Crystalline Nephropathy With High-Dose Methotrexate in a Patient With Primary CNS Lymphoma: A Case Report

Methotrexate (MTX) is a folate antimetabolite used in the treatment of several malignancies and rheumatologic diseases. It is metabolized in the liver and excreted via the kidneys. Several adverse effects of MTX have been noted, including bone marrow suppression, mucositis, and hepatic and renal dysfunction. Close monitoring of drug levels, concurrent leucovorin administration, and urinary alkalization with aggressive hydration are some steps taken to prevent these unfavorable outcomes. We describe a case of a patient with primary CNS lymphoma undergoing chemotherapy with high-dose methotrexate (HD-MTX) who developed methotrexate-induced crystalline nephropathy despite preventative measures. Birefringent needle-shaped crystals were demonstrated under polarized light in the urine sample in the setting of acute kidney injury (AKI). The slow decay curve of MTX causing renal and hepatic dysfunction was an indication to start glucarpidase, and a subsequent rapid decline in MTX levels with improvement in AKI was observed. Methotrexate-induced crystalline nephropathy results from damage to the renal tubules, which in most cases is reversible. Patients with a slow decline in MTX levels may be candidates for treatment with glucarpidase, a recombinant form of carboxypeptidase G2, to allow for rapid MTX breakdown and clearance. Hemodialysis is another available treatment option for patients who develop these adverse effects.