Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia

Leuk Res. 2009 Feb;33(2):344-7. doi: 10.1016/j.leukres.2008.07.029. Epub 2008 Oct 2.

Abstract

Tyrosine kinase inhibitors (TKIs) directed against the Bcr-Abl kinase have revolutionized the treatment of chronic myelogenous leukemia (CML). Relatively little is known regarding the effects of these agents on the kidney. Clinically, there have been a handful of reports associating imatinib with acute renal failure. Preclinical reports indicate that imatinib inhibits signaling pathways which may play a role in renal injury. We report the case of a patient with imatinib-resistant CML who developed renal failure after being placed on dasatinib. When she later became resistant to dasatinib she was switched to nilotinib. Shortly thereafter, she became dialysis-independent. Second-generation Bcr-Abl TKIs may influence renal function based on differential inhibition of related tyrosine kinases.

Publication types

  • Case Reports

MeSH terms

  • Benzamides
  • Dasatinib
  • Drug Resistance, Neoplasm
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Middle Aged
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Renal Dialysis
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / therapy
  • Thiazoles / adverse effects

Substances

  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Dasatinib