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The challenge

  • Understanding anaemia of CKD

    Anaemia is a common feature of chronic kidney disease,1 and one of the hallmarks of advanced CKD.2,3

    The prevalence of anaemia increases as CKD progresses, from 42.5% at stage 3b CKD to 83.7% in people with stage 5 CKD.4

    Anaemia is known to be caused by a number of factors, including:1,6-9

    Illustration of kidneys

    Disrupted oxygen sensing in the kidney

    Illustration of red blood cells

    Reduced erythropoietin production

    Illustration of liver

    Chronic inflammation resulting in increased hepcidin levels

    Illustration of blood droplet with arrow

    Iron deficiency

    1_1_HIF mechanism_GIF_CKD

    Inverse relationship between Hepcidin (Hep) and available iron (Fe) and plasma Erythropoetin (EPO) concentration. With inflammation and Hep production red blood cell (RBC) production and Hb decreases.

    As CKD progresses:5
    • EPO production decreases, leading to a reduction in red blood cells and haemoglobin
    • Hepcidin levels are elevated due to inflammation and decreased renal excretion
    • Elevated hepcidin leads to a reduction in absorption, recycling and mobilisation of iron

    CKD, chronic kidney disease; EPO, erythropoietin.

    References

    • Babitt JL, Lin HY. J Am Soc Nephrol. 2012;(10)23:1631-1634.
    • Del Vecchio L, LocateIIi F. Expert Opin Investig Drugs. 2018;27(1):125-133.
    • Koury MJ, Haase VH. Nat Rev Nephrol. 2015;11:394–410.
    • Evans M et al. Clin Kidney J. 2020;13(5):821-827.
    • Locatelli F et al. Am J Nephrol. 2017;45:187-199.
    • Wenger RH, Hoogewijs D. Am J Physiol Renal Physiol. 2010;298:F1287–F1296.
    • Fishbane S, Spinowitz B. Am J Kidney Dis. 2018;71:423–435.
    • Peyssonnaux C et al. Cell Cycle. 2008;7:28–32.
    • Kaplan JM et al. Int J Mol Sci. 2018;19:389.

  • Treatment challenges

    A specialist's view

    The burden of anaemia of CKD and challenges in its management

    What do patients want from their treatment?

    Management of anaemia of CKD can be sub-optimal.1-3

    Treatment of anaemia of CKD is based on iron supplements and ESAs (erythropoiesis-stimulating agents).1

    These treatments target individual factors of anaemia of CKD.

    CKD, chronic kidney disease; ESA, erythropoiesis-stimulating agent.

    References

    • Del Vecchio L, LocateIIi F. Expert Opin Investig Drugs. 2018;27(7):613-621.
    • Guedes M et al. Kidney360. 2020;(1):855-62.
    • Lopes MB et al. Nature Scientific Reports. 2021;11:1784.

  • The need for an alternative treatment option

    Limitations of current therapies have driven a search for alternative treatment options.1

    Advances in the study of CKD-associated anaemia have focused on the pathophysiology of anaemia with the hope of discovering more targeted and physiological therapies.1-4

    The discovery of hypoxia-inducible factors (HIFs) has led to the development of a class of drugs that stimulate erythropoiesis by activating the HIF pathway.1,4,5

    Discover the HIF pathway

    CKD, chronic kidney disease; HIF, hypoxia-inducible factor.

    References

    • Locatelli F et al. Am J Nephrol. 2017;45:187-199.
    • Babitt JL, Lin HY. J Am Soc Nephrol. 2012;(10)23:1631-1634.
    • Koury MJ, Haase VH. Nat Rev Nephrol. 2015;11:394–410.
    • Haase VH. Hemodial Int. 2017;21:S110–S124.
    • Del Vecchio L, LocateIIi F. Expert Opin Investig Drugs. 2018;27(7):613-621.