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Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials

  • Nephrology - Original Paper
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Abstract

Purpose

Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies.

Methods

We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software.

Results

We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea.

Conclusion

HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

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Authors and Affiliations

  1. Department of Internal Medicine, SSM Health St. Mary’s Hospital-St.Louis, 6420 Clayton Rd, Suite 2218, St. Louis, MO, 63117, USA

    Mohamed M. G. Mohamed, Mosunmoluwa Oyenuga & Safia Shaikh

  2. Department of Internal Medicine, University of Minnesota Medical School, Minneapolis, MN, USA

    Abayomi Oyenuga

  3. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA

    Babikir Kheiri

  4. Department of Nephrology, SSM Health St. Mary’s Hospital-St. Louis, St. Louis, MO, USA

    Christian Nwankwo

Authors
  1. Mohamed M. G. Mohamed
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  2. Mosunmoluwa Oyenuga
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  3. Safia Shaikh
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  4. Abayomi Oyenuga
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  5. Babikir Kheiri
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  6. Christian Nwankwo
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Contributions

Research idea and study design: SS; MM: data acquisition; MO, MM, SS: data analysis/interpretation; MM, AO, MO: editing and review; AO, BK, CN: supervision or mentorship; BK, CN. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated, and resolved, including with documentation in the literature if appropriate.

Corresponding author

Correspondence to Mohamed M. G. Mohamed.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

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Mohamed, M.M.G., Oyenuga, M., Shaikh, S. et al. Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials. Int Urol Nephrol 55, 167–171 (2023). https://doi.org/10.1007/s11255-022-03300-7

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  • DOI: https://doi.org/10.1007/s11255-022-03300-7

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