Beger Richard D, Holland Ricky D, Sun Jinchun, Schnackenberg Laura K, Moore Page C, Dent Catherine L, Devarajan Prasad, Portilla Didier
Division of Systems Toxicology, United States Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Pediatr Nephrol. 2008 Jun;23(6):977-84. doi: 10.1007/s00467-008-0756-7.
Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.
急性肾损伤（AKI）是接受体外循环手术儿童的主要并发症。我们对40名接受先天性心脏缺陷矫正心脏手术的儿童的尿液样本进行了代谢组学分析。在手术前以及手术后4小时和12小时从每位患者获取系列尿液样本。在心脏手术后48 - 72小时，21名儿童出现AKI，定义为血清肌酐基线水平升高50%或更多。对发生AKI的患者术后4小时和12小时获取的尿液样本的液相色谱/质谱（LC/MS）负离子化数据进行主成分分析，结果显示发生AKI的患者与未发生AKI的患者聚类分离。对质荷比（m/z）261.01、保留时间（tR）4.92分钟的LC/MS峰通过串联质谱（MS/MS）进一步分析，鉴定为多巴胺代谢产物硫酸高香草酸（HVA - SO4）。通过MS单反应监测，术后12小时HVA - SO4的截断值为24 ng/微升时，灵敏度为0.90，特异性为0.95。我们得出结论，尿液HVA - SO4是小儿心脏手术后AKI一种新的、敏感的且具有预测性的早期生物标志物。
