Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hematol Oncol. 2020 Oct;38(4):584-588. doi: 10.1002/hon.2759. Epub 2020 Jun 24.
High dose methotrexate (HDMTX)-induced acute kidney injury (AKI) is a well-known adverse event in hemato-oncology patients. Our purpose was to define factors and setup cut-offs that may help better identify patients at-risk for developing AKI following HDMTX. All consecutive patients who received MTX dose ≥1 g were retrospectively reviewed. We compared patients with or without renal toxicity. We used a logistic regression model to define baseline variables associated with AKI. Overall survival (OS) was estimated by the Kaplan-Meier method employing log-rank test. Between 2012 and 2017, 160 patients were included with a total of 265 courses. Indications included: primary central nervous system (CNS) lymphoma, CNS prophylaxis in other lymphoma types, acute lymphatic leukemia and others. Median age at diagnosis was 58 years (range, 18-84), 54% were males, median MTX dose was 1941 mg/m (range, 743-5442) and AKI developed in 9% of drug administrations (n = 24). In univariate analysis: age > 40, LDH > 380 units/L, eGFR < 112 mL/min, albumin <3.6 mg/dL at baseline and Charlson comorbidity index (CCI) were associated with AKI. In multivariable analysis, only LDH > 380 units/L (OR = 4.1, 95% confidence interval [CI] 1.04-20.9, P = .04) and albumin levels <3.6 g/dL (OR = 4.17, 95% CI 1.04-6.5, P = .04) remained significant. In patients with AKI, median drug elimination was longer (8 days vs 5 days). In 80% of cases, the creatinine levels returned to normal within 1 month. Yet, the median survival of patients who developed AKI was 37 months, compared to 145 months in patients without AKI (Log rank = 0.015). In conclusion, LDH > 380 units/L and albumin <3.6 g/dL were the strongest factors associated with AKI in patients receiving HDMTX. Although the rise in creatinine levels was almost uniformly reversible, AKI was associated with increased mortality rates.
高剂量甲氨蝶呤（HDMTX）诱导的急性肾损伤（AKI）是血液肿瘤患者中已知的不良事件。我们的目的是确定可能有助于更好地识别接受 HDMTX 后发生 AKI 风险的患者的因素和设置截止值。回顾性分析了所有接受 MTX 剂量≥1g 的连续患者。我们比较了有或没有肾毒性的患者。我们使用逻辑回归模型来定义与 AKI 相关的基线变量。通过对数秩检验的 Kaplan-Meier 方法估计总生存率（OS）。2012 年至 2017 年间，共纳入 160 例患者，共 265 例。适应证包括：原发性中枢神经系统（CNS）淋巴瘤、其他淋巴瘤类型的 CNS 预防、急性淋巴细胞白血病等。中位诊断年龄为 58 岁（范围 18-84 岁），54%为男性，中位 MTX 剂量为 1941mg/m（范围 743-5442），9%的药物治疗中发生 AKI（n=24）。在单因素分析中：年龄>40 岁、LDH>380 单位/L、eGFR<112mL/min、基线时白蛋白<3.6mg/dL 和 Charlson 合并症指数（CCI）与 AKI 相关。在多变量分析中，仅 LDH>380 单位/L（OR=4.1，95%置信区间[CI]1.04-20.9，P=0.04）和白蛋白水平<3.6g/dL（OR=4.17，95%CI1.04-6.5，P=0.04）仍然具有显著性。在发生 AKI 的患者中，药物消除中位数更长（8 天 vs 5 天）。在 80%的病例中，肌酐水平在 1 个月内恢复正常。然而，发生 AKI 的患者的中位生存时间为 37 个月，而无 AKI 的患者为 145 个月（对数秩=0.015）。总之，在接受 HDMTX 的患者中，LDH>380 单位/L 和白蛋白<3.6g/dL 是与 AKI 最相关的最强因素。尽管肌酐水平升高几乎普遍是可逆的，但 AKI 与死亡率升高相关。
