Division of Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto I, Sapienza University, Via Benevento 6, 00161, Rome, Italy.
Department of Statistical Sciences, Policlinico Umberto I, Sapienza University, Rome, Italy.
Ann Hematol. 2018 Oct;97(10):1803-1808. doi: 10.1007/s00277-018-3375-9. Epub 2018 May 27.
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.
我们研究了一线接受酪氨酸激酶抑制剂（TKI）治疗的慢性髓性白血病（CML）患者的中位估算肾小球滤过率（eGFR）变化。在一家单中心回顾性分析了 397 例患者-320 例一线接受伊马替尼治疗，25 例接受达沙替尼治疗，53 例接受尼洛替尼治疗。所有患者在基线时、治疗后 6 个月和 12 个月以及最后一次随访时根据慢性肾脏病流行病学合作方程计算 eGFR。考虑到治疗第一年期间 eGFR 的变化，并排除其他可能的心血管危险因素，我们还考虑了在该单一参数改变的患者中心血管事件的百分比。伊马替尼诱导 eGFR 中位数降低（p=0.01）：42 例接受伊马替尼治疗的患者发生了心血管事件，与 eGFR 改变有关，而无其他心血管危险因素。接受尼洛替尼治疗的患者 eGFR 从基线没有下降：只有 1 例发生缺血性事件，但 eGFR 保持不变。接受达沙替尼治疗的患者 eGFR 没有显著变化：3 例发生心脏缺血性事件，但在所有患者中，eGFR 随时间保持不变，而高龄和代谢改变导致缺血性事件发生。这项长期随访记录表明，伊马替尼可能会引起 eGFR 的变化，这可能会导致缺血性事件的发生。需要对更大系列的 CML 患者进行进一步分析，以明确第二代 TKI 的潜在肾毒性以及发生缺血性事件的风险。
