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Methotrexate Crystal Nephropathy — ESENeph MCQ

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HardAcute Kidney InjuryMethotrexate Crystal NephropathyESENeph

A 55-year-old woman develops AKI while on Methotrexate for rheumatoid arthritis. Her creatinine rises from 80 to 350 umol/L. Methotrexate level is markedly elevated. Urine microscopy shows crystalluria. What is the mechanism and treatment?

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Correct answer: E — Intratubular Methotrexate crystal precipitation in acidic urine – IV fluids, urinary alkalinisation, and Glucarpidase (carboxypeptidase G2) for severe toxicity

High-dose Methotrexate (and even standard doses in CKD patients with impaired clearance) can cause AKI through intratubular crystal precipitation, particularly in acidic urine. Treatment includes aggressive IV hydration, urinary alkalinisation (IV sodium bicarbonate targeting urine pH >7), and Glucarpidase (carboxypeptidase G2) for life-threatening toxicity – Glucarpidase rapidly cleaves Methotrexate to inactive metabolites. Leucovorin rescue should also be given.

Reference: NICE – Methotrexate Safety; Howard et al 2016 – Glucarpidase for MTX Toxicity