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Review
. 2023 Aug 7;45(8):6550-6563.
doi: 10.3390/cimb45080413.

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease

Nava Yugavathy  1 , Bashar Mudhaffar Abdullah  2 , Soo Kun Lim  3 , Abdul Halim Bin Abdul Gafor  4 , Muh Geot Wong  5   6 , Sunita Bavanandan  7 , Hin Seng Wong  8 , Hasniza Zaman Huri  1
Affiliations
Review

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease

Nava Yugavathy et al. Curr Issues Mol Biol. .

Abstract

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.

Keywords: HIF-PHI; erythropoietin deficiency anaemia; inflammation; pharmacogenetics; precision medicine.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 2
Figure 2
Pleiotropic effects of prolyl hydroxylase (PH) inhibition. HIF, hypoxia-inducible factor. Improved iron [67,68]; improved lipid profile [69]; glucose profile [52]; protective against kidney injury [70]; development of cancer [71], cardiovascular risk [72]; inflammation [73,74].
Figure 1
Figure 1
Inflammatory cytokines leading to anaemia. IL-6, interleukin-6; IL-1, interleukin-1; IFN-α, -β, -γ, interferon-α, -β, -γ; TNF-α, tumour necrosis factor-α; EBFU, erythroid burst-forming units; ECFO, erythroid colony-forming units; ↑, increase; ↓, decrease; FNP, ferroportin; DMT1, divalent metal transporter 1 ([12] (permission obtained)).
See this image and copyright information in PMC

References

    1. Bonomini M., Del Vecchio L., Sirolli V., Locatelli F. New Treatment Approaches for the Anemia of CKD. Am. J. Kidney Dis. 2016;67:133–142. doi: 10.1053/j.ajkd.2015.06.030. - DOI - PubMed
    1. Drüeke T.B., Massy Z.A. Erythropoiesis-Stimulating Agents and Mortality. J. Am. Soc. Nephrol. 2019;30:907–908. doi: 10.1681/ASN.2019030266. - DOI - PMC - PubMed
    1. Lee K.-H., Ho Y., Tarng D.-C. Iron Therapy in Chronic Kidney Disease: Days of Future Past. Int. J. Mol. Sci. 2021;22:1008. doi: 10.3390/ijms22031008. - DOI - PMC - PubMed
    1. Batchelor E.K., Kapitsinou P., Pergola P.E., Kovesdy C.P., Jalal D.I. Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment. J. Am. Soc. Nephrol. 2020;31:456–468. doi: 10.1681/ASN.2019020213. - DOI - PMC - PubMed
    1. Fishbane S., El-Shahawy M.A., Pecoits-Filho R., Pham Van B., Houser M.T., Frison L., Little D.J., Guzman N.J., Pergola P.E. OLYMPUS: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, International Study of Roxadustat Efficacy in Patients with Non-Dialysis-Dependent (NDD) CKD and Anemia [Abstract TH-OR023] J. Am. Soc. Nephrol. 2019;30:6.