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Methotrexate Nephrotoxicity — SCE Medical Oncology MCQ

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ModerateOncological EmergenciesMethotrexate NephrotoxicitySCE Medical Oncology

A 55-year-old man receiving high-dose methotrexate for CNS lymphoma develops acute renal failure. Methotrexate level is markedly elevated at 24 hours. What is the mechanism of methotrexate nephrotoxicity?

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Correct answer: D — Methotrexate and its metabolites (7-OH-MTX and DAMPA) precipitate in renal tubules at acidic pH — prevention requires aggressive alkaline hydration (urine pH ≥7.0) and leucovorin rescue

High-dose methotrexate (≥1 g/m²) causes renal toxicity through crystallisation of methotrexate and its metabolites (particularly 7-OH-MTX) in renal tubules, especially at acidic urine pH. Prevention requires: aggressive IV hydration (3 L/m²/day), urinary alkalinisation (NaHCO3 to maintain urine pH ≥7.0), leucovorin rescue (starting 24h post-MTX), and serial MTX level monitoring. Treatment of established toxicity includes: increased IV fluids, urinary alkalinisation, continued leucovorin (until MTX <0.05 µmol/L), and consideration of glucarpidase (carboxypeptidase G2) for severe toxicity.

Reference: BNF Methotrexate; ESMO Supportive Care; NICE NG99