BACKGROUND: Anemia is inevitable as chronic kidney disease (CKD) advances. With the advent of erythropoietin-stimulating agents (ESAs), considerable improvement has been achieved in the management of anemia. However, some patients show a reduced response to ESAs. METHODS: Many factors affect the response to ESA treatment. CKD is now considered as an inflammatory disorder and this understanding led to the recognition of the central role of inflammation in ESA resistance. Inflammation is related to untoward outcomes, including atherosclerosis and anemia, in the CKD population. Furthermore, recognition of deleterious effects of proinflammatory markers at different levels of erythropoiesis led to a change in the name of 'anemia of chronic disease' to anemia of inflammation. RESULTS: The discovery of hepcidin as the major controller of iron metabolism in anemia of inflammation answered many questions regarding the interaction of erythropoietin, iron and bone marrow. Hepcidin production in the liver is driven by three major factors: inflammation, iron overload and anemia/hypoxia. Hepcidin levels are increased in patients with CKD due to the interaction of many factors; a comprehensive understanding of these pathways is thus critical in the effort to alleviate anemia of inflammation and ESA resistance. CONCLUSION: In this review, we discussed the epidemiology, determinants and consequences of anemia of inflammation in CKD patients with special emphasis on the central role of hepcidin along with molecular pathways driving its production.
BACKGROUND:Anemia is inevitable as chronic kidney disease (CKD) advances. With the advent of erythropoietin-stimulating agents (ESAs), considerable improvement has been achieved in the management of anemia. However, some patients show a reduced response to ESAs. METHODS: Many factors affect the response to ESA treatment. CKD is now considered as an inflammatory disorder and this understanding led to the recognition of the central role of inflammation in ESA resistance. Inflammation is related to untoward outcomes, including atherosclerosis and anemia, in the CKD population. Furthermore, recognition of deleterious effects of proinflammatory markers at different levels of erythropoiesis led to a change in the name of 'anemia of chronic disease' to anemia of inflammation. RESULTS: The discovery of hepcidin as the major controller of iron metabolism in anemia of inflammation answered many questions regarding the interaction of erythropoietin, iron and bone marrow. Hepcidin production in the liver is driven by three major factors: inflammation, iron overload and anemia/hypoxia. Hepcidin levels are increased in patients with CKD due to the interaction of many factors; a comprehensive understanding of these pathways is thus critical in the effort to alleviate anemia of inflammation and ESA resistance. CONCLUSION: In this review, we discussed the epidemiology, determinants and consequences of anemia of inflammation in CKDpatients with special emphasis on the central role of hepcidin along with molecular pathways driving its production.
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