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Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) on anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD): a systematic review and meta-analysis

  • Nephrology - Review
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Abstract

Purpose

HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitor) was developed to improve renal anemia. This study was to evaluate the efficiency and safety of HIF-PHI in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).

Methods

The literature was extracted from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Wanfang database. Statistical tests and forest plots were depicted by Review Manager Version 5.3. The primary outcome was a change in hemoglobin level from baseline (ΔHb). Secondary outcomes were changes in ferritin (ΔFerritin), hepcidin (ΔHepcidin), and transferrin saturation from baseline (ΔTSAT), and adverse events (AEs). This study is registered with PROSPERO (registration number CRD42020199656).

Results

Ten trials were included. The results showed that HIF-PHI improved the ΔHb [SMD 3.03 (95% CI 2.10, 3.96), P < 0.00001] in NDD patients. HIF-PHI reduced hepcidin levels in the NDD patients [SMD − 1.44 (95% CI − 2.19–0.70), P = 0.0002]. ΔFerritin values were reduced significantly in the HIF-PHI group [SMD − 1.08 (95% CI − 1.63–0.53), P = 0.0001]. However, ΔTSAT values showed no significant difference in the HIF-PHI group compared to the placebo group [SMD − 0.23 (95% CI − 0.66–0.21), P = 0.31]. In the safety assessment, HIF-PHI did not increase adverse events significantly [RR 0.98 (95% CI 0.88–1.10), P = 0.74].

Conclusion

HIF-PHI improves renal anemia and iron utilization disorder in NDD-CKD patients, without significantly more adverse events.

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Acknowledgements

This work was supported by the Natural Science Foundation of Yongchuan District (No. Ycstc, 2019nb0215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Lingjiang Road, Yuzhong District, Chongqing, 400010, China

    Siliang Zhang, Shuqin Xie, Jianwei Chen & Yuan Yu

  2. Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, 400030, China

    Jing Guo

  3. Center of Urology and Nephrology, Yongchuan People’s Hospital of Chongqing, Chongqing, 402160, China

    Shenrun Yu

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  1. Siliang Zhang
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Correspondence to Yuan Yu.

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Zhang, S., Guo, J., Xie, S. et al. Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) on anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD): a systematic review and meta-analysis. Int Urol Nephrol 53, 1139–1147 (2021). https://doi.org/10.1007/s11255-020-02671-z

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