Correlation between urinary biomarkers and pathological lesions in drug-induced tubulointerstitial nephritis

Abstract

To find some urinary biomarkers for differential diagnosis in drug-induced tubulointerstitial nephritis (DTIN) by accessing the relationship between their changes and the pathological processes of DTIN. Forty patients biopsy-proven DTIN and 24 healthy controls were enrolled in this study. The urine samples of DTIN patients were collected on the day of biopsy and were measured for the following biomarkers: urinary TGF-β with enzyme-linked immunosorbent assay (ELISA); urinary IL-6 with radio-immunoassay; N-acetyl-β-D-glucosaminidase (NAG) with enzyme-substrate colorimetric assay; α1-microglobulin (α1-MG) with immune transmission turbidity method. Meanwhile, the pathological changes on renal biopsy were analyzed semi-quantitatively and scored. The relationship between these pathological changes and the urinary biomarkers were analyzed and receiver operating characteristic curve (ROC curve) of those biomarkers in distinguishing different pathological lesions were constructed. Urinary α1-MG levels were positively correlated to interstitial edema, inflammatory cell infiltration and tubular atrophy, while urinary IL-6 were negatively correlated to the above parameters. Urinary NAG had positive relationship with inflammatory cell infiltration and tubular atrophy, while urinary TGF-β had positive relationship with tubular atrophy. ROC analysis results indicated that the area under curve (AUC) of α1-MG was larger than that of NAG (0.797 vs 0.734, P<0.05). Combined measurement of α1-MG and NAG could enhance the sensitivity of detecting interstitial inflammatory cell infiltration. For detecting interstitial edema and tubular atrophy, only α1-MG had statistical significance (AUC=0.723, P=0.027; AUC=0.774, P=0.008, respectively). Urinary α1-MG and NAG levels can reflect the severity of interstitial inflammatory infiltration, combined measurement of both can enhance sensitivity. Urinary α1-MG level can also reflect the degree of interstitial edema and tubular atrophy.