Abstract

Connective tissue growth factor (CTGF) is a member of the CCN family of matricellular proteins that has been implicated in the inflammatory process, response to injury and wound healing. An emerging role of CTGF is that of a profibrotic factor implicated in the development of kidney disease. Our objective was to determine the role of CTGF as a predictor of macroalbuminuria (ACR ≥300µg/mg twice) and chronic kidney disease (CKD) stage 3 (GFR <60ml/min twice) and stage 4 (GFR <30ml/min once or twice) in the VADT cohort. Levels of CTGF were measured in 952 VADT patients, a median of 1.9 years after entry into the study. Participants were followed for a median of 3.8 years for renal outcomes. CTGF categories were defined as below the detectable limit (i.e., referent, 54.5%), lower half of detectable values (i.e., 22.8%) and upper half of detectable values (22.7%). Odds ratios (ORs) for kidney endpoints in relation to CTGF categories were calculated by logistic regression. Even with adjustment for baseline ACR levels, individuals in the highest compared to lowest CTGF category were at higher risk of macroalbuminuria [OR=3.21 (95% CI: 1.37, 7.53)]. In contrast, CTGF was predictive of incident stage 3 and stage 4 CKD only when baseline GFR levels were not adjusted for. Our study indicates that high levels of CTGF are associated with and predict future kidney dysfunction in patients with type 2 diabetes. Disclosure K.J. Hunt: None. M.A. Jaffa: None. S.M. Garrett: None. D.K. Luttrell: None. K.E. Lipson: Employee; Self; FibroGen, Inc.. Stock/Shareholder; Self; AbbVie Inc., Abbott, Becton, Dickinson and Company, Bristol-Myers Squibb Company, General Electric, Gilead Sciences, Inc., Medtronic, Nestlé, Novartis AG, Oracle, Pfizer Inc., Quest Diagnostics. Consultant; Spouse/Partner; Diabesen. M.F. Lopes-Virella: None. L.M. Luttrell: None. A.A. Jaffa: None.