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.
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.
Authors: Moshe Talpaz; Neil P Shah; Hagop Kantarjian; Nicholas Donato; John Nicoll; Ron Paquette; Jorge Cortes; Susan O'Brien; Claude Nicaise; Eric Bleickardt; M Anne Blackwood-Chirchir; Vishwanath Iyer; Tai-Tsang Chen; Fei Huang; Arthur P Decillis; Charles L Sawyers Journal: N Engl J Med Date: 2006-06-15 Impact factor: 91.245
Authors: Paul W Manley; Nikolaus Stiefl; Sandra W Cowan-Jacob; Susan Kaufman; Jürgen Mestan; Markus Wartmann; Marion Wiesmann; Richard Woodman; Neil Gallagher Journal: Bioorg Med Chem Date: 2010-08-14 Impact factor: 3.641
Authors: Ravindra L Mehta; John A Kellum; Sudhir V Shah; Bruce A Molitoris; Claudio Ronco; David G Warnock; Adeera Levin Journal: Crit Care Date: 2007 Impact factor: 9.097
Authors: Elizabeth M Pinder; Gurprit S S Atwal; Abraham A Ayantunde; Sarah Khan; Mike Sokal; Tom McCulloch; Simon L Parsons Journal: Sarcoma Date: 2007
Authors: Vladimir Tesar; Kazimierz Ciechanowski; York Pei; Irina Barash; Megan Shannon; Ray Li; Jason H Williams; Matteo Levisetti; Steven Arkin; Andreas Serra Journal: J Am Soc Nephrol Date: 2017-08-24 Impact factor: 10.121
Authors: Jorge E Cortes; Giuseppe Saglio; Hagop M Kantarjian; Michele Baccarani; Jiří Mayer; Concepción Boqué; Neil P Shah; Charles Chuah; Luis Casanova; Brigid Bradley-Garelik; George Manos; Andreas Hochhaus Journal: J Clin Oncol Date: 2016-05-23 Impact factor: 44.544