Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Pediatr Nephrol. 2017 Dec;32(12):2351-2360. doi: 10.1007/s00467-017-3748-7. Epub 2017 Jul 28.
Several novel biomarkers that predict acute kidney injury (AKI) have recently been proposed. We have evaluated the sequential patterns of biomarker elevation after pediatric cardiopulmonary bypass (CPB) and determined their diagnostic accuracy.
We measured the ability of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7), to predict AKI (≥50% increase in serum creatinine from baseline). Areas under the receiver-operator characteristic curves (AUCs) were calculated for each biomarker and for various biomarker combinations at multiple time points after CPB.
Of 150 patients examined, AKI had developed in 50 patients by 24 h after CPB, with an elevated NGAL concentration first noted at 2 h post-CPB, increases in IL-18, L-FABP, and the product of TIMP-2 and IGFBP7 first noted at 6 h, and an elevated KIM-1 level noted at 12 h. At each time point, urine NGAL remained the marker with the highest predictive ability (AUC > 0.9). The addition of any other biomarker did not increase the predictive accuracy of NGAL alone at 2 and 6 h. At 12 h, when compared to NGAL alone, the combination of NGAL, IL-18, and TIMP2 improved the AUC for AKI prediction (from 0.938 to 0.973).
While urine NGAL remains a superior stand-alone test at the 2 and 6 h time points after pediatric CPB, a panel of carefully selected biomarkers may prove optimal at later time points.
最近提出了几种预测急性肾损伤（AKI）的新型生物标志物。我们评估了儿科体外循环（CPB）后生物标志物升高的顺序模式，并确定了它们的诊断准确性。
我们测量了中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、白细胞介素-18（IL-18）、肝型脂肪酸结合蛋白（L-FABP）、肾损伤分子-1（KIM-1）、金属蛋白酶组织抑制剂-2（TIMP-2）和胰岛素样生长因子结合蛋白 7（IGFBP7）的能力，以预测 AKI（从基线到血清肌酐增加≥50%）。计算了每个生物标志物在 CPB 后多个时间点的受试者工作特征曲线（AUC）下面积，并计算了各种生物标志物组合的 AUC。
在检查的 150 名患者中，50 名患者在 CPB 后 24 小时内发生 AKI，CPB 后 2 小时首次发现 NGAL 浓度升高，CPB 后 6 小时首次发现 IL-18、L-FABP 和 TIMP-2 和 IGFBP7 的产物升高，12 小时时 KIM-1 水平升高。在每个时间点，尿液 NGAL 仍然是预测能力最高的标志物（AUC > 0.9）。在 2 小时和 6 小时时，添加任何其他生物标志物都不会增加 NGAL 单独预测的准确性。在 12 小时时，与 NGAL 单独相比，NGAL、IL-18 和 TIMP2 的组合改善了 AKI 预测的 AUC（从 0.938 提高到 0.973）。
虽然尿液 NGAL 在儿科 CPB 后 2 小时和 6 小时仍然是一种优越的独立检测方法，但精心选择的生物标志物组合在后期时间点可能是最佳选择。
