Role of molecular adsorbent recirculating system in methotrexate-induced acute liver failure: a case report and literature review

Abstract

We describe the case of a 14-year-old girl with osteosarcoma who was treated with high-dose methotrexate (12 g/m²). Twenty-four hours after the infusion, her plasma methotrexate concentration was elevated at 937 μmol/L (normal < 10 µmol/L). She exhibited severe signs of methotrexate toxicity, including encephalopathy, acute liver failure (ALF), and acute kidney injury. In this case report, we highlight the severe and rare adverse effects secondary to methotrexate administration and the efficacity of molecular adsorbent recirculating system and continuous venovenous hemodiafiltration to recover from multiple organ failure.

Keywords: acute kidney injury; acute liver failure; case report; extracorporeal treatment; methotrexate toxicity.

Figure 1

Time course of methotrexate and factor V levels according to extracorporeal therapies with MARS and CRRT.

Figure 2

Mechanism of action of glucarpidase and leucovorin in methotrexate toxicity. Methotrexate and leucovorin enter the cell via the RFC receptor and through passive diffusion in cases of high doses. MTX inhibits folate-dependent enzymes, including DHFR, thereby reducing purine production. This leads to a decrease in intracellular folate and inhibition of DNA synthesis. Leucovorin is essential for restoring sufficient intracellular folate levels. Glucarpidase rapidly reduces methotrexate levels by cleaving it into two inactive metabolites (DAMPA and glutamic acid), both of which are eliminated by the liver rather than the kidneys. Glucarpidase also inactivates leucovorin (5-FP and glutamic acid). 5FP, 5-formylpteroate; DAMPA, 4-deoxy-4-amino-N10-methylpteroic acid; DHFR, dihydrofolate reductase; GLU, glutamate; LV, leucovorin; MTX, methotrexate; RFC, reduced folate carrier; THE, tetrahydrofolate.