The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia of chronic disease (ACD) in combination, provoked us to pose the question about their reciprocal dependence and relationship with specific biomarkers; namely, soluble transferrin receptor (sTfR), growth differentiation factor 15 (GDF15), hepcidin 25 and zonulin.
In conclusion, we developed a dose-dependent and safe approach for the direct suppression of hepcidin, resulting in prolonged iron mobilization to alleviate iron-restricted erythropoiesis that can address the root cause of ACD.
Hepcidin is the master inducer of iron accumulation during ACD, and its production is mainly regulated by IL-6 and the novel erythroid hormone erythroferrone (ERFE).
Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis, and its inhibition could be a favorable strategy for treating anemia of chronic disease (ACD).
Treating anemia of chronic disease and anemia of chronic kidney disease may be limited by elevated levels of hepcidin and new promising treatments are still in pre-clinical and clinical trial phases.
The anaemia of chronic disease (ACD) results from inflammation-mediated up-regulation of the iron regulatory hormone hepcidin, with the consequent sequestration of iron limiting its availability for erythropoiesis.
We conclude that serum hepcidin levels can predict the hematologic responsiveness to erythropoiesis-stimulating agent therapy in anemia of chronic disease.
Hepcidin, the pivotal regulator of iron metabolism, plays a critical role in multiple diseases including anemia of chronic disease and hemochromatosis.
Misregulation of hepcidin is found in many disease states, such as the anemia of chronic disease, iron refractory iron deficiency anemia, cancer, hereditary hemochromatosis, and ineffective erythropoiesis, such as β-thalassemia.
In this review, we will summarize the role of hepcidin in iron homeostasis, its contribution to the pathophysiology of ACD, and novel strategies that modulate hepcidin and its target ferroportin for the treatment of ACD.
Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity.
Our results suggest that ferroportin expression in inflammatory monocytes is negatively affected by autocrine formation of hepcidin, thus contributing to iron sequestration within monocytes as found in ACD.
We speculated that the adipokine leptin might play a role in regulating iron metabolism in the overweight population because it shares a number of common biological features with IL-6, a major factor in the development of the anemia of chronic disease via its stimulatory actions on the production and release of the iron regulatory hormone hepcidin.
Our data indicate that hypoferremia in ACD may result from downregulation of ferroportin expression by hepcidin and cytokines with subsequent iron retention in monocytes.
Hepcidin is a proposed mammalian host defense peptide that was identified on the basis of its antimicrobial activity, but it was later shown to be a crucial regulator of iron homeostasis and a mediator of the anemia of chronic inflammation.