Ayalew Zekarias Seifu, Azibte Gebeyehu Tessema, Tadesse Fisihatsion, Legesse Biruk Abate, Kiflu Zerubabel Getahun, Weldeamanuel Mahlet Tsige, Tsige Kibrekidusan Aynekulu, Molla Bereket Abraha, Ejigu Addisu Melkie
Department of Internal Medicine Addis Ababa University Addis Ababa Ethiopia.
Department of Internal Medicine, Division of Hematology Addis Ababa University Addis Ababa Ethiopia.
EJHaem. 2024 Jul 31;5(4):749-756. doi: 10.1002/jha2.988. eCollection 2024 Aug.
The efficacy of BCR-ABL tyrosine kinase inhibitors (TKIs) in treating chronic myelogenous leukemia and other malignancies is well-documented. However, concerns about potential nephrotoxicity have raised questions. This study, conducted at Tikur Anbesa Specialized Hospital (TASH) in Addis Ababa, Ethiopia, aimed to investigate the association between TKIs and renal toxicities.
A hospital-based cross-sectional design was used to enroll 260 TASH patients actively receiving BCR-ABL TKIs. Demographic information, diagnoses, treatment details, and laboratory test results were collected for each participant's Electronic Medical Record. The primary goal was to assess adverse renal events, a combination of events of a decrease in estimated glomerular filtration rate (eGFR) exceeding 30% from baseline, significant proteinuria, and a diagnosis of acute kidney injury (AKI) or chronic kidney disease (CKD). A logistic regression model was used to analyze the data and identify factors associated with developing adverse renal events.
Our analysis revealed a statistically significant decrease in eGFR following treatment with TKIs. However, the observed rate of adverse renal events (13.1%) was lower than reported in some previous studies. Factors significantly associated with adverse renal events included longer TKI duration, male sex (protective), hypertension, HIV infection, and achieving complete molecular remission and/or a complete hematologic response. No significant associations were found with diabetes mellitus, age, angiotensin-converting enzyme inhibitors use, or baseline creatinine level.
While this study found that BCR-ABL TKIs can lead to a decline in eGFR, AKI, and CKD, it also demonstrated that they were relatively safer in our study population.
BCR-ABL酪氨酸激酶抑制剂（TKIs）在治疗慢性粒细胞白血病和其他恶性肿瘤方面的疗效已有充分记录。然而，对潜在肾毒性的担忧引发了一些问题。这项在埃塞俄比亚亚的斯亚贝巴的提库尔·安贝萨专科医院（TASH）进行的研究，旨在调查TKIs与肾毒性之间的关联。
采用基于医院的横断面设计，纳入260名正在积极接受BCR-ABL TKIs治疗的TASH患者。从每位参与者的电子病历中收集人口统计学信息、诊断结果、治疗细节和实验室检查结果。主要目标是评估不良肾脏事件，即估计肾小球滤过率（eGFR）较基线下降超过30%、大量蛋白尿以及急性肾损伤（AKI）或慢性肾脏病（CKD）诊断等事件的综合情况。使用逻辑回归模型分析数据，确定与发生不良肾脏事件相关的因素。
我们的分析显示，TKIs治疗后eGFR有统计学意义的下降。然而，观察到的不良肾脏事件发生率（13.1%）低于一些先前研究报告的发生率。与不良肾脏事件显著相关的因素包括TKIs治疗时间较长、男性（有保护作用）、高血压、HIV感染以及实现完全分子缓解和/或完全血液学缓解。未发现与糖尿病、年龄、使用血管紧张素转换酶抑制剂或基线肌酐水平有显著关联。
虽然本研究发现BCR-ABL TKIs可导致eGFR下降、AKI和CKD，但也表明在我们的研究人群中它们相对更安全。
