Serum Methotrexate Level Predicts Acute Kidney Injury After High-Dose Methotrexate: A Case Report and Single-Center Experience

Background: 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. Methods: 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. Results: 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. Conclusion: 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.