Abstract
Our understanding of the pathophysiology of the anaemia of chronic kidney disease (CKD) has improved considerably in the last decade with the discovery of the iron regulatory peptide hepcidin. Reduced clearance of hepcidin and the presence of a chronic inflammatory state contribute to elevated hepcidin levels in kidney disease. The recent discovery of the various factors and signalling pathways regulating hepcidin has opened up an exciting avenue for research into the development of newer agents that could treat anaemia of CKD. This review highlights our current understanding of iron metabolism in health, the regulators of hepcidin, issues associated with the current available therapies for the treatment of anaemia in CKD and potential novel therapies that could be available in the near future targeting the various factors that regulate hepcidin.
Highlights
Anaemia of chronic kidney disease (CKD) is widely prevalent in patients with renal impairment and is associated with significant morbidity and mortality [1, 2]
Hepcidin is regulated by a number of factors including iron status, inflammation, erythropoiesis and hypoxia, which are often affected by kidney disease
Iron metabolism is tightly regulated by the hormone hepcidin which is highly expressed by hepatocytes and at lower levels in other tissues including the kidneys [9]
Summary
Anaemia of chronic kidney disease (CKD) is widely prevalent in patients with renal impairment and is associated with significant morbidity and mortality [1, 2]. Deficient erythropoietin (EPO) production and reduced bioavailability of iron lead to absolute or functional iron deficiency anaemia. An iron regulatory protein produced in the liver by hepatocytes, plays an important role in iron metabolism by regulating iron absorption from the duodenum and iron release from macrophages by interacting with, and inactivating, ferroportin—the iron transport protein [3]. Hepcidin is regulated by a number of factors including iron status, inflammation, erythropoiesis and hypoxia, which are often affected by kidney disease
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