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


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.
Nguyen
Tri Q
TQ
Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
Tarnow
Lise
L
Jorsal
Anders
A
Oliver
Noelynn
N
Roestenberg
Peggy
P
Ito
Yasuhiko
Y
Parving
Hans-Henrik
HH
Rossing
Peter
P
van Nieuwenhoven
Frans A
FA
Goldschmeding
Roel
R
D000328:Adult; D015415:Biomarkers / Q000097:blood; D055513:Connective Tissue Growth Factor; D003928:Diabetic Nephropathies / Q000150:complications* / Q000401:mortality; D003930:Diabetic Retinopathy / Q000453:epidemiology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000401:mortality*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors
D015415:Biomarkers; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor