High-Dose Methotrexate (HDMTX) Induced Nephrotoxicity: Glucarpidase or Dialysis?

Author Type(s)

Faculty, Resident/Fellow

Document Type

Abstract

Publication Date

2022

Journal Title

Journal of the American Society of Nephrology

Department

Medicine

Abstract

Introduction: HDMTX induced Acute Kidney Injury (AKI) can lead to delayed renal clearance of MTX causing life threatening toxicities. Treatment options include high-flux hemodialysis (HFHD) and Glucarpidase. We report a case of MTX induced AKI which was successfully treated with Glucarpidase. Case Description: 75 year old woman admitted with CNS lymphoma, planned for 6 cycles of HDMTX based chemotherapy. She received 3 cycles with no side effects. Urine pH and MTX levels were monitored with levels peaking at 2.2, 7.7and 7.5 umol/L with no AKI. During her 4th cycle, she was found to have AKI on day 5. Blood work showed BUN 23 mg/dL and creatinine (Cr) 1.46 mg/dL. She had been normotensive with no administration of nephrotoxic medications or contrast except HDMTX. MTX level was found to be 110.5 umol/L. She was started on hydration, sodium bicarbonate and leucovorin was increased. She received one dose of Glucarpidase 50 units/kgs, 52 hours after HDMTX infusion with decrease in MTX level to 21.7 umol/L. MTX levels were closely monitored and continued to downtrend. Urine pH levels were monitored to keep pH >7. Patient did not need further doses of Glucarpidase and decision was made to not initiate HD. She was discharged in renal recovery. Discussion: Routine monitoring of MTX levels can lead to early recognition of AKI. Glucarpidase is an enzyme that cleaves MTX into inactive metabolites providing an alternative route for elimination. Case reports describe successful treatment of AKI with its use in addition to leucovorin rescue, hyperhydration and urine alkalization. Our patient was treated successfully with the same regimen with absence of other MTX toxicities. In the above reports, there was no rebound in MTX levels after single dose Glucarpidase as seen in our patient also. Another treatment option is HFHD, but reports show that MTX levels rebound and require repeat sessions. Recently published guidelines recommend the use of Glucarpidase for HDMTX related AKI but MTX levels not corresponding to the algorithm is a limitation to its use. Despite this, we hypothesize that its use can help avoid HD. Randomized controlled trials are warranted to assess its efficacy on clinically relevant outcomes. Learning objectives Routine monitoring of MTX levels can lead to early recognition of AKI. Prompt intervention with Glucarpidase can successfully treat AKI with no rebound in MTX levels and eliminate the need for HD.

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