Acute kidney injury (AKI) is a serious complication following high-dose methotrexate (HD-MTX) treatment, despite established preventive measures. This study presents a case report and a retrospective review of patients treated with HD-MTX, aiming to identify risk factors for AKI and propose a modified treatment protocol. We report a case of a 43-year-old man with diffuse large B-cell lymphoma who developed severe AKI after HD-MTX therapy. Additionally, a retrospective review of 70 patients receiving HD-MTX at our institution was conducted to identify predictors of AKI. Serum methotrexate levels were analyzed to determine their significance in predicting AKI. The index patient developed methotrexate intoxication and severe AKI despite receiving standard prophylactic measures, requiring temporary hemodialysis. The retrospective review identified serum methotrexate levels as a significant predictor of AKI (OR 11.84, 95% CI: 2.62-53.53, p = 0.001). Higher initial serum methotrexate levels correlated with the development of AKI. Timely measurement of serum methotrexate levels is crucial in managing and preventing AKI in patients undergoing HD-MTX therapy. Based on our findings, we propose a modified HD-MTX treatment protocol to reduce the incidence of AKI. This includes earlier serum methotrexate level monitoring and adjustments in urine alkalization and leucovorin dosing strategies.
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