AUTHOR=Tome Ana Carolina Nakamura , Santos Karise Fernades , Lima Emerson Quintino , Ramalho Rodrigo Jose TITLE=High-flux hemodialysis as rescue therapy for high-dose methotrexate toxicity: case series and clinical insights JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1495705 DOI=10.3389/fmed.2025.1495705 ISSN=2296-858X ABSTRACT=High-dose methotrexate (HD-MTX) toxicity represents a significant clinical challenge in oncology, commonly resulting in acute kidney injury (AKI), myelosuppression, and potentially life-threatening multiorgan failure. This case series describes three patients treated at Hospital de Base in São José do Rio Preto, Brazil, who developed HD-MTX-induced AKI following the administration of chemotherapy. Two patients had hematologic malignancies and one had osteosarcoma. All received conventional rescue therapies, including leucovorin and aggressive hydration, but demonstrated persistent elevation of serum methotrexate levels, necessitating the initiation of high-flux hemodialysis (HF-HD). The mean number of HF-HD sessions required was 5.3 ± 2.5, and the mean relative reduction in serum methotrexate concentration was 44.5 ± 19.1%. These findings suggest that HF-HD is an effective therapeutic option for HD-MTX toxicity management in settings where glucarpidase is not readily available, although repeated sessions may be required due to the observed rebound in serum methotrexate levels.