Iron metabolism and management: focus on chronic kidney disease

  • Anil K. Agarwal
    Correspondence: Anil K. Agarwal, Department of Medicine, VA Central California Health Care System, University of California, San Francisco, 2615 E Clinton Ave, Fresno, California 93703, USA.
    Department of Medicine, VA Central California Health Care System, University of California, San Francisco, San Francisco, California, USA
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      Anemia is common in patients with chronic kidney disease (CKD) and results from the dysregulation of iron metabolism and erythropoiesis. Hepcidin is a key regulator of iron availability and leads to iron sequestration during the state of iron repletion. Decreases in the level of hepcidin in the presence of hypoxia and/or iron limitation allow for greater iron availability for erythropoiesis. However, kidney excretion of hepcidin decreases as the severity of CKD increases, whereas production of hepcidin is increased under inflammatory conditions often present in patients with CKD, both of which contribute to anemia. Assessment of iron status is, therefore, essential in the treatment of anemia. However, current laboratory tests for the determination of the adequate supply of iron have many limitations, including diurnal variation in the levels of biomarkers, lack of standardized reference methods across laboratories, and confounding by the presence of inflammation. In addition, the current treatment paradigm for anemia of CKD can further disrupt iron homeostasis; for example, treatment with erythropoiesis-stimulating agents in the absence of supplemental iron can induce functional iron deficiency. Moreover, supplemental iron can further increase levels of hepcidin. Several novel therapies, including hypoxia-inducible factor prolyl hydroxylase inhibitors and hepcidin inhibitors/antagonists, have shown promise in attenuating the levels and/or activity of hepcidin in anemia of CKD, thus ensuring the availability of iron for erythropoiesis.

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        Evrenzo® (roxadustat) tablets approved in Japan for the treatment of anemia associated with chronic kidney disease in dialysis patients.
        (Available at:)
        Date accessed: November 25, 2020
        • Akebia
        Akebia Therapeutics announces approval of vadadustat in Japan for the treatment of anemia due to chronic kidney disease in dialysis-dependent and non-dialysis dependent adult patients.
        (Available at:)
        • GlaxoSmithKline
        GSK receives first regulatory approval for Duvroq (daprodustat) in Japan for patients with anaemia due to chronic kidney disease.
        (Available at:)
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