International Journal of Hematology

, Volume 109, Issue 1, pp 59–69 | Cite as

Deregulated iron metabolism in bone marrow from adenine-induced mouse model of chronic kidney disease

  • Tomoko Kimura
  • Takahiro KuraganoEmail author
  • Kiyoko Yamamoto
  • Masayoshi Nanami
  • Yukiko Hasuike
  • Takeshi Nakanishi
Original Article


Although the primary cause of anemia in chronic kidney disease (CKD) is lack of sufficient erythropoietin (EPO), other factors may be involved, including the deregulation of iron metabolism. To clarify the mechanism of deranged erythropoiesis in CKD, we evaluated bone marrow (BM) cells in adenine-induced CKD mice. They showed even higher EPO expression in the kidney. Hepatic hepcidin mRNA and plasma hepcidin and ferritin levels were increased. Flow cytometry revealed a decrease in the number of cells expressing transferrin receptor (TfR), or late erythroid progenitors in BM; these cells correspond to proerythroblasts, and basophilic and polychromatic erythroblasts. In CKD mice, levels of erythroferrone mRNA in BM and splenic cells were significantly decreased, and MafB protein levels in BM cells were significantly increased. These results suggest that, in BM, the decrease in TfR, which may be associated with increased MafB levels, and the decrease in erythroferrone increase hepatic hepcidin expression, which may perturb iron recycling and erythropoiesis.


TfR Hepcidin MafB Renal anemia CKD 



We gratefully acknowledge the efforts and contributions of this study. We thank Dr. Takanori Nagai, Miss. Ayako Goto, and Mrs. Eiko Akabane.

Authors’ contributions

TK, TK, RL and TN designed the trial. TK and KY performed the animal study. TK and TH measured the parameters. MN and YH performed the statistical analyses. All authors contributed to the data analysis and wrote the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

None declared.


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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Tomoko Kimura
    • 1
  • Takahiro Kuragano
    • 1
    Email author
  • Kiyoko Yamamoto
    • 1
  • Masayoshi Nanami
    • 1
  • Yukiko Hasuike
    • 1
  • Takeshi Nakanishi
    • 1
  1. 1.Division of Kidney and Dialysis, Department of Internal MedicineHyogo College of MedicineNishinomiyaJapan

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