November 2, 2007
American Society of Nephrology (ASN) Renal Week 2007, San Francisco, CA
Abstract F-PO1013

Plasma connective tissue growth factor (CTGF; CCN-2) predicts end-stage renal disease and mortality in type 1 diabetic nephropathy. TQ Nguyen¹, L Tarnow², A Jorsa², N Oliver³, P Roestenberg¹, Y Ito⁴, FA van Nieuwenhoven¹, HH Parving² and R Goldschmeding¹.

1 Pathology, UMCU, Utrecht, Netherlands; 2 Steno Diabetes Center, Gentofte, Denmark; 3 FibroGen, Inc., South San Francisco, CA, United States and 4 Nephrology, University School of Medicine, Nagoya, Japan.

Background: Levels of CTGF in plasma are increased in experimental and human diabetic nephropathy. However, it is not known whether plasma CTGF might also be useful as a prognostic marker.

Methods: We evaluated the predictive value of baseline plasma CTGF for outcome and disease progression in a large prospective study. Subjects were 198 type 1 diabetic patients with overt diabetic nephropathy, and 188 type 1 diabetic patients with persistent normoalbuminuria. Follow-up time was 12.8 years. Plasma CTGF was measured at baseline by sandwich ELISA.

Results: In patients with nephropathy, addition of plasma CTGF content increased the correlation of urinary albumin excretion (UAE) with the rate of decline in GFR (cumulative R=0.46). Area under the ROC curve for prediction of end-stage renal disease (ESRD) by plasma CTGF was 0.74. A cutoff value of 394 pmol/L predicted ESRD with a sensitivity of 76% and a specificity of 61%. In addition, a standardized (1-SD) increase in plasma CTGF independently predicted ESRD [covariate-adjusted hazard ratio 1.6 (95% CI 1.1-2.5), P=0.03]. This was most prominent for patients in the highest UAE quartile [>2050 mg/day; covariate-adjusted hazard ratio 2.4 (1.3-4.2), P=0.003]. Of note, difference in UAE among patients within this quartile no longer predicted outcome. This points to unique potential application of plasma CTGF as a prognosticator of renal function in patients with more severe proteinuria. Furthermore, plasma CTGF content was an independent predictor of overall mortality in patients with diabetic nephropathy [covariate-adjusted hazard ratio 1.4 (1.1-1.8), P=0.003]. In contrast, in normoalbuminuric patients, plasma CTGF did not predict outcome nor correlate with clinical parameters.

Conclusion: Addition of plasma CTGF content to conventional risk factor assessment significantly improves prediction of ESRD and mortality in patients with overt type 1 diabetic nephropathy.

See also November 7, 2007 press release