Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia.
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.
Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Sarah A
SA
Holstein
John B
JB
Stokes
Raymond J
RJ
Hohl
D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications* / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000628:therapy; D013844:Thiazoles / Q000009:adverse effects
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib