Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 6, 2021; 9(34): 10616-10625
Published online Dec 6, 2021. doi: 10.12998/wjcc.v9.i34.10616
Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease
Chao Kan, Xu Lu, Rui Zhang
Chao Kan, Xu Lu, Department of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
Rui Zhang, Department of Nephrology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519070, Guangdong Province, China
Author contributions: Zhang R initiated the project and gave constructive comments and suggestions for the manuscript; Kan C drafted the manuscript; Lu X provided assistance with the figures and tables; and all authors have read and approved the manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rui Zhang, PhD, Chief Physician, Department of Nephrology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), No. 79 Kangning Road, Xiangzhou District, Zhuhai 519070, Guangdong Province, China. zhangruidoctor@163.com
Received: May 7, 2021
Peer-review started: May 7, 2021
First decision: July 26, 2021
Revised: August 12, 2021
Accepted: October 25, 2021
Article in press: October 25, 2021
Published online: December 6, 2021
Processing time: 207 Days and 0.4 Hours
Abstract
BACKGROUND

Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease (CKD). Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD, but few have evaluated their mutual connection. Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches; however, with the availability of hypoxia-inducible factor (HIF) stabilizers such as roxadustat, more therapeutic choices for renal anemia are expected in the future. However, the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.

AIM

To summarize the relationship between renal anemia and abnormal bone metabolism, and to discuss the influence of hypoxia on bone metabolism.

METHODS

CNKI and PubMed searches were performed using the key words “chronic kidney disease,” “abnormal bone metabolism,” “anemia,” “hypoxia,” and “HIF” to identify relevant articles published in multiple languages and fields. Reference lists from identified articles were reviewed to extract additional pertinent articles. Then we retrieved the Abstract and Introduction and searched the results from the literature, classified the extracted information, and summarized important information. Finally, we made our own conclusions.

RESULTS

There is a bidirectional relationship between renal anemia and abnormal bone metabolism. Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism, blood cell production, and survival rates through multiple pathways. Anemia will further attenuate the normal bone growth. The hypoxic environment regulates bone morphogenetic protein, vascular endothelial growth factor, and neuropilin-1, and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes. Hypoxia preconditioning of mesenchymal stem cells (MSCs) can enhance their paracrine effects and promote fracture healing. Concurrently, hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23. Hypoxia potentially improves bone metabolism, but it still carries potential risks. The optimal concentration and duration of hypoxia remain unclear.

CONCLUSION

There is a bidirectional relationship between renal anemia and abnormal bone metabolism. Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Keywords: Chronic kidney disease; Abnormal bone metabolism; Anemia; Hypoxia; Hypoxia-inducible factor

Core Tip: Anemia and abnormal bone metabolism are complications in patients with chronic kidney disease (CKD), which seriously affect the prognosis of patients. This review summarizes the findings from recent studies on renal anemia and abnormal bone metabolism in patients with CKD. The bidirectional relationship between anemia and abnormal bone metabolism in patients with CKD is discussed. While studying the treatment of anemia with hypoxia-inducible factor (HIF), it was found that hypoxia can affect bone metabolism, but there is no consensus on the efficacy of HIF stabilizers in renal bone disease.