Cheng Dao-Hai, Lu Hua, Liu Tao-Tao, Zou Xiao-Qin, Pang Hui-Mei
Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department Scientific Research, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Chemotherapy. 2018 Apr 19;63(2):101-107. doi: 10.1159/000486823.
Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL.
We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016. The clinical data were compared between the groups of children with development of AKI and those without. Risk factors were identified by multiple logistic regression analysis, and the diagnostic performance of plasma MTX concentration was evaluated by receiver operating characteristic (ROC) curve analysis.
AKI was observed in 88 patients (26.2%) and 104 courses (7.8%). Binary logistic regression revealed that age (OR 1.349; p = 0.005), first HDMTX course (OR 1.767; p = 0.013), MTX dose per body surface area (BSA; OR 1.944; p = 0.015), and baseline serum total protein (OR 0.929; p = 0.021) significantly correlated with AKI. The area under the ROC for 48-h plasma MTX concentration was 0.890 (95% CI 0.850-0.930), and sensitivity and specificity values of the cut-off value were 78.8 and 90.4%, respectively.
Increasing age, higher MTX dose per BSA, lower baseline serum protein, and first HDMTX course were significant risk factors for developing HDMTX-induced AKI in childhood ALL. The threshold of 48-h MTX plasma concentration is valuable for the prediction of HDMTX-induced AKI.
尽管大剂量甲氨蝶呤（HDMTX）是治疗急性淋巴细胞白血病（ALL）的有效手段，但肾功能障碍的发生仍然是一个重大的管理挑战。本研究旨在确定儿童ALL中HDMTX诱导的急性肾损伤（AKI）的关键因素。
我们回顾性分析了2012年9月至2016年11月在广西医科大学第一附属医院接受336例中国ALL儿童的1329个HDMTX治疗疗程的临床资料。比较了发生AKI的儿童组和未发生AKI的儿童组的临床资料。通过多因素logistic回归分析确定危险因素，并通过受试者工作特征（ROC）曲线分析评估血浆MTX浓度的诊断性能。
88例患者（26.2%）和104个疗程（7.8%）观察到AKI。二元logistic回归显示，年龄（OR 1.349；p = 0.005）、首次HDMTX疗程（OR 1.767；p = 0.013）、每体表面积（BSA）的MTX剂量（OR 1.944；p = 0.015）和基线血清总蛋白（OR 0.929；p = 0.021）与AKI显著相关。48小时血浆MTX浓度的ROC曲线下面积为0.890（95%CI 0.850 - 0.930），临界值的敏感性和特异性分别为78.8%和90.4%。
年龄增加、每BSA的MTX剂量较高、基线血清蛋白较低以及首次HDMTX疗程是儿童ALL中发生HDMTX诱导的AKI的重要危险因素。48小时MTX血浆浓度阈值对预测HDMTX诱导的AKI有价值。
