UC Irvine

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.