Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Cancer. 2015 Nov 1;121(21):3894-904. doi: 10.1002/cncr.29587. Epub 2015 Jul 28.

Abstract

Background: Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic-phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.

Methods: Four hundred sixty-eight newly diagnosed CP CML patients treated with TKIs were analyzed. The molecular and cytogenetic response data, creatinine, and glomerular filtration rate (GFR) were followed from the start of therapy to the last follow-up (median, 52 months). GFR was estimated with the Modification of Diet in Renal Disease equation.

Results: Nineteen patients (4%) had TKI-associated AKI. Imatinib was associated with a higher incidence of AKI in comparison with dasatinib and nilotinib (P = .014). Fifty-eight patients (14%) developed CKD while they were receiving a TKI; 49 of these patients (84%) did so while they were being treated with imatinib (P < .001). Besides imatinib, age, a history of hypertension, and diabetes mellitus were also associated with the development of CKD. In patients with no CKD at the baseline, imatinib was shown to reduce GFR over time. Interestingly, imatinib did not cause a significant decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led with the most significant increase (P < .001). AKI or CKD had no significant impact on overall cytogenetic and molecular response rates or survival.

Conclusions: The administration of TKIs may be safe in the setting of CKD in CP CML patients, but close monitoring is still warranted.

Keywords: chronic myeloid leukemia (CML); dasatinib; glomerular filtration rate changes; imatinib; kidney injury; nilotinib; outcome; tyrosine kinase inhibitor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / epidemiology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Creatinine / metabolism
  • Dasatinib / adverse effects
  • Dasatinib / pharmacology
  • Dasatinib / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use
  • Incidence
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / physiopathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / epidemiology
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Creatinine
  • Protein-Tyrosine Kinases
  • nilotinib
  • Dasatinib