Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.
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.
['Yilmaz|Musa|M|', 'Lahoti|Amit|A|', "O'Brien|Susan|S|", 'Nogueras-González|Graciela M|GM|', 'Burger|Jan|J|', 'Ferrajoli|Alessandra|A|', 'Borthakur|Gautam|G|', 'Ravandi|Farhad|F|', 'Pierce|Sherry|S|', 'Jabbour|Elias|E|', 'Kantarjian|Hagop|H|', 'Cortes|Jorge E|JE|']
D058186:Acute Kidney Injury D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D003404:Creatinine D000069439:Dasatinib D004305:Dose-Response Relationship, Drug D005260:Female D005500:Follow-Up Studies D005919:Glomerular Filtration Rate D006801:Humans D000068877:Imatinib Mesylate D015994:Incidence D007668:Kidney D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive D008297:Male D008875:Middle Aged D047428:Protein Kinase Inhibitors D011505:Protein-Tyrosine Kinases D011743:Pyrimidines D051436:Renal Insufficiency, Chronic D012189:Retrospective Studies D016896:Treatment Outcome D055815:Young Adult
glomerular filtration rate changes tyrosine kinase inhibitor kidney injury chronic myeloid leukemia (CML) imatinib dasatinib nilotinib outcome