Wang Yujia, Wei Li, Guan Yi, Wang Qian, Xie Qionghong, Hao Chuanming
Division of Nephrology, Huashan Hospital, and Nephrology Research Institute, Fudan University, Shanghai, China.
Division of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
Ren Fail. 2020 Nov;42(1):1111-1117. doi: 10.1080/0886022X.2020.1838926.
The aim of the study was to investigate the incidence of acute kidney injury (AKI) occurring after high-dose methotrexate (HDMTX) administration and the role of type 2 diabetes (T2D) playing in the occurrence of AKI.
We assessed associations between T2D along with other confounding factors mainly including baseline estimated glomerular filtration rate (eGFR), methotrexate (MTX) elimination and urine pH, and AKI occurrence. Patients who were diagnosed as primary central nervous system lymphoma with treatment of HDMTX and with eGFR ≥60 mL/min/1.73 m were enrolled in this study.
Of the 507 courses enrolled in this study, 132 courses have T2D. Lower baseline eGFR, delayed MTX elimination, lower urine pH, and higher incidence of AKI were observed in T2D group. Using univariate logistic regression, several confounding factors including baseline eGFR, hypertension, MTX elimination, and urine alkalinization statistically and clinically important were screened out. After adjusting for these factors, T2D remained an independent association with AKI occurrence. AKI outcome had no significant relationship with severe hematological toxicity or hepatotoxicity. AKI was associated with faster eGFR decline after a series of HDMTX treatment courses.
Patients with T2D have a higher sensitivity to AKI when administrated with HDMTX. This conclusion addresses safety concerns for making chemotherapy regimen for this population.
本研究旨在调查大剂量甲氨蝶呤（HDMTX）给药后急性肾损伤（AKI）的发生率以及2型糖尿病（T2D）在AKI发生中所起的作用。
我们评估了T2D与其他主要混杂因素（包括基线估计肾小球滤过率（eGFR）、甲氨蝶呤（MTX）清除率和尿液pH值）之间的关联以及AKI的发生情况。本研究纳入了被诊断为原发性中枢神经系统淋巴瘤并接受HDMTX治疗且eGFR≥60 mL/min/1.73 m²的患者。
在本研究纳入的507个疗程中，132个疗程患有T2D。在T2D组中观察到较低的基线eGFR、MTX清除延迟、较低的尿液pH值以及较高的AKI发生率。使用单因素逻辑回归分析筛选出了包括基线eGFR、高血压、MTX清除率和尿液碱化等具有统计学和临床意义的混杂因素。在对这些因素进行调整后，T2D仍然是与AKI发生独立相关的因素。AKI的结局与严重血液学毒性或肝毒性无显著关系。在一系列HDMTX治疗疗程后，AKI与eGFR更快下降相关。
T2D患者在接受HDMTX治疗时对AKI的敏感性更高。这一结论解决了为该人群制定化疗方案时的安全性问题。
