Identifying risk factors for methotrexate-induced acute kidney injury despite full prevention in patients with primary central nervous system lymphoma

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-06-06 DOI:10.1016/j.taap.2025.117436

Wen-Ying Lin , Chun-Kuang Tsai , Chiu-Mei Yeh , Chia-Jen Liu

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引用次数: 0

Abstract

Background

Primary central nervous system lymphoma (PCNSL) accounts for 3 % of all brain tumors worldwide and high-dose methotrexate (HD-MTX) is used as the frontline chemotherapy. Given the renal excretion of methotrexate, we aimed to identify risk factors for HD-MTX–induced acute kidney injury (AKI) in patients with PCNSL. A comprehensive retrospective cohort study was conducted on newly diagnosed PCNSL patients who received HD-MTX chemotherapy.

Methods

Baseline characteristics, comorbidities, and laboratory data were collected at diagnosis and prior to each chemotherapy cycle. Serum methotrexate levels were measured at 24–48, 48–72, and 72–96 h post-infusion. Generalized estimating equations were used to identify risk factors for AKI. Among 146 patients with PCNSL, 108 received HD-MTX-based regimens, comprising 576 treatment cycles.

Results

Univariate analysis revealed that male gender, serum MTX levels ≥2 μmol/L at 48–72 h post-infusion, fluid accumulation in third spaces, low serum albumin, elevated blood urea nitrogen (BUN), and serum creatinine ≥2.0 mg/dL were all associated with increased AKI risk. In multivariate analysis, serum MTX levels ≥2 μmol/L and fluid accumulation in third spaces remained significant risk factors for AKI. Notably, none of the comorbidities were associated with the incidence of AKI.

Conclusions

These findings indicate that third-space fluid accumulation and elevated serum methotrexate levels at 48–72 h post-infusion are significant independent predictors of AKI in PCNSL patients receiving HD-MTX. We also developed a clinically applicable risk scoring system with strong predictive performance to support early identification and management of high-risk patients.

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原发性中枢神经系统淋巴瘤患者甲氨蝶呤诱导的急性肾损伤的危险因素识别，尽管完全预防。

背景：原发性中枢神经系统淋巴瘤（PCNSL）占全球所有脑肿瘤的3 %，高剂量甲氨蝶呤（HD-MTX）被用作一线化疗。考虑到甲氨蝶呤的肾脏排泄，我们旨在确定hd - mtx诱导的PCNSL患者急性肾损伤（AKI）的危险因素。我们对新诊断的PCNSL患者接受HD-MTX化疗进行了全面的回顾性队列研究。方法：在诊断时和每个化疗周期前收集基线特征、合并症和实验室数据。注射后24- 48,48 -72和72-96 h测定血清甲氨蝶呤水平。采用广义估计方程确定AKI的危险因素。在146例PCNSL患者中，108例接受了基于hd - mtx的方案，包括576个治疗周期。结果：单因素分析显示，男性、输注后48 ~ 72 h血清MTX水平≥2 μmol/L、第三空间积液、血清白蛋白低、血尿素氮（BUN）升高、血清肌酐≥2.0 mg/dL与AKI风险增加相关。在多因素分析中，血清MTX水平≥2 μmol/L和第三空间积液仍然是AKI的重要危险因素。值得注意的是，没有任何合并症与AKI的发生率相关。结论：这些研究结果表明，第三空间液体积聚和注射后48-72 h血清甲氨蝶呤水平升高是接受HD-MTX的PCNSL患者AKI的重要独立预测因素。我们还开发了临床适用的风险评分系统，具有较强的预测性能，支持早期识别和管理高危患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.