Faguer Stanislas, Medrano Chloé, Tavitian Suzanne, Oberic Lucie
Department of Nephrology and Organ Transplantation, French Intensive Care Renal Network (F.I.R.N), University Hospital of Toulouse, Toulouse, France.
Faculty of Health, University of Toulouse-3, Toulouse, France.
Kidney360. 2025 Mar 1;6(3):476-481. doi: 10.34067/KID.0000000725. Epub 2025 Jan 31.
AKI is a rare but life-threatening complication of the administration of methotrexate (MTX) at high doses (≥1 g/m 2 ) for the treatment of solid or hematological malignancies. MTX overexposure can lead to MTX-AKI and subsequent higher risk of extrakidney toxicities, morbidity, and mortality. MTX-AKI can also lead to secondary CKD requiring a reduced dose or contraindication for subsequent MTX infusions, thus worsening the cancer-related prognosis. Treatment of MTX-AKI is mainly preventive, combining alkaline hyperhydration, withdrawal of all nephrotoxic agents and drugs that modulate the metabolism of MTX, metabolic salvage using leucovorin (folinic acid), and close monitoring of serum MTX and creatinine concentrations. Glucarpidase (carboxypeptidase-G2), a recombinant bacterial enzyme that hydrolyzes MTX into two noncytotoxic metabolites, should be considered for patients with MTX overexposure to prevent and lessen AKI and other potential toxicities. This article provides a comprehensive review of MTX metabolism, mechanisms and prevention of MTX-AKI, and its management.
急性肾损伤（AKI）是高剂量（≥1 g/m²）甲氨蝶呤（MTX）用于治疗实体瘤或血液系统恶性肿瘤时罕见但危及生命的并发症。MTX暴露过量可导致MTX相关性急性肾损伤（MTX-AKI）以及随后发生肾外毒性、发病率和死亡率升高的风险。MTX-AKI还可导致继发性慢性肾脏病（CKD），需要减少后续MTX输注的剂量或禁忌使用，从而使癌症相关预后恶化。MTX-AKI的治疗主要是预防性的，包括碱性水化、停用所有肾毒性药物以及调节MTX代谢的药物、使用亚叶酸钙进行代谢救援以及密切监测血清MTX和肌酐浓度。对于MTX暴露过量的患者，应考虑使用葡糖醛酸酶（羧肽酶-G2），这是一种重组细菌酶，可将MTX水解为两种无细胞毒性的代谢产物，以预防和减轻AKI及其他潜在毒性。本文对MTX代谢、MTX-AKI的机制和预防及其管理进行了全面综述。
