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Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose

Torben Stamm Mikkelsen1, Aissata Diop Mamoudou, Ruta Tuckuviene

  • 1Department of Pediatric Oncology, Aarhus University Hospital, Aarhus, Denmark.

Pediatric Blood & Cancer
|September 17, 2013
PubMed

Insights

Extending prehydration for high-dose methotrexate (HDMTX) infusions beyond 4 hours does not reduce renal toxicity or affect methotrexate clearance in children with ALL. This finding impacts supportive care protocols for pediatric cancer patients receiving HDMTX.

Area of Science:

  • Pediatric Oncology
  • Pharmacology
  • Nephrology

Background:

  • Alkalized hydration is standard supportive care to prevent renal toxicity from high-dose methotrexate (HDMTX).
  • Current protocols in pediatric acute lymphoblastic leukemia (ALL) typically initiate hydration 4 hours before HDMTX infusion.
  • The study investigated if extending this prehydration period would mitigate MTX-induced renal toxicity.

Purpose of the Study:

  • To determine if extending prehydration time from 4 to 12 hours reduces renal toxicity associated with HDMTX infusions in pediatric patients.
  • To assess the impact of prehydration duration on systemic methotrexate clearance.

Main Methods:

  • A randomized cross-over study design was employed in children with ALL and non-Hodgkin lymphoma receiving HDMTX (5 or 8 g/m²).
  • Patients alternated between 4 and 12 hours of intravenous prehydration before HDMTX infusions.
  • Renal toxicity was defined as a 50% increase in plasma creatinine; plasma MTX concentrations were monitored.

Main Results:

  • Prehydration duration had no significant effect on MTX-induced renal toxicity.
  • Renal toxicity rates were 18.5% for HDMTX 5 g/m² and 40.0% for HDMTX 8 g/m² infusions, irrespective of prehydration time.
  • Systemic MTX clearance was not influenced by the duration of prehydration.

Conclusions:

  • Extending prehydration for HDMTX infusions beyond 4 hours does not decrease the incidence of renal toxicity.
  • Prehydration duration does not impact the systemic clearance of MTX.
  • Current 4-hour prehydration protocols are adequate for preventing renal toxicity and ensuring proper MTX clearance in pediatric patients.
Abstract

Keywords:
drug clearancehydrationmethotrexatenephrotoxicitypharmacokinetics

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