Acute kidney injury after high-dose methotrexate application – case report

Methotrexate, administered in high doses, is utilized in the treatment of a range of childhood cancers. Despite the implementation of routine supportive measures, including intensive hydration, urine alkalinization, and antidote therapy, nephrotoxicity remains a significant problem. The literature suggests a range of frequencies from 1.8% to 36%, depending on the diagnostic method employed. The primary pathogenetic mechanism of its occurrence is the precipitation of methotrexate and its metabolites in the renal tubules, clinically manifesting as crystalline nephropathy, which leads to delayed excretion of the medication. The risk factors, long-term renal prognosis, and safety of re-administration of high-dose methotrexate after an episode of acute kidney injury remain unclear. In the event of nephrotoxicity, restriction of its further use and substitution with another cytostatic drug are often considered. The following clinical case is presented: a 13-year-old girl with osteosarcoma was administered high-dose methotrexate, resulting in fourth-degree acute kidney injury. This necessitated a renal replacement therapy. Given its pivotal role in osteosarcoma treatment, subsequent courses were planned with gradually increasing doses. Four additional courses of high-dose methotrexate were administered at doses of 3 g/m2, 8 g/m2, and 12 g/m2, until the maximum tolerable dose of 20 grams was reached. These courses were well tolerated, with no evidence of toxicity, and the medication was eliminated in a timely manner.