几种尿标志物在急性药物性肾小管间质性肾炎鉴别诊断中的意义

Significance of urinary biomarkers in differential diagnosis of acute tubulointersitial nephritis

目的:通过对药物性肾小管间质性肾炎(DTIN)患者尿标志物临床病理相关性的研究,发现对鉴别急性DTIN(A-DTIN)和慢性DTIN(C-DTIN)有意义的尿标志物。方法:共40例肾活检确诊的DTIN患者入选,取肾活检当日的尿标本,用双抗体夹心酶联免疫吸附(ELISA)法检测TGF-β,放射性酶联免疫法(RIA)检测IL-6,酶-底物直接显色法检测NAG,免疫透射比浊法检测α1-MG。通过构建受试者工作曲线(ROC)来计算各尿液指标鉴别A-DTIN的敏感性及特异性。结果:A-DTIN组的尿NAG和尿α1-MG分别是C-DTIN组的2.5和2.1倍(P值均<0.05),而尿TGF-β水平在A-DTIN组和C-DTIN组之间差异无统计学意义。尿α1-MG和NAG鉴别A-DTIN的曲线下面积分别为0.720(P=0.029)和0.714(P=0.034),而尿TGF-β的曲线下面积为0.536,无统计学意义(P=0.767),尿IL-6的曲线下面积为0.150(P=0.004)。将尿α1-MG和NAG进行联合能使敏感性和特异性分别达到78.6%和75.0%。结论:尿α1-MG和NAG水平能反映DTIN的急性损伤,二者联合检测能提高鉴别诊断A-DTIN的效率。

Objective：To find some urinary biomarkers with significance in the differentiation of drug-induced tubulointersitial nephritis（DTIN）.Methods： Forty patients with biopsy-proven DTIN were enrolled.The urine samples of DTIN patients were collected on the day of biopsy and all urine samples were measured for the following different biomarkers as indicated,respectively： urinary TGF-β by ELISA;urinary IL-6 by radio-immunoassay;NAG by an enzyme-substrate colorimetric assay;α1-MG by immune transmission turbidity method.Receiver operating characteristic curves（ROC curve） were constructed to calculate the sensitivity and specificity of those biomarkers in distinguishing acute（A-DTIN） and chronic DTIN（C-DTIN）.Results： Urinary NAG and α1-MG levels in patients with A-DTIN were as 2.5 and 2.1 times as those in C-DTIN（P〈0.05）,while urinary TGF-β levels in the two groups had no statistical difference.The areas under ROC curve（AUC） of urinary NAG and α1-MG for differentiating A-DTIN were 0.720（P=0.029） and 0.714（P=0.034） respectively,while the AUCs for TGF-β and IL-6 were 0.536（P=0.767） and 0.150（P= 0.004） respectively.Combined measurement of NAG and α1-MG could make sensitivity and specificity reach 78.6% and 75.0 % respectively.Conclusion：Urinary α1-MG and NAG levels can reflect the acute lesions of DTIN,and combined measurement of both could enhance efficiency in differentiating A-DTIN.