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Long-acting erythropoiesis-stimulating agent (ESA) induces physiological erythropoiesis via improvement of iron availability

  • Nephrology - Original Paper
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Abstract

Purpose

Previous studies reported that the long-acting erythropoiesis-stimulating agent (ESA) significantly suppresses the expression of hepcidin, which regulates iron availability. In this study, we compared the iron availability for erythropoiesis between short and long-acting ESA over a long period.

Methods

We enrolled 69 hemodialysis patients in this study. All patients were treated with short-acting ESA (epoetin-α or epoetin-β) for the first 30 months. Then, all patients switched to long-acting ESA (continuous erythropoietin receptor activator-methoxy polyethylene glycol-epoetin beta) for the next 30 months. We measured their blood levels of Hb, ferritin, iron, total iron-binding capacity, intact-parathyroid hormone, calcium, phosphate, albumin, and highly sensitive CRP level.

Results

There was no significant change in the dose of short or long-acting ESA during the study period. Compared with the short-acting ESA period, the mean hemoglobin (Hb) and transferrin saturation levels were significantly increased in the long-acting ESA period (from 10.3 ± 0.2 to 10.6 ± 0.3 g/dL). On the other hand, the mean serum ferritin level (from 72 ± 22.2 to 56.3 ± 14 ng/mL) and the dose of IV iron (from 108 ± 63 to 53 ± 27 mg/month) were significantly decreased in the long-acting ESA period.

Conclusion

In this study, we found that anemia treatment with long-acting ESA attenuated the iron utilization for erythropoiesis and maintained target Hb levels without requiring a higher dose of IV iron or ESA.

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Acknowledgements

We gratefully acknowledge the efforts and contributions of the nephrologists who participated in this study. We thank Dr. Kouji Shibuya (Department of Internal Medicine, Sumiyoshigawa Hospital, Hyogo), Dr. Takashi Miyamoto (Miyamoto Clinic, Hyogo), Dr. Haruki Ohue (Ohue Clinic, Hyogo), Dr. Mana Hiwasa (Hiwasa Clinic, Hyogo), Dr. Takuo Iwasaki (Iwasaki Clinic, Hyogo), Dr. Touru Iwasaki (Iwasaki Internal Clinic, Hyogo), Dr. Teturo Nagai (Nagai Clinic, Hyogo), Dr. Noriko Tanka (Department of Internal Medicine, Tanaka Kitanoda Hospital, Osaka and Houjyou Tanaka Hospital, Hyogo), Dr. Ryouichi Yorifuji (Jinsei Clinic, Hyogo), Dr. Toshiaki Hirabayashi (Heimeikai Clinic, Hyogo), who conducted clinical research in our study.

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Authors and Affiliations

  1. Division of Kidney and Dialysis, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Japan

    Miwa Masumoto, Takahiro Kuragano, Chisa Takata, Risako Fukui, Yuki Mihara, Rina Okamoto, Takahide Iwasaki, Satoshi Ookawa, Makoto Aichi, Mana Yahiro, Arithoshi Kida & Masayshi Nanami

Authors
  1. Miwa Masumoto
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  2. Takahiro Kuragano
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  3. Chisa Takata
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  4. Risako Fukui
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  6. Rina Okamoto
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  12. Masayshi Nanami
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Contributions

MM and TK designed the study, analyzed the data and wrote the manuscript. TK, CT, TI, TO, KM, MY, AK and MN analyzed the data, contributed to the discussion and reviewed the manuscript.

Corresponding author

Correspondence to Takahiro Kuragano.

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Conflict of interest

Takahiro Kuragano declares having grants from Chugai Pharmaceutical, Pharmaceutical Company, Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., and Kyowa Kirin and received a speaker fee from Kyowa Kirin, Fuso Pharmaceutical Industries, Ltd., and Bayer Yakuhin, Ltd. Takahiro Kuragano received an advisory board fee from Astellas Pharma Inc. and Chugai Pharmaceutical.

Ethics approval

The protocol was approved by the Ethics Review Board of the Hyogo College of Medicine (approval number 419) in accordance with the ethical principles outlined in the 1975 Declaration of Helsinki as revised in 2013.

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Written informed consent was obtained from all patients.

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Written informed consent was obtained from all patients.

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Masumoto, M., Kuragano, T., Takata, C. et al. Long-acting erythropoiesis-stimulating agent (ESA) induces physiological erythropoiesis via improvement of iron availability. Int Urol Nephrol 54, 1079–1084 (2022). https://doi.org/10.1007/s11255-021-02965-w

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