Inflammatory cytokines as predictive markers for early detection and progression of diabetic nephropathy
OBJECTIVE We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic patients with persistent normoalbuminuria. Follow-up time was 12.8 years. Prediction of end-stage renal disease (ESRD) and mortality by plasma CTGF was analyzed in conjunction with conventional risk factors. RESULTS Plasma CTGF was higher in patients with nephropathy than in patients with normoalbuminuria (median 381 [interquartile range 270-630] vs. 235 [168-353] pmol/l). In patients with nephropathy, elevated plasma CTGF was an independent predictor of ESRD (covariate-adjusted hazard ratio [HR] 1.6 [95% CI 1.1-2.5]) and correlated with the rate of decline in glomerular filtration rate (GFR) (cumulative R = 0.46). Area under the receiver operating characteristic curve for prediction of ESRD was 0.72. Plasma CTGF above a cutoff level of 413 pmol/l predicted ESRD with a sensitivity of 73% and a specificity of 63% and was associated with a higher rate of decline in GFR (mean +/- SD 5.4 +/- 4.9 vs. 3.3 +/- 3.5 ml/min per 1.73 m(2) per year). Moreover, in patients with nephrotic range albuminuria (>3 g/day), plasma CTGF was the only predictor of ESRD (covariate-adjusted HR 4.5 [2.0-10.4]). Plasma CTGF was an independent predictor also of overall mortality (covariate-adjusted HR 1.4 [1.1-1.7]). In contrast, in normoalbuminuric patients, plasma CTGF did not correlate with clinical parameters and did not predict outcome. CONCLUSIONS Plasma CTGF contributes significantly to prediction of ESRD and mortality in patients with type 1 diabetic nephropathy.