High incidence of methotrexate associated renal toxicity in patients with lymphoma: a retrospective analysis

Leuk Lymphoma. 2014 Jun;55(6):1345-9. doi: 10.3109/10428194.2013.840780. Epub 2013 Nov 1.


High-dose methotrexate (HDMTX), defined by doses of methotrexate (MTX) ≥ 1 g/m(2), is a widely used regimen known to cause renal toxicity. The reported incidence of renal toxicity in patients with osteosarcoma is 1.8%, but the incidence in hematologic malignancies is not well characterized. In this retrospective study of 649 cycles of HDMTX in 194 patients, renal toxicity occurred in 9.1% of cycles in patients with lymphoma compared to 1.5% in patients with sarcoma. Older age, male sex, decreased baseline creatinine clearance (CrCl) and increased proton pump inhibitor use among the lymphoma population likely contributed to the observed difference. The incidence of renal toxicity was independent of the incidence of delayed MTX elimination, suggesting that kidney function is only one factor involved in MTX clearance. Renal toxicity prolonged the duration of hospitalization but severe renal insufficiency was uncommon. No significant impact on progression-free or overall survival was observed.

Keywords: High-dose methotrexate; lymphoma; renal toxicity.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Female
  • Hospital Mortality
  • Humans
  • Incidence
  • Length of Stay
  • Lymphoma / complications*
  • Lymphoma / drug therapy
  • Lymphoma / mortality
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Patient Outcome Assessment
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / epidemiology*
  • Retrospective Studies
  • Risk Factors


  • Antimetabolites, Antineoplastic
  • Methotrexate