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Relationship between anti-erythropoietin receptor autoantibodies and responsiveness to erythropoiesis-stimulating agents in patients on hemodialysis: a multi-center cross-sectional study

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Abstract

Background

A decreased response to erythropoiesis-stimulating agents (ESAs) leads to refractory anemia and worse prognosis in patients with chronic kidney disease. We examined the association between autoantibodies to the erythropoietin receptor (EPOR) and responsiveness to ESAs in patients on maintenance hemodialysis.

Methods

A total of 108 Japanese patients on maintenance hemodialysis at three institutions were enrolled. Sera from these patients were screened for anti-EPOR antibodies using an enzyme-linked immunosorbent assay. An ESA resistance index (ERI) was calculated, and patients in the highest ERI quartile were defined as ESA hyporesponsive.

Results

Anti-EPOR antibodies were detected in 11 patients (10%). Body mass index and hemoglobin, platelet, magnesium, and ferritin levels decreased with higher ERI levels. On the other hand, C-reactive protein (CRP) levels and the prevalence of anti-EPOR antibodies increased with higher ERI levels. In multivariate analysis, the presence of anti-EPOR antibodies together with CRP was a significant risk factor for ESA hyporesponsiveness.

Conclusions

Anti-EPOR antibodies were detected in patients on maintenance hemodialysis, and these autoantibodies were independent factors for hyporesponsiveness to ESAs in these patients.

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Acknowledgements

We thank Hiroka Yamazaki, Yoshiko Isaki, and Mayumi Fukuta for their assistance with data collection.

Funding

This work was supported by a grant from The Kidney Foundation, Japan (number JKFB17-3) and the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI) Grant number JP16K09608.

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Authors and Affiliations

  1. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan

    Akinori Hara, Taito Miyake, Shinji Kitajima, Tadashi Toyama, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Kengo Furuichi & Takashi Wada

  2. Department of Environmental and Preventive Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Akinori Hara & Hiroyuki Nakamura

  3. Department of Internal Medicine, Mizuho Hospital, Kahoku, Japan

    Yoshitaka Koshino & Yukie Kurokawa

  4. Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Yasuyuki Shinozaki, Taito Miyake, Shinji Kitajima, Tadashi Toyama, Yasunori Iwata, Norihiko Sakai, Miho Shimizu & Takashi Wada

  5. Department of Nephrology, Kanazawa Medical Center, Kanazawa, Japan

    Yasuyuki Shinozaki

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  1. Akinori Hara
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  2. Yoshitaka Koshino
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  11. Kengo Furuichi
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  12. Hiroyuki Nakamura
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Corresponding author

Correspondence to Akinori Hara.

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Conflict of interest

All the authors have declared no competing interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the medical ethics committee of Kanazawa University at which the studies were conducted (approval number 1590) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Hara, A., Koshino, Y., Kurokawa, Y. et al. Relationship between anti-erythropoietin receptor autoantibodies and responsiveness to erythropoiesis-stimulating agents in patients on hemodialysis: a multi-center cross-sectional study. Clin Exp Nephrol 24, 88–95 (2020). https://doi.org/10.1007/s10157-019-01787-6

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  • DOI: https://doi.org/10.1007/s10157-019-01787-6

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