Wu Yu, Su Tao, Yang Li, Wang Chen, Liu Gang, Li Xiao-mei
Renal Division, First Hospital, Peking University, Institute of Nephrology, Key Laboratory of the Ministry of Health, Beijing 100034, China.
Zhonghua Nei Ke Za Zhi. 2010 Jul;49(7):568-71.
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.
通过探讨尿液生物标志物变化与药物性肾小管间质性肾炎（DTIN）病理过程的关系，寻找用于DTIN鉴别诊断的尿液生物标志物。
本研究纳入40例经活检证实的DTIN患者和24例健康对照。在活检当天采集DTIN患者的尿液样本，检测以下生物标志物：采用酶联免疫吸附测定（ELISA）法检测尿转化生长因子-β（TGF-β）；采用放射免疫法检测尿白细胞介素-6（IL-6）；采用酶底物比色法检测N-乙酰-β-D-氨基葡萄糖苷酶（NAG）；采用免疫透射比浊法检测α1-微球蛋白（α1-MG）。同时，对肾活检的病理变化进行半定量分析并评分。分析这些病理变化与尿液生物标志物之间的关系，并构建这些生物标志物区分不同病理病变的受试者工作特征曲线（ROC曲线）。
尿α1-MG水平与间质水肿、炎性细胞浸润和肾小管萎缩呈正相关，而尿IL-6与上述参数呈负相关。尿NAG与炎性细胞浸润和肾小管萎缩呈正相关，而尿TGF-β与肾小管萎缩呈正相关。ROC分析结果表明，α1-MG的曲线下面积（AUC）大于NAG（0.797对0.734，P<0.05）。联合检测α1-MG和NAG可提高检测间质炎性细胞浸润的敏感性。对于检测间质水肿和肾小管萎缩，只有α1-MG具有统计学意义（AUC分别为0.723，P=0.027；AUC=0.774，P=0.008）。
尿α1-MG和NAG水平可反映间质炎性浸润的严重程度，联合检测两者可提高敏感性。尿α1-MG水平还可反映间质水肿和肾小管萎缩的程度。
