Urinary Transforming Growth Factor-β1 is a Robust Predictor of Kidney Disease Progression

Abstract

Background: TGF-beta1 is the main fibrogenic cytokine associated with human glomerulonephritis. TGF-beta1 levels were found to be significantly increased in the urine of patients with IgA nephropathy. However, urinary TGF-beta1 excretion has so far not been evaluated with respect to the risk of kidney disease progression.

Methods: In the current study, urine samples were taken for TGF-beta1 protein analysis from 37 patients diagnosed with IgA nephropathy on the day of renal biopsy, and patients were followed until either the date of serum creatinine doubling or until the end of the follow-up period.

Results: The median follow-up was 3.6 years (range, 0.4-6.2 years). Urinary TGF-beta1/creatinine ratios (TGF-beta1/Cr, pg/mg) were significantly higher in IgA nephropathy patients than in normal controls (10.7+/-1.92 versus 2.38+/-0.52). The area under the receiver-operating-characteristics curve was 0.78 (P<0.05, 95% confidence interval 0.61-0.90), indicating that urinary TGF-beta1/Cr is an excellent predictor of kidney disease progression. Univariate Cox regression analysis showed that urinary TGF-beta1/Cr was the most powerful predictor of serum creatinine doubling (p=0.0026, relative risk 1.09, 95% confidence interval 1.03-1.15). Furthermore, multivariate Cox regression analysis adjusted for other confounders revealed that urinary TGF-beta1/Cr was the only significant predictor of serum creatinine doubling. In contrast, serum TGF-beta1 levels were not found to be a risk factor of kidney disease progression.

Conclusion: Our findings provide new evidence of a robust association between urinary TGF-beta1 and kidney disease progression in patients with IgA nephropathy.