J-SKI will be able to elucidate whether the renal function recover or not after discontinuation of tyrosine kinase inhib

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LETTER TO THE EDITOR

J‑SKI will be able to elucidate whether the renal function recover or not after discontinuation of tyrosine kinase inhibitors Sho Okamoto1 · Hiroshi Ureshino1,2   · Shinya Kimura1,2 Received: 16 June 2020 / Revised: 5 July 2020 / Accepted: 7 July 2020 © Japanese Society of Hematology 2020

Dear Editor, We would like to thank Dr. Lucijanic and Dr. Krecak for their useful comments on our recent study [1].They pointed out the reason why the decline in renal function did not recover after the discontinuation of tyrosine kinase inhibitors (TKIs) which might be due to older age and more comorbidities in the patients. In the context of the relation between age and estimated glomerular filtration rate (eGFR), we found a significant correlation between duration of TKI treatment and eGFR [1], and also between age and eGFR (r = – 0.645, p = 0.0000508). However, there was no significant correlation between duration of TKI treatment and age (r = 0.172, p = 0.338) (Fig. 1) in the cohort. The median age at TKI-discontinuation of the patients treated with imatinib was 61  years (range 53–87  years), whereas that of the patients treated with dasatinib or nilotinib was 77 years (38–85 years). Hence, we believe that the patients’ age was not unfavorably biased against the imatinib treatment group.

Our study cohort included six patients with hypertension and only one of those had diabetes mellitus concomitantly. The age-standardized prevalence of hypertension in Japanese in 2009 has been reported to be 31.8%, which is comparable to the prevalence in the British (31.2%) and American (34.5%) populations in the same period [2]. Therefore, hypertension and diabetes are not particularly frequent among patients in our study cohort. Although many confounders would exist in our study, the sample size was too small for using enough parameters in the multivariate analysis. We fully agree to Lucijanic and Krecak’s suggestion to compare with matched control group in patients’ clinical characteristics. That is our future issue and essential for clarifying the true eGFR changes without the effects of aging and/or comorbidities. Ongoing multicenter large scaled-observational study of the Japanese patients with CML after discontinuation of TKIs (JSH-J-SKI; UMIN000037535) will contribute to elucidate whether the renal function recovers or not after the achievement of TFR.

* Hiroshi Ureshino sr0795@cc‑saga‑u.ac.jp 1



Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, 5‑1‑1 Nabeshima, Saga 849‑8501, Japan



Department of Drug Discovery and Biomedical Sciences, Saga University, Saga, Japan

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S. Okamoto et al.

Fig. 1  Correlation between age at diagnosis and eGFR at TKI stop (left panel); age at diagnosis and TKI treatment time (right panel)

Compliance with ethical standards  Conflict of interest  The authors declare that they have no conflict of interest.

Reference 1. Okamoto S, Ureshino H, Kawaguchi A, Miyazono M, Ikeda Y, Kimura S. Asse