Nguyen Mai T, Dent Catherine L, Ross Gary F, Harris Nathan, Manning Peter B, Mitsnefes Mark M, Devarajan Prasad
Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Pediatr Nephrol. 2008 Aug;23(8):1317-26. doi: 10.1007/s00467-008-0827-9. Epub 2008 May 28.
Proteomic analysis has revealed potential early biomarkers of acute kidney injury (AKI) in children undergoing cardiopulmonary bypass (CPB), the most prominent one with a mass-to-charge ratio of 6.4 kDa. The objective of this study was to identify this protein and test its utility as a biomarker of AKI. Trypsin-digested protein bands were analyzed by tandem mass spectrometry (MS/MS) to identify the protein in urine samples. Surface-enhanced laser desorption/ionization time-of-flight analysis and a functional activity assay were performed to quantify urinary levels in a pilot study of 106 pediatric patients undergoing CPB. The protein was identified as aprotinin. Urinary aprotinin levels 2 h after initiation of CPB were predictive of AKI (for functional assay: 92% sensitivity, 96% specificity, area under the curve of 0.98). By multivariate analysis, the urinary aprotinin level 2 h after CPB was an independent predictor of AKI (beta = 0.001, P < 0.0001). The 2 h urinary aprotinin level correlated with serum creatinine, duration of AKI, and length of hospital stay. We concluded that urinary aprotinin levels 2 h after initiation of CPB predict the development of AKI and adverse clinical outcomes.
蛋白质组学分析揭示了接受体外循环（CPB）的儿童急性肾损伤（AKI）的潜在早期生物标志物，其中最突出的一种质荷比为6.4 kDa。本研究的目的是鉴定这种蛋白质，并测试其作为AKI生物标志物的效用。通过串联质谱（MS/MS）分析胰蛋白酶消化的蛋白条带，以鉴定尿液样本中的蛋白质。在一项对106例接受CPB的儿科患者的初步研究中，进行了表面增强激光解吸/电离飞行时间分析和功能活性测定，以量化尿液水平。该蛋白质被鉴定为抑肽酶。CPB开始后2小时的尿抑肽酶水平可预测AKI（功能测定：敏感性92%，特异性96%，曲线下面积0.98）。通过多变量分析，CPB后2小时的尿抑肽酶水平是AKI的独立预测因子（β = 0.001，P < 0.0001）。CPB后2小时的尿抑肽酶水平与血清肌酐、AKI持续时间和住院时间相关。我们得出结论，CPB开始后2小时的尿抑肽酶水平可预测AKI的发生和不良临床结局。
