Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis
Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis
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DOI：
10.1172/jci.insight.127456
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发表时间：
2019-05-16
期刊：
影响因子：
8
通讯作者：
Parikh, Chirag R.
中科院分区：
文献类型：
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作者：
Moledina, Dennis G.;Wilson, F. Perry;Parikh, Chirag R.
背景急性间质性肾炎（AIN）的临床诊断具有挑战性，因为缺乏诊断生物标志物，需要肾活检。我们假设AIN是由特异性T细胞亚群介导的，因此特异性T细胞细胞因子水平可以作为区分AIN与其他急性肾脏疾病（AKD）病因的生物标志物。我们入组了2015年至2018年期间在2家中心接受肾活检以进行AKD评价的连续采样受试者。三位病理学家通过审查肾活检独立确立了AIN诊断。通过对12种选定的尿液和血浆细胞因子的单变量和多变量分析，我们确定了2种诊断为AIN。在218名参与者中，32名（15%）被所有3名病理学家诊断为AIN。AIN参与者的尿TNF-α和IL-9水平始终高于其他诊断，包括急性肾小管损伤，肾小球疾病和糖尿病肾病，以及那些没有任何肾脏疾病。与最低四分位数的参与者相比，我们注意到在控制血嗜酸性粒细胞、白细胞尿和蛋白尿时，TNF-α水平（校正比值比，10.9 [1.8，65.9]）和IL-9水平（7.5 [1.2，45.7]）最高四分位数的参与者中AIN的几率更高。添加生物标志物改善了临床医生活检前诊断的受试者工作特征曲线下面积（0.84 [0.78，0.91] vs. 0.62 [（0.53，0.71]）和当前测试模型（0.84 [0.76，0.91] vs. 0.69 [0.58，0.80]）。纳入尿TNF-α和IL-9可提高对临床医生活检前诊断和目前可用的AIN诊断测试的区分度。
BACKGROUND. Clinical diagnosis of acute interstitial nephritis (AIN) is challenging because of lack of a diagnostic biomarker and requires a kidney biopsy. We hypothesized that AIN is mediated by specific T cell subsets such that specific T cell cytokine levels could serve as biomarkers to distinguish AIN from other causes of acute kidney disease (AKD).METHODS. We enrolled consecutive sampling participants who underwent a kidney biopsy for AKD evaluation at 2 centers between 2015 and 2018. Three pathologists independently established AIN diagnosis through review of kidney biopsies. Through univariable and multivariable analysis of 12 selected urine and plasma cytokines, we identified 2 that were diagnostic of AIN.RESULTS. Of the 218 participants, 32 (15%) were diagnosed with AIN by all 3 pathologists. Participants with AIN had consistently higher levels of urine TNF-alpha and IL-9 than those with other diagnoses, including acute tubular injury, glomerular diseases, and diabetic kidney disease, and those without any kidney disease. As compared with participants in the lowest quartile, we noted higher odds of AIN in participants in the highest quartiles of TNF-alpha, levels (adjusted odds ratio, 10.9 [1.8, 65.9]) and IL-9 levels (7.5 [1.2, 45.7]) when controlling for blood eosinophils, leukocyturia, and proteinuria. Addition of biomarkers improved area under receiver operating characteristic curve over clinicians' prebiopsy diagnosis (0.84 [0.78, 0.91]) vs. 0.62 [(0.53, 0.71]) and a model of current tests (0.84 [0.76, 0.91] vs. 0.69 [0.58, 0.80]).CONCLUSIONS. Inclusion of urinary TNF-alpha and IL-9 improves discrimination over clinicians' prebiopsy diagnosis and currently available tests for AIN diagnosis.