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Published online March 14, 2008
Diabetes Care 31:1177-1182, 2008
DOI: 10.2337/dc07-2469
© 2008 by the American Diabetes Association
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Pathophysiology/Complications
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

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

Corresponding author: R. Goldschmeding, MD, PhD, UMC Utrecht, Department of Pathology, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands. E-mail: r.goldschmeding{at}umcutrecht.nl

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 m2 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.

Abbreviations: CTGF, connective tissue growth factor • ESRD, end-stage renal disease • GFR, glomerular filtration rate • ROC, receiver operating characteristic • UAE, urinary albumin excretion


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