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Abstract: FR-PO187

Methotrexate Deja Vu: The Solution Is in the Volume!

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Ayub, Fatima, University of Arkansas System, Little Rock, Arkansas, United States
  • Bashtawi, Yazan Ali, University of Arkansas System, Little Rock, Arkansas, United States
  • Karakala, Nithin, University of Arkansas System, Little Rock, Arkansas, United States
Introduction

Methotrexate (MTX) has a broad range of antitumor activity. Acute methotrexate toxicity rarely presents as a renal failure. We, hereby present a case of MTX-induced acute renal failure with evidence of MTX-induced tubular injury.

Case Description

74 years old male with a past medical history of hypertension, presented to the emergency department with complaints of altered mentation and recurrent falls. He had a 3-month history of cognitive decline, unsteady gait, and mechanical falls. Over the course of 3 days prior to the presentation, his wife noticed him to be drowsier.
Brain imaging showed a lesion in the right frontal lobe followed by a biopsy of the lesion that demonstrated diffuse large B cell lymphoma. He was subsequently started on a chemotherapy regimen with MTX. Following the third dose, the patient developed acute hypoxic respiratory failure with acute kidney injury. Serum creatinine of 4.7 mg/dL (Baseline: 0.9 mg/dl) and a serum MTX level of 107 uMol/L was consistent with MTX toxicity. Urine microscopy revealed MTX crystals. Chemotherapy was discontinued and he underwent emergent hemodialysis (HD) for the management of MTX toxicity. Serum MTX levels after the first dialysis treatment was 74 uMol/L which increased back to 87 uMol/L within 24 hours of the first HD session. He underwent three daily sessions of HD due to the continuous rebound of MTX levels after each session. After his fourth dialysis treatment MTX level was 2.4 uMol/L.

Discussion

MTX-induced renal failure is a medical emergency because methotrexate is mainly eliminated by the kidneys. Renal damage is due to the precipitation of methotrexate in the tubules leading to tubular injury. Drug precipitation can often be prevented by hydration and alkalization of the urine. It is important to note that the volume of distribution of MTX is 1L/Kg. There is a high risk of rebound in serum levels of substances/drugs that have a large volume of distribution after short dialysis sessions. It is extremely important to understand the pharmacokinetics like volume of distribution, and protein binding to optimize the dialysis treatment.