Chronic Ifosfamide toxicity: kidney pathology and pathophysiology

Am J Kidney Dis. 2014 May;63(5):843-50. doi: 10.1053/j.ajkd.2013.11.028. Epub 2014 Feb 8.

Abstract

Ifosfamide is a nitrogen mustard alkylating agent used as both a first-line and a salvage chemotherapeutic agent in the treatment of testicular germ cell tumors, various sarcomas, carcinomas, and some lymphomas. A well-known complication of ifosfamide therapy is transient acute kidney injury. However, in a minority of patients, the reduction in kidney function is progressive and permanent, sometimes occurring long after exposure to ifosfamide. Scattered reports have described the pathologic findings in kidneys permanently affected by ifosfamide toxicity. We present the findings of an illustrative case and review the pathology and molecular mechanisms of long-term ifosfamide toxicity with implications for personalized medicine.

Keywords: Ifosfamide; chemotherapy-related injury; chronic kidney injury; drug toxicity; tubular toxicity.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Biopsy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Hodgkin Disease / drug therapy*
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects*
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy
  • Male
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / complications
  • Nephritis, Interstitial / pathology
  • Renal Dialysis
  • Time Factors
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Ifosfamide