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Long-term treatment of chronic kidney disease patients with anemia using hypoxia-inducible factor prolyl hydroxylase inhibitors: potential concerns

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Abstract

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved in several countries as a supplement or even an alternative to the clinical treatment of anemia in patients with chronic kidney disease (CKD). Activation of HIF by HIF-PHIs effectively increases hemoglobin (Hb) level in CKD patients by inducing multiple HIF downstream signaling pathways. This indicates that HIF-PHIs have effects beyond erythropoietin, while their potential benefits and risks should be necessarily assessed. Multiple clinical trials have largely demonstrated the efficacy and safety of HIF-PHIs in the short-term treatment of anemia. However, in terms of long-term administration, especially over 1 year, the benefits and risks of HIF-PHIs still need to be assessed. Particular attention should be paid to the risk of kidney disease progression, cardiovascular events, retinal diseases, and tumor risk. This review aims to summarize the current potential risks and benefits of HIF-PHIs in CKD patients with anemia and further discuss the mechanism of action and pharmacological properties of HIF-PHIs, in order to provide direction and theoretical support for future studies.

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Funding

This study was supported by the National Key Research and Development Program (2022YFC2705100, 2019YFA0802700, and 2019YFA0802702) and the National Natural Science Foundation of China (82090020, 82090022, 81830020, 82070701, and 82170689).

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Authors and Affiliations

  1. Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, 211166, China

    Jia He, Zhanjun Jia, Aihua Zhang & Mi Bai

  2. Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, 210029, China

    Jia He, Zhanjun Jia, Aihua Zhang & Mi Bai

  3. Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, China

    Zhanjun Jia, Aihua Zhang & Mi Bai

  4. Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, China

    Mi Bai

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Writing—original draft preparation: J.H. and M.B. Writing—review and editing: M.B., Z.J.J., and A.H.Z. Supervision: Z.J.J. and A.H.Z. All authors have read and agreed to the published version of the manuscript.

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He, J., Jia, Z., Zhang, A. et al. Long-term treatment of chronic kidney disease patients with anemia using hypoxia-inducible factor prolyl hydroxylase inhibitors: potential concerns. Pediatr Nephrol 39, 37–48 (2024). https://doi.org/10.1007/s00467-023-06031-8

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