Low-dose Methotrexate Toxicity in the Setting of Vancomycin-induced Acute Kidney Injury

Abstract

Methotrexate is a disease-modifying anti rheumatic drug (DMARD) that is often used in low dosages as the first line drug for rheumatoid arthritis patients. The chemotherapeutic agent works by inhibiting dihydrofolate reductase, and the primary route of clearance of the drug is via the kidneys. Kidney injury may delay this clearance and lead to toxic level accumulation of the drug- toxicity presenting as diarrhea, vomiting, mucositis, rash, transaminitis and myelosuppression. Antibiotics such as vancomycin may induce acute kidney injury (AKI) through various mechanisms include damage to the renal tubular epithelial cells. In this report, we describe a case in which an elderly female suffered AKI secondary to vancomycin induced nephrotoxicity. The AKI subsequently led to methotrexate accumulation and toxicity presenting as bleeding mouth ulcers, transaminitis and pancytopenia. The condition was managed with leucovorin rescue therapy and sodium bicarbonate to enhance methotrexate excretion. Renally dosing methotrexate in patients on other nephrotoxic drugs, and monitoring creatinine clearance are methods for preventing such a toxicity.