Changes in estimated glomerular filtration rate in chronic myeloid leukemia patients treated front line with available TKIs and correlation with cardiovascular events

Ann Hematol. 2018 Oct;97(10):1803-1808. doi: 10.1007/s00277-018-3375-9. Epub 2018 May 27.

Abstract

We investigated the median estimated glomerular filtration rate (eGFR) changes in chronic myeloid leukemia (CML) patients treated front line with tyrosine kinase inhibitors (TKIs). A large cohort of 397 patients-320 treated front line with imatinib, 25 with dasatinib, and 53 with nilotinib-was retrospectively analyzed at a single institution. The eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation for all patients at baseline and then at 6 and 12 months, and at the last follow-up. Taking into account eGFR changes during the first year of treatment and excluding other possible cardiovascular risk factors, we considered also the percentage of cardiovascular events in patients with modifications of this single parameter. Imatinib induced a decrease in median eGFR (p = 0.01): 42 patients treated with imatinib had a cardiovascular event, related to modification of eGFR, in the absence of other cardiovascular risk factors. In patients treated with nilotinib, the median eGFR did not decline from baseline: only 1 patient experienced an ischemic event, but the eGFR remained unchanged. In patients treated with dasatinib, the mean eGFR did not change significantly: 3 patients experienced a cardiac ischemic event, but in all patients the eGFR remained unchanged over time, while advanced age and metabolic alterations contributed to the ischemic events. This long-term follow-up has documented that imatinib may induce changes in the eGFR, which may contribute to the onset of ischemic events. Further analyses on larger series of CML patients are required to conclusively define the potential renal toxicity of second generation TKIs and the consequent risk of developing ischemic events.

Keywords: Cardiovascular events; Chronic myeloid leukemia; Estimated glomerular filtration.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Biotransformation
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Creatinine / blood
  • Dasatinib / adverse effects
  • Dasatinib / pharmacokinetics
  • Dasatinib / therapeutic use
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / pharmacokinetics
  • Imatinib Mesylate / therapeutic use
  • Kidney Tubules / drug effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / etiology
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use
  • Renal Insufficiency, Chronic / chemically induced*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology
  • Retrospective Studies
  • Young Adult

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Creatinine
  • nilotinib
  • Dasatinib