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Diabetes Care Publish Ahead of Print published online ahead of print March 14, 2008
DOI: 10.2337/dc07-2469
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Original Research

Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

Tri Q. Nguyen, MD1, Lise Tarnow, MD, DMSC2, Anders Jorsal2, Noelynn Oliver, PHD3, Peggy Roestenberg, PHD1, Yasuhiko Ito, MD4, Hans-Henrik Parving, MD, DMSC5,,6, Peter Rossing, MD, DMSC2, Frans A. van Nieuwenhoven, PHD1 and Roel Goldschmeding, MD, PHD1

1Pathology, University Medical Center Utrecht, Utrecht, Netherlands
2Steno Diabetes Center, Gentofte, Denmark
3FibroGen, Inc, South San Francisco, CA, USA
4Nephrology, Nagoya University School of Medicine, Nagoya, Japan
5Endocrinology, Rigshospitalet, Copenhagen, Denmark, and
6Faculty of Health Science, Aarhus University, Aarhus, Denmark

R.Goldschmeding{at}umcutrecht.nl

ABSTRACT

Objective: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF; CCN-2) 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 pmol/l [interquartile range 270-630] vs. 235 [168-353]). In patients with nephropathy, elevated plasma CTGF was an independent predictor of ESRD (covariate-adjusted hazard ratio 1.6 [95% CI 1.1-2.5]), and correlated with the rate of decline in GFR (cumulative R=0.46). Area under the ROC 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 (5.4±4.9 ml/min/1.73 m2/year vs. 3.3±3.5). Moreover, in patients with nephrotic range albuminuria (>3 g/day), plasma CTGF was the only predictor of ESRD (covariate-adjusted hazard ratio 4.5 [2.0-10.4]). Plasma CTGF was an independent predictor also of overall mortality (covariate-adjusted hazard ratio 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.


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