Mertens Inge, Willems Hanny, Van Loon Elisabet, Schildermans Karin, Boonen Kurt, Baggerman Geert, Valkenborg Dirk, Gwinner Wilfried, Anglicheau Dany, Essig Marie, Marquet Pierre, Naesens Maarten
Health Unit, Centre for Proteomics, VITO, Mol, Belgium.
Centre for Proteomics, University of Antwerp, Antwerp, Belgium.
Kidney Int Rep. 2020 Jun 29;5(9):1448-1458. doi: 10.1016/j.ekir.2020.06.018. eCollection 2020 Sep.
Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation.
We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort, = 249) and an independent, prospective multicenter cohort study for validation ( = 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort.
We identified a set of 10 urinary proteins that accurately discriminated patients with ( = 60) and without ( = 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96-1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8-0.93) for discriminating the presence ( = 43) from the absence ( = 348) of ABMR. The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76).
We identified and validated a urinary protein biomarker set that can be used to exclude ABMR.
抗体介导的排斥反应（ABMR）会影响肾移植的结果。诊断基于侵入性肾移植活检标本的检查结果。本研究的目的是确定一种用于肾移植后ABMR的非侵入性尿液蛋白质生物标志物。
我们进行了一项多中心病例对照研究以确定ABMR的尿液生物标志物（训练队列，n = 249），并进行了一项独立的前瞻性多中心队列研究以进行验证（n = 391）。我们使用同步活检根据Banff分类对样本进行分类。在进行非靶向蛋白质鉴定和定量后，我们使用支持向量机在训练队列中训练模型。主要终点是验证队列中尿液生物标志物对ABMR的诊断准确性。
我们鉴定出一组10种尿液蛋白质，其在训练队列中能够准确区分患有（n = 60）和未患有（n = 189）ABMR的患者，曲线下面积（AUC）为0.98（95%置信区间[CI]，0.96 - 1.00）。在验证队列中，用于区分ABMR存在（n = 43）与不存在（n = 348）的诊断准确性得以维持（AUC，0.88；95%CI，0.8 - 0.93）。该10种蛋白质标志物组排除ABMR的阴性预测值为0.99，阳性预测值为0.33。诊断准确性与进行活检的原因、移植后的时间无关，且优于蛋白尿（AUC，0.76）的准确性。
我们鉴定并验证了一组可用于排除ABMR的尿液蛋白质生物标志物。
