Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.
Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.
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DOI：
10.3109/10428194.2014.897701
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发表时间：
2014-12
影响因子：
2.6
通讯作者：
van Besien K
中科院分区：
文献类型：
--
作者：
Petri CR;O'Donnell PH;Cao H;Artz AS;Stock W;Wickrema A;Hard M;van Besien K
我们研究了62名患者的氯法拉滨药代动力学及其与肾毒性的关系，这些患者参与了一项用于造血干细胞移植(HSCT)的氯法拉滨-马法兰-阿伦图珠单抗调理的I-II期研究。测量药物动力学参数，包括浓度-时间曲线下的面积(AUC)、最大浓度和清除量，并监测患者的肾脏损害。所有患者治疗前肌酐值正常，但超过一半(55%)的患者在服用氯法拉滨后发生急性肾损伤(AKI)。年龄是急性心肌梗死的最强预测因子，年龄越大风险越大(p=0.002)。发生AKI的患者氯法拉滨AUC较高，AUC剂量标准化程度最高的患者AKI严重程度最高(p=0.01)。较低的基线肾功能，即使在正常的情况下，也与较低的氯法拉滨清除率相关(p=0.008)。这些数据表明，即使肾功能表面上是正常的，也应该考虑对老年和高危患者进行肾调整氯法拉滨的剂量。
We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I–II study of clofarabine–melphalan–alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration–time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
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