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Kidney Week

Abstract: FR-PO018

Use of Glucarpidase in AKI from Methotrexate Toxicity and Delayed Methotrexate Clearance from Levetiracetam

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Stevens, Jacob, Columbia University, New York, New York, United States
  • Bomback, Andrew S., Columbia University, New York, New York, United States
Background

Methotrexate (MTX) is the backbone of many chemotherapeutic regimens, and the management of subsequent toxicity from delayed elimination is challenging. We describe a case of MTX toxicity and delayed MTX elimination and demonstrate the successful use of glucarpidase, a recombinant bacterial enzyme carboxypeptidease G2 that rapidly metabolizes MTX into glutamate and the inactive 2,4-diamino-N-methylpteroic acid.

Methods

A 67-year-old woman with hypothyroidism and CKD-3 presented with a 2-week history of progressive right hemiparesis. A R-thalamic lesion with vasogenic edema was found on imaging and dexamethasone and levetiracetam were started. A brain biopsy showed diffuse large B-cell lymphoma and temozolomide 150mg/m2, rituximab 500mg/m2, and high dose MTX (4271mg/m2 adjusted as a ~50% reduction based on a 24h CrCl of 47mL/min) were initiated, with leucovorin (LV) rescue 50mg q6h initiated at 24h. She developed delayed early MTX elimination and acute kidney injury (AKI) attributed to MTX crystal nephropathy despite urinary alkalinization (urine pH 8.0-9.0). She was supported with LV and isotonic bicarbonate with furosemide; despite these measures her MTX level remained elevated at 80µmol/L at 48h and a single dose of glucarpidase (3600units, 50units/kg) was given 53h after MTX exposure (LV held for 2h before and after) resulting in a rapid and precipitous fall in her MTX levels. She developed a mild transaminitis but no mucositis or severe myelosuppression. Her Cr peaked 10 days after MTX exposure, and returned to baseline before discharge.

Conclusion

This case of delayed early MTX elimination and AKI illustrates the importance of dose adjustment in the setting of co-administration of MTX and levetiracetam, which has been reported to delay MTX clearance, and highlights the successful use of glucarpidase for rapid metabolism of MTX in challenging cases when levels remain toxic despite LV and IVF supportive management.