Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Eur J Clin Pharmacol. 2023 Jun;79(6):789-800. doi: 10.1007/s00228-023-03491-7. Epub 2023 Apr 15.
To assess the risk factors associated with high-dose methotrexate (HDMTX) (≥ 1 g/m) treatment-induced acute kidney injury (AKI).
Patients who received HDMTX from July 2014 to August 2019 in one medical center were enrolled. The patients' demographic, laboratory, and medication data were collected and compared between groups with or without AKI. Risk factors of HDMTX-induced AKI were explored using univariate and multivariate logistic regression analyses. Additionally, we searched and summarized previous studies to identify key correlates of AKI in a narrative review.
We enrolled 59 patients who had received 200 HDMTX courses. The incidence of HDMTX-induced nephrotoxicity was 9.5%. Multivariate logistic regression revealed that male sex (odds ratio [OR], 4.20; P = .037), and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 5.18; P = .016) were significantly associated with AKI. Diuretics with urinary acidification, such as loop diuretics, were also a key factor in AKI (OR, 4.91; P = .018). Furthermore, a forest plot identified 21 predictors from nine additional cohort studies showing correlations with the development of AKI.
Male sex, ACEIs/ARBs, and diuretics with urinary acidification are associated with AKI. Furthermore, laboratory data should be monitored to assess AKI risk before HDMTX therapy, especially in elderly patients with obesity, diabetes, or acute lymphoblastic leukemia.
评估与大剂量甲氨蝶呤（HDMTX）（≥1g/m）治疗相关的急性肾损伤（AKI）的危险因素。
纳入 2014 年 7 月至 2019 年 8 月在一家医疗中心接受 HDMTX 治疗的患者。收集患者的人口统计学、实验室和用药数据，并比较 AKI 组和非 AKI 组之间的差异。采用单因素和多因素 logistic 回归分析探讨 HDMTX 诱导 AKI 的危险因素。此外，我们还进行了文献检索和综述，以确定 AKI 的关键相关因素。
共纳入 59 例接受 200 例 HDMTX 疗程的患者。HDMTX 诱导的肾毒性发生率为 9.5%。多因素 logistic 回归分析显示，男性（优势比[OR]，4.20；P=0.037）和血管紧张素转换酶抑制剂（ACEIs）/血管紧张素受体阻滞剂（ARBs）（OR，5.18；P=0.016）与 AKI 显著相关。具有尿液酸化作用的利尿剂，如袢利尿剂，也是 AKI 的一个关键因素（OR，4.91；P=0.018）。此外，从另外 9 项队列研究中确定了一个森林图，其中 21 个预测因子与 AKI 的发生相关。
男性、ACEIs/ARBs 和具有尿液酸化作用的利尿剂与 AKI 相关。此外，在接受 HDMTX 治疗之前，应监测实验室数据以评估 AKI 风险，尤其是在肥胖、糖尿病或急性淋巴细胞白血病的老年患者中。
