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Rapid decrease in eGFR with concomitant use of tyrosine kinase inhibitors and renin–aldosterone–angiotensin system inhibitors in patients with chronic myelogenous leukemia

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Abstract

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.

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Author notes

  1. Mariko Tsuda and Akie Hirata contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Mariko Tsuda, Toru Masuda, Shojiro Haji, Daisaku Kimura, Yasuhiro Nakashima, Motoaki Shiratsuchi & Yoshihiro Ogawa

  2. Medical Information Center, Kyushu University Hospital, Fukuoka, Japan

    Akie Hirata, Shoji Tokunaga, Chinatsu Nojiri & Naoki Nakashima

  3. Department of Hematology, Iizuka Hospital, Iizuka, Japan

    Motoaki Shiratsuchi

  4. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Koji Kato, Toshihiro Miyamoto & Koichi Akashi

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  1. Mariko Tsuda
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Correspondence to Yasuhiro Nakashima.

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Conflict of interest

Mariko Tsuda received honoraria/lecture fees from Otsuka related to this study. Sojiro Haji received honoraria/lecture fees from Kyowa Kirin unrelated to this study. Yasuhiro Nakashima received research grants from the Japanese Society of Hematology, and research grant supports from Chugai, Kyowa Kirin, Daiichi Sankyo and SRL, honoraria/lecture fees from Otsuka related to this study, and Chugai, Kyowa Kirin, Ono and Sanofi, unrelated to this study. Motoaki Shiratsuchi received research grant supports from Chugai, Kyowa Kirin, Daiichi Sankyo, MSD and SRL, honoraria/lecture fees from Otsuka related to this study, and Chugai, Kyowa Kirin, Ono and Sanofi, unrelated to this study. Koji Kato received research grant supports from Chugai, Takeda, Kyowa Kirin, AbbVie, Novartis, Eisai, Janssen, Celgene, Ono and Daiichi Sankyo, honoraria/lecture fees from Kyowa Kirin, Novartis, Takeda and Chugai, unrelated to this study. Toshihiro Miyamoto received honoraria/lecture fees from Takeda, Otsuka, MSD, Kyowa Kirin, Janssen, Astellas and AbbVie. Koichi Akashi received research grant supports from Otsuka, Nippon Shinyaku, Taiho, Asahi Kasei, Chugai, Takeda, Kyowa Kirin, AbbVie, Sumitomo Dainippon, Astellas, Bristol Myers Squibb and Eisai, honoraria/lecture fees from AbbVie, Eisai, Ono, Kyowa Kirin, Chugai, Pfizer, Bristol Myers Squibb and Janssen, unrelated to this study. Naoki Nakashima received research grant supports from Pfizer unrelated to this study. Yoshihiro Ogawa received research grant supports from Kyowa Kirin, Taisho, Mochida, Cosmic Corporation, Fujifilm, Mitsubishi Tanabe, AstraZeneca, Nippon Boehringer lngelheim, Eisai, Abbott, Chugai, Pfizer, Tsumura, Otsuka, Taiho, Zeria and Fujiyakuhin, honoraria/lecture fees from Novo Nordisk Pharma and Taisho, unrelated to this study. The other authors have no conflicts of interest to declare.

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Tsuda, M., Hirata, A., Tokunaga, S. et al. Rapid decrease in eGFR with concomitant use of tyrosine kinase inhibitors and renin–aldosterone–angiotensin system inhibitors in patients with chronic myelogenous leukemia. Int J Hematol 116, 863–870 (2022). https://doi.org/10.1007/s12185-022-03433-6

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  • DOI: https://doi.org/10.1007/s12185-022-03433-6

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