Urine methotrexate crystals in the diagnosis of methotrexate induced acute kidney injury: Case report

High-dose Methotrexate (MTX) is commonly used in the treatment of hematologic malignancies but can be complicated by acute kidney injury (AKI), most often due to MTX-induced crystal nephropathy. Direct visualization of MTX crystals on urine microscopy is rarely reported and likely underrecognized. We describe a case of an elderly woman with diffuse large B-cell lymphoma (DLBCL) and central nervous system metastasis who developed AKI after receiving high-dose MTX as part of the MTX, Cytarabine, Thiotepa, Rituximab (MATRIX) chemotherapy regimen. This was followed by significant supratherapeutic levels of MTX with progressive decline in kidney function reflecting AKI, which was attributed to intratubular crystal precipitation. Management consisted of high dose leucovorin, aggressive intravenous hydration, and urinary alkalinization with sodium bicarbonate and acetazolamide, resulting in gradual MTX clearance. The diagnosis was supported by delayed drug clearance, worsening kidney function, and the direct visualization of MTX crystals on urine microscopy, a finding that makes this case unique.