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High-Dose Methotrexate Nephrotoxicity
Jaya Kala1, Scott C Howard2,3,4
1Division of Nephrology, Department of Internal Medicine, University of Texas Health Science Center-McGovern Medical School, Houston, Texas, USA, jaya.kala@uth.tmc.edu.
Background:
Methotrexate (MTX) is an antimetabolite anticancer agent that has been used at doses ranging from 20 mg/m2 of body surface area to 33,000 mg/m2. High-dose methotrexate (HDMTX), defined as doses higher than 500 mg/m2, is used to treat acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, brain cancers, leptomeningeal spread of carcinomas, and other cancers. Depending on the dose and other factors, acute kidney injury occurs in 2%-39% of HDMTX courses and severe (Acute Kidney Injury Network grade 2 or higher) nephrotoxicity in approximately 2%, though incidence varies widely. Prompt recognition and treatment of delayed MTX elimination and renal dysfunction which includes increased hydration, high-dose leucovorin, and sometimes glucarpidase, is crucial to prevent life-threatening toxicities such as myelosuppression, mucositis, renal failure, and dermatitis.
Summary:
In this article, we emphasize the importance of MTX pharmacokinetics and pharmacodynamics, highlight the cellular mechanisms of MTX anticancer activity, review the pathophysiology of MTX-induced renal injury, and explore strategies to prevent and manage MTX nephrotoxicity.
Key Messages:
Prompt recognition and effective treatment of renal and non-renal toxicities of HDMTX can improve outcomes, cancer prognosis, and survival.
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