Discovery of hepcidin and elucidation of its mechanism of action and consequences of its upregulation and suppression have unraveled important insight into many hematologic disorders including anemia of CKD.
Disturbances in the regulation of hepcidin contribute to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and nontransfused β-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic kidney disease, chronic inflammatory diseases, some cancers, and inherited iron-refractory iron deficiency anemia.
Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease.
Dysregulation of hepcidin production contributes to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and non-transfused β-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic inflammatory diseases and inherited iron-refractory iron-deficiency anemia.
Embryos with transferrin-a or transferrin receptor 2 (TfR2) deficiency exhibited low levels of hepcidin expression, however anemia, in the absence of a defect in the transferrin pathway, failed to impair hepcidin expression.
Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients.
Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHD may be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization by optimizing anemia management.
Expert opinion: Hepcidin is a key regulator of iron availability and is a potential future therapeutic target for managing anemia that is associated with CKD.
Four variables were independently associated with postoperative kidney injury, for which the beta-coefficients (SE) were: minutes on cardiopulmonary bypass, 0.016 (0.004), p < 0.001; intra-operative hepcidin concentration, 0.032 (0.008), p < 0.001; pre-operative anaemia, 1.97 (0.56), p < 0.001; and Cleveland clinic risk score, 0.88 (0.35), p = 0.005.
Genetic disorders of iron overload of iron-linked anemia can be explained by changes in the level of hepcidin or ferroportin and of the ability of ferroportin to be internalized by hepcidin.
Here we demonstrate that the recently described hepcidin repressor-the serine protease matriptase-2 (encoded by Tmprss6)-is responsible for this repression throughout development, with its deficiency leading to increased hepcidin levels triggering iron deficiency and anemia starting in utero.
However, the regulatory mechanisms of hepcidin expression are multiple, including iron-related parameters, anemia, hypoxia, inflammation and hepatocyte function.
Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients.
In 2001, the discovery of a liver-derived peptide hormone known as hepcidin began revolutionizing our understanding of anemia's relation to a number of inflammatory diseases, including KD.
In a global health context the discovery of hepcidin shines a new light on the world's most prevalent micronutrient problem; iron deficiency and its consequent anemia.