Evaluation of urinary biomarkers for the prognosis of drug-associated chronic tubulointerstitial nephritis.

BACKGROUND

The efficacy of urinary biomarkers for predicting adverse clinical outcomes in drug-induced chronic tubulointerstitial nephritis (D-CTIN) has not been well described.

METHODS

A total of 54 patients with D-CTIN were prospectively followed-up in this study. The urinary excretion of α1-microglobulin and transforming growth factor-β1 and the activity of urinary N-acetyl-β-D-glucosaminidase (NAG) and matrix metalloproteinases (MMPs) 2 and 9 at baseline were measured. Changes in the estimated glomerular filtration rate (GFR) over a period of 11 to 54 months (median, 38 months) of follow-up were recorded. The efficacy of urinary biomarkers for differentiating patients with various outcomes was tested. Ten patients with IgA nephropathy and 20 healthy volunteers were enrolled as controls.

RESULTS

The areas under the receiver operating characteristic curve for urinary NAG, MMP-9, MMP-2 and α1-microglobulin for predicting deterioration of the estimated GFR were 0.879, 0.867, 0.735 and 0.709, respectively (P < 0.05 for all). Partial regression coefficient results demonstrated that urinary NAG (P = 0.02), MMP-2 (P = 0.046) and MMP-9 (P = 0.041) were inversely correlated with the rate of GFR decline.

CONCLUSIONS

Urinary NAG, MMP-2 and MMP-9 may be considered as possible candidates for forecasting the progression rate of D-CTIN.