Tsuda Mariko, Hirata Akie, Tokunaga Shoji, Masuda Toru, Haji Shojiro, Kimura Daisaku, Nojiri Chinatsu, Nakashima Yasuhiro, Shiratsuchi Motoaki, Kato Koji, Miyamoto Toshihiro, Akashi Koichi, Nakashima Naoki, Ogawa Yoshihiro
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Medical Information Center, Kyushu University Hospital, Fukuoka, Japan.
Int J Hematol. 2022 Dec;116(6):863-870. doi: 10.1007/s12185-022-03433-6. Epub 2022 Aug 6.
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). However, TKI-related chronic renal toxicity has been reported, particularly in patients with hypertension. We assessed whether incidental use of specific types of antihypertensive drugs, including renin-aldosterone-angiotensin system inhibitors (RAASis), affects the change in estimated glomerular filtration rate (eGFR) during TKI treatment. We retrospectively analyzed all eGFR measurements during TKI treatment for 142 CML patients at Kyushu University Hospital, estimating the rate of eGFR change using a mixed-effects model. Overall, a significant interaction was found between the type of antihypertensive medication used and the yearly change in eGFR (P < 0.01), with RAASi users exhibiting the most rapid decrease in eGFR (- 5.5%/year). The analysis by TKI used showed that the interaction was significant only in imatinib and bosutinib users (P < 0.01 and P = 0.04, respectively). The yearly rate of eGFR decrease was the most notable in RAASi users, at - 5.7 (- 6.6, - 4.9) and - 10.1 (- 12.3, - 7.9) for imatinib and bosutinib users, respectively. Our findings indicate that eGFR should be carefully monitored in patients taking these TKIs.
酪氨酸激酶抑制剂(TKIs)彻底改变了慢性髓性白血病(CML)的治疗方式。然而,已有报道称TKIs会导致慢性肾毒性,尤其是在高血压患者中。我们评估了偶然使用特定类型的抗高血压药物,包括肾素 - 醛固酮 - 血管紧张素系统抑制剂(RAASis),是否会影响TKI治疗期间估计肾小球滤过率(eGFR)的变化。我们回顾性分析了九州大学医院142例CML患者在TKI治疗期间的所有eGFR测量值,使用混合效应模型估计eGFR变化率。总体而言,发现所用抗高血压药物类型与eGFR的年度变化之间存在显著交互作用(P < 0.01),使用RAASi的患者eGFR下降最快(-5.5%/年)。按使用的TKI进行分析表明,这种交互作用仅在伊马替尼和博舒替尼使用者中显著(分别为P < 0.01和P = 0.04)。对于伊马替尼和博舒替尼使用者,RAASi使用者的eGFR年度下降率最为显著,分别为-5.7(-6.6,-4.9)和-10.1(-12.3,-7.9)。我们的研究结果表明,服用这些TKIs的患者应密切监测eGFR。