Laboratory of Applied Statistics in the Health Sciences, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Resonance, Memphis, Tennessee, USA.
Cancer Med. 2024 Sep;13(17):e70176. doi: 10.1002/cam4.70176.
High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.
This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model.
Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56-0.69) and DME at 0.86 (IQR 0.73-1.00). After adjusting for age, sex, dose (mg/m), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03-1.65.
Early MTX elimination t measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.
大剂量甲氨蝶呤（HDMTX）的使用可能会受到急性肾损伤（AKI）的限制。早期 AKI 的检测对于防止进一步的肾损伤和不可逆的毒性至关重要。本研究旨在确定 MTX 的早期消除模式是否可作为 HDMTX 治疗中 AKI 的生物标志物。
这项回顾性队列研究包括两个收集 MTX 输注完成后 16 小时内至少 2 个 MTX 水平的地点。早期水平被标记，MTX 消除半衰期（t）是从三个早期时间段中的两个组合计算出来的。对于 AKI 和延迟甲氨蝶呤消除（DME），对每个消除 t（生物标志物）绘制接受者操作特征（ROC）曲线；ROC 曲线下面积（AUC）最高的生物标志物在多变量逻辑回归模型中进行了测试。
对 169 名接受了 556 次 HDMTX 治疗的患者的数据进行了分析。ROC 分析显示，从第二和第三时间段计算出的 MTX 消除 t 对 AKI 的 AUC 最高为 0.62（四分位距 [IQR] 0.56-0.69），对 DME 的 AUC 最高为 0.86（IQR 0.73-1.00）。在校正年龄、性别、剂量（mg/m）、输注时间、HDMTX 疗程和基线估算肾小球滤过率后，AKI 的 OR 为 1.29，95%置信区间为 1.03-1.65，仍具有统计学意义。
在输注完成后 16 小时内测量的早期 MTX 消除 t 与 AKI 的发生显著相关，可作为早期清除生物标志物，可识别受益于增加水化、增强甲酰四氢叶酸解救和葡萄糖醛酸酶治疗的患者。
