Plasma Connective Tissue Growth Factor Is an Independent Predictor of End-Stage Renal Disease and Mortality in Type 1 Diabetic Nephropathy

  1. Tri Q. Nguyen, MD1,
  2. Lise Tarnow, MD, DMSC2,
  3. Anders Jorsal2,
  4. Noelynn Oliver, PHD3,
  5. Peggy Roestenberg, PHD1,
  6. Yasuhiko Ito, MD4,
  7. Hans-Henrik Parving, MD, DMSC56,
  8. Peter Rossing, MD, DMSC2,
  9. Frans A. van Nieuwenhoven, PHD1 and
  10. Roel Goldschmeding, MD, PHD1
  1. 1Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Steno Diabetes Center, Gentofte, Denmark
  3. 3FibroGen, South San Francisco, California
  4. 4Nephrology, Nagoya University School of Medicine, Nagoya, Japan
  5. 5Endocrinology, Rigshospitalet, Copenhagen, Denmark
  6. 6Faculty of Health Science, Aarhus University, Aarhus, Denmark
  1. Corresponding author: R. Goldschmeding, MD, PhD, UMC Utrecht, Department of Pathology, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands. E-mail: r.goldschmeding{at}umcutrecht.nl

Abstract

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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 14 March 2008. DOI: 10.2337/dc07-2469.

    P.G. is currently affiliated with Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. F.A.N. is currently affiliated with Physiology, Cardiovascular Research, Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.

    R.G. has received research support grants and consulting fees from FibroGen.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted March 7, 2008.
    • Received December 31, 2007.
« Previous | Next Article »Table of Contents

This Article

  1. Published online before print March 14, 2008, doi: 10.2337/dc07-2469 Diabetes Care June 2008 vol. 31 no. 6 1177-1182
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. All Versions of this Article:
    1. dc07-2469v1
    2. 31/6/1177 most recent

Current Issue

  1. December 2009, 32 (12)
  1. Current Issue
  1. Alert me to new issues of Diabetes Care