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接受酪氨酸激酶抑制剂治疗的慢性髓性白血病患者的估计肾小球滤过率变化

Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

作者信息

Yilmaz Musa, Lahoti Amit, O'Brien Susan, Nogueras-González Graciela M, Burger Jan, Ferrajoli Alessandra, Borthakur Gautam, Ravandi Farhad, Pierce Sherry, Jabbour Elias, Kantarjian Hagop, Cortes Jorge E

机构信息

Department of Hematology and Oncology, Baylor College of Medicine, Houston, Texas.

Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Cancer. 2015 Nov 1;121(21):3894-904. doi: 10.1002/cncr.29587. Epub 2015 Jul 28.

Abstract

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.

摘要

背景

长期使用酪氨酸激酶抑制剂(TKIs)可能导致先前未被认识到的不良事件。本研究评估了接受伊马替尼、达沙替尼和尼洛替尼治疗的慢性期(CP)慢性髓性白血病(CML)患者急性肾损伤(AKI)和慢性肾脏病(CKD)的发生率。

方法

分析了468例接受TKIs治疗的新诊断CP CML患者。从治疗开始至最后一次随访(中位时间为52个月),跟踪分子和细胞遗传学反应数据、肌酐和肾小球滤过率(GFR)。采用肾脏病饮食改良方程估算GFR。

结果

19例患者(4%)发生了TKI相关的AKI。与达沙替尼和尼洛替尼相比,伊马替尼与AKI的发生率较高相关(P = 0.014)。58例患者(14%)在接受TKI治疗时发生了CKD;其中49例患者(84%)在接受伊马替尼治疗时发生了CKD(P < 0.001)。除伊马替尼外,年龄、高血压病史和糖尿病也与CKD的发生相关。在基线时无CKD的患者中,伊马替尼随时间推移会降低GFR。有趣的是,伊马替尼并未导致有CKD病史患者的GFR显著下降。伊马替尼、达沙替尼和尼洛替尼在治疗3个月后可提高平均GFR,其中尼洛替尼导致的升高最为显著(P < 0.001)。AKI或CKD对总体细胞遗传学和分子反应率或生存率无显著影响。

结论

在CP CML患者的CKD情况下,TKIs的使用可能是安全的,但仍需密切监测。

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