The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis

Objective: The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Methods: Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. Results: The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 +/- 12.17 ng/ml vs. 22.8 +/- 3.0 ng/ml, p<0.001; 44.1 +/- 46.8 ng/ml vs. 22.8 +/- 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 +/- 12.17 ng/ml vs. 44.1 +/- 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 +/- 51.4 ng/ml vs. 23.4 +/- 9.7 ng/ml, p<0.001) and acute renal failure (85.5 +/- 75.0 ng/ml vs. 31.2 +/- 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 +/- 57.5 ng/ml vs. 18.7 +/- 6.4 ng/ml, p = 0.019; 57.6 +/- 57.5 ng/ml vs. 25.2 +/- 14.9 ng/ml, p = 0.006; 57.6 +/- 57.5 ng/ml vs. 30.5 +/- 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 +/- 69.6 ng/ml vs. 40.0 +/- 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 +/- 63.4 ng/ml vs. 38.3 +/- 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis. Conclusions: Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis.