Pathological Significance of a Panel of Urinary Biomarkers in Patients with Drug-Induced Tubulointerstitial Nephritis

Abstract

BACKGROUND AND OBJECTIVES: Although a renal biopsy is indispensable for depicting the severity of pathologic lesions in drug-induced tubulointerstitial nephritis (DTIN), it is not acceptable in some cases and cannot be performed serially because of its invasive nature. Therefore, the discovery of noninvasive markers that are closely related to the pathology of DTIN is of great value. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this study, the urinary levels of monocyte chemotactic peptide-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-d-glucosaminidase, and α1-microglobulin were measured in 40 DTIN subjects, and the performances of these parameters for distinguishing different pathologic lesions were compared. RESULTS: Linear correlation and receiver operating characteristic curve analyses showed that urinary MCP-1 levels were able to identify serious interstitial edema and inflammatory infiltration with greater accuracy than the other biomarkers (r = 0.501, P < 0.001 and r = 0.768, P < 0.001, respectively), whereas urinary NGAL levels showed the highest correlation coefficient with tubular atrophy (r = 0.692, P < 0.001). CONCLUSIONS: These results suggest that these biomarker levels were higher in patients with DTIN than in controls. Urinary MCP-1 levels correlated and were predictive of the gradated severity of acute lesions in DTIN, whereas the roles of NGAL and α1-microglobulin in chronic alterations require further study.