Continuous veno-venous hemodiafiltration in methotrexate intoxication

Methotrexate is a highly nephro- and hepatotoxic drug used in osteosarcoma treatment protocols, in children and adults. High dose methotrexate therapy may lead to kidney injury and decrease of methotrexate clearance, followed by an increase of its serum concentration. As a result, systemic intoxication may develop. Prophylaxis based on intensive fluid therapy and urine alkalization may not be sufficient to prevent the formation of methotrexate crystals in kidney tubules. THE AIM of the study was to present three cases of methotrexate intoxication treated with continuous veno-venous hemodiafiltration.

Three children aged 9-16 years old with tibial or fibular osteosarcoma were admitted to the Nephrology Department due to severe methotrexate intoxication. All children presented with multiorgan injury, including liver, kidney, gastrointestinal tract and bone marrow impairment. Methotrexate concentration, 24 hours after drug administration, was 660-1238 µmol/L. Although intensive fluid therapy, urine alkalisation and administration of high doses of folinic acid (leucovorin), methotrexate serum concentration remained toxic. Effective reduction of methotrexate concentration (<1.5 μmol/L) was achieved 24-156 hours after CVVHDF initiation. Kidney and liver function recovered completely in all of the patients.

Continuous veno-venous hemodiafiltration is an effective supportive method in methotrexate elimination in patients with severe intoxication.