Case Presentation: A 75-year-old female presented to the emergency department with a history of multiple falls. Her physical exam was unremarkable. A computerized tomographic scan of the head and magnetic resonance imaging (MRI) with the contrast of brain showed frontoparietal mass with metastatic brain lesions. Right frontal craniotomy with tumor resection was done and biopsy showed diffuse large B cell lymphoma. Postoperatively she developed bilateral lower extremity motor weakness (2/5). She was started on HDMTX and Rituximab with improvement in lower extremity weakness. After 2 days of therapy, she developed oliguric AKI with progressively rising serum creatinine (Cr) from baseline 0.9 mg/dl to 3.2mg/dl. Renal ultrasound and urinalysis were unremarkable. Serum MTX levels 24 hours and 48 hours post-therapy were 310 umol/L and 427 umol/L, respectively. MTX induced AKI was not responsive to leucovorin rescue therapy and IVF hydration with isotonic sodium bicarbonate so she was emergently dialyzed with high flux dialyzer, with a slight decrease in MTX levels from 427 to 293 after a 2-hour session. Glucarpidase administration was delayed until the fourth day of HDMTX due to unavailability. After 1 dose of glucarpidase MTX dropped significantly from 293 to 71.9. Urine output improved, however, she continued to require intermittent hemodialysis due to poor solute clearance. The patient eventually opted for comfort care because of multiple comorbidities.
Discussion: High-dose methotrexate (HDMTX, >1 g/m2) is associated with acute kidney injury (AKI)1. MTX induced AKI occurs by precipitation and direct toxic effect on renal tubules. It can be prevented by hydration with alkaline intravenous fluids (IVF) and leucovorin. Glucarpidase is used for the treatment of toxic methotrexate plasma concentrations (>1 umol/L) in patients with delayed clearance due to renal impairment. MTX induced nephrotoxicity can develop even with the recommended protocols of IVF hydration and urine alkalization, along with leucovorin rescue. Our case highlights the importance of early treatment of MTX toxicity with glucarpidase along with extracorporeal methods to remove the drug. Centers using HDMTX should have a protocol for ready availability of charcoal hemofilter and glucarpidase. Regular hemodialysis is not optimally effective for HDMTX toxicity.
Conclusions: Delay in glucarpidase administration can result in worsening irreversible renal and extrarenal toxicities. So glucarpidase administration should optimally start within 48-60 hours of HDMTX initiation, with any delay being bridged with charcoal hemofilter.