急性肾损伤生物标志物比血清肌酐定义的急性肾损伤更早预测心脏手术后婴儿血清米力农浓度的升高。
Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine-Defined Acute Kidney Injury in Infants After Cardiac Surgery.
作者信息
Gist Katja M, Cooper David S, Wrona Julia, Faubel Sarah, Altmann Christopher, Gao Zhiqian, Marino Bradley S, Alten Jeffrey, Hock Kristal M, Mizuno Tomoyuki, Vinks Alexander A, Joy Melanie S, Wempe Michael F, Bennett Michael R, Goldstein Stuart L
机构信息
Division of Pediatric Cardiology, Department of Pediatrics, The Heart Institute, The University of Colorado, Children's Hospital Colorado, Aurora, Colorado.
Department of Pediatrics, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
出版信息
Ther Drug Monit. 2018 Apr;40(2):186-194. doi: 10.1097/FTD.0000000000000496.
BACKGROUND
Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery.
METHODS
Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Serum milrinone concentrations were measured at specific intervals after drug initiation, dose changes, and termination. Excessive milrinone activity was defined as a 20% increase in serum concentration between 6 and 36 hours after initiation. The temporal relationship between urinary AKI biomarker concentrations and a 20% increase in milrinone concentration was assessed.
RESULTS
AKI occurred in 31 (33%) of infants. Milrinone clearance was lower in patients with AKI (4.2 versus 5.6 L/h/70 kg; P = 0.02). Excessive milrinone activity was associated with development of serum creatinine-defined AKI [odds ratio (OR) 3.0; 95% confidence interval (CI), 1.21-7.39; P = 0.02]. Both tissue inhibitor metalloproteinase type 2 and insulin-like growth factor-binding protein type 7 (TIMP-2*IGFBP-7) ≥0.78 at 12 hours (OR 2.72; 95% CI, 1.01-7.38; P = 0.04) and kidney injury molecule 1 (KIM-1) ≥529.57 at 24 hours (OR 2.76; 95% CI, 1.06-7.17; P = 0.04) predicted excessive milrinone activity before a diagnosis of AKI.
CONCLUSIONS
In this pilot study, urine TIMP-2*IGFBP-7 and KIM-1 were predictive of AKI and excessive milrinone activity. Future studies that include a pharmacodynamics assessment of patient hemodynamics, excessive milrinone activity, and AKI biomarker concentrations may be warranted to integrate this concept into clinical practice.
背景
米力农是一种常用于心脏手术后儿童的正性肌力药物，在急性肾损伤（AKI）中会蓄积。我们评估了尿AKI生物标志物是否可预测心脏手术后婴儿米力农浓度的升高。
方法
对接受心脏手术的婴儿进行多中心前瞻性试点研究。在体外循环开始后的特定时间间隔测量尿液中的尿AKI生物标志物。AKI根据《改善全球肾脏病预后组织》血清肌酐标准进行定义。在药物开始使用、剂量改变和停药后的特定时间间隔测量血清米力农浓度。米力农活性过高定义为开始用药后6至36小时内血清浓度升高20%。评估尿AKI生物标志物浓度与米力农浓度升高20%之间的时间关系。
结果
31名（33%）婴儿发生了AKI。AKI患者的米力农清除率较低（4.2对5.6 L/h/70 kg；P = 0.02）。米力农活性过高与血清肌酐定义的AKI的发生相关[比值比（OR）3.0；95%置信区间（CI），1.21 - 7.39；P = 0.02]。在12小时时组织金属蛋白酶抑制剂2和胰岛素样生长因子结合蛋白7（TIMP - 2*IGFBP - 7）≥0.78（OR 2.72；95% CI，1.01 - 7.38；P = 0.04）以及在24小时时肾损伤分子1（KIM - 1）≥529.57（OR 2.76；95% CI，1.06 - 7.17；P = 0.04）可在AKI诊断前预测米力农活性过高。
结论
在这项试点研究中，尿TIMP - 2*IGFBP - 7和KIM - 1可预测AKI和米力农活性过高。未来可能需要进行包括对患者血流动力学、米力农活性过高和AKI生物标志物浓度进行药效学评估的研究，以将这一概念纳入临床实践。
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