Glucarpidase Rescue After High-Dose Methotrexate in Osteosarcoma: A Case Report

Abstract Background Osteosarcoma is a rare primary malignant bone tumor for which high-dose methotrexate remains an important component of chemotherapy in selected patients. Acute kidney injury with markedly delayed methotrexate clearance is an uncommon but potentially life-threatening complication. Case presentation We report the clinical course and management of high-dose methotrexate–induced acute kidney injury requiring glucarpidase rescue in a 23-year-old white woman with localized osteosarcoma of the right distal femur. She received her first cycle of high-dose methotrexate (20 g over 4 hours) as part of neoadjuvant chemotherapy. Baseline serum creatinine was 0.50 mg/dL. Despite intravenous hydration, urinary alkalinization, and leucovorin rescue, she developed non-oliguric acute kidney injury within 24 hours, with serum creatinine increasing to 2.32 mg/dL and plasma methotrexate concentration reaching 148 µmol/L. At 48 hours, methotrexate concentration remained elevated at 25 µmol/L, with persistent renal dysfunction. Glucarpidase 5,000 U was administered intravenously, and leucovorin rescue was intensified. Methotrexate concentrations subsequently declined progressively, while renal function gradually recovered. The clinical course was complicated by grade 3 anemia requiring red blood cell transfusion, transient hypokalemia, and volume overload. The patient was discharged 11 days after high-dose methotrexate administration with preserved urine output and improving renal function. Serum creatinine decreased to 1.28 mg/dL two weeks after discharge and to 0.63 mg/dL one month later. Further high-dose methotrexate was discontinued, and neoadjuvant chemotherapy was continued with cisplatin and doxorubicin. Conclusions This case describes a serious complication of high-dose methotrexate treatment in a patient with a rare bone malignancy. It highlights the importance of close biochemical monitoring, early recognition of delayed methotrexate clearance, and timely glucarpidase administration in patients who develop acute kidney injury despite appropriate supportive measures.