Effects of SLC22A2 808G>T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy

• Abumiya, Maiko

• TAKAHASHI, Naoto

• Takahashi, Saori

• Yoshioka, Tomoko

• Kameoka, Yoshihiro

• Miura, Masatomo

Abstract

The purpose of this study was to investigate the effects of SLC22A2 808G>T polymorphism and trough concentrations (C 0 ) of bosutinib on serum creatinine in 28 patients taking bosutinib. At 1, 3, 6, 12, 24, and 36 months after administration, analysis of bosutinib C 0 and creatinine was performed at the same time of day. Significant correlations were observed between bosutinib C 0 and the change rate of serum creatinine or the estimated glomerular filtration rate (eGFR; r  = 0.328, P  < 0.001 and r  = − 0.315, P  < 0.001, respectively). These correlations were particularly high in patients having the SLC22A2 808G/G genotype ( r  = 0.345 and r  = − 0.329, respectively); however, in patients having the 808T allele, there were no significant differences. In multivariate analyses, the SLC22A2 808G/G genotype, patient age, bosutinib C 0 and second-line or later bosutinib were independent factors influencing the change rate of creatinine. Bosutinib elevated serum creatinine through organic cation transporter 2 (OCT2). We observed a 20% increase in serum creatinine with a median bosutinib C 0 of 63.4–73.2 ng/mL. Periodic measurement of serum creatinine after bosutinib therapy is necessary to avoid progression to severe renal dysfunction from simple elevation of creatinine mediated by OCT2 following bosutinib treatment.

Journal

• Scientific Reports

  Scientific Reports 11 (6362), 2021

  Springer nature

Keywords

• Multidisciplinary

Details

• CRID: 1050853179581182976
• NII Article ID: 120007172092
• ISSN: 20452322
• DOI: 10.1038/s41598-021-85757-7
• HANDLE: 10295/00005840
• Web Site: https://air.repo.nii.ac.jp/records/5523
• Web Site: https://www.nature.com/articles/s41598-021-85757-7.pdf
• Web Site: https://www.nature.com/articles/s41598-021-85757-7
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN