Am J Kidney Dis 2010;55:726-741.

Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with lower quality of life and higher risk of adverse outcomes, including cardiovascular disease and death. Anemia management in patients with CKD currently revolves around the use of erythropoiesis-stimulating agents and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of erythropoiesis-stimulating agents are used and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many patients with CKD, as with patients with other chronic inflammatory diseases, poor absorption of dietary iron and the inability to use the body’s iron stores contribute to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by increased levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings.

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“Hücreler tipine göre demiri farklı yollardan alırlar. Diyet demiri enterosit tarafından apikal tarafta bulunan DMT1 ile alınırken, makrofajlar önce fagosite ettikleri sirküle eden yaşlı eritrositlerdeki hemoglobinden demir alırlar. Eritrosit lizisi ile açığa çıkan hemoglobinden hemoksijenaz ve biliverdin redüktaz ile demir ve bilirubin oluşur..
Makrofajların vakuolar membranlarından demir transportu gene DMT1 ile olmaktadır. Makrofajlarda açığa çıkan, demir ya tekrar organizmada dolaşan demir olması için makrofaj ferroportini ile plazmaya verilmekte ya da makrofaj içinde ferritin şeklinde depolanmaktadır. Ferroportin enterositte olduğu gibi hücrenin tek demir atıcısıdır. Makrofajdan demir plazmaya verilirken transferine yüklenebilmesi için gene FeIII şekline getirilmeli okside edilmelidir. Bu oksidasyon ve tansferrine yüklenme içinde plazmada bakıra bağlı ferrioksidaz olan ve karaciğerde sentezlenen seruloplazmin rol almaktadır. Hepatositlerin demir alımı TfR1 ve TfR2 ile olur. Hepatositler portal dolaşımdan aldıkları demiri depolarlar ve gerektiğinde ferroportin yolu ile tekrar dolaşıma verirler.”

Blood. 2003;102:783-788

Human hepcidin, a 25–amino acid peptide made by hepatocytes, may be a new mediator of innate immunity and the long-sought iron-regulatory hormone. The synthesis of hepcidin is greatly stimulated by inflammation or by iron overload. Evidence from transgenic mouse models indicates that hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from macrophages. The key role of hepcidin is confirmed by the presence of nonsense mutations in the hepcidin gene, homozygous in the affected members, in 2 families with severe juvenile hemochromatosis. Recent evidence shows that deficient hepcidin response to iron loading may contribute to iron overload even in the much milder common form of hemochromatosis,from mutations in the HFE gene. In anemia of inflammation, hepcidin production is increased up to 100-fold and this may account for the defining feature of this condition, sequestration of iron in macrophages. The discovery of hepcidin and its role in iron metabolism could lead to new therapies for hemochromatosis and anemia of inflammation.