Next-Generation Biomarkers for Iron Status

Iron is needed for oxygen transport, muscle activity, mitochondrial function, DNA synthesis, and sensing of hypoxia. The hierarchical master determinant of dietary iron absorption and iron distribution within the body is the peptide hormone hepcidin. Hepcidin itself is regulated by a combination of signals derived from iron stores, inflammation, and erythropoietic expansion. Iron deficiency and iron deficiency anemia are common and important conditions that can be treated with iron preparations. However, other factors besides iron deficiency can cause anemia, especially inflammation, which responds poorly to iron treatment, and inherited disorders of red blood cells, which are associated with accumulation of excess pathogenic iron. Assessment of iron status is challenging, and indices such as serum ferritin, soluble transferrin receptor, and zinc protoporphyrin have specific weaknesses. Moreover, a diagnosis of iron deficiency or iron deficiency anemia is most useful if the diagnosis also leads to effective treatment. Low levels of hepcidin allow iron absorption and effective iron incorporation into red blood cells. The best 'biomarker' to guide treatment may therefore be the physiological 'determinant' of iron utilization. Iron is also important in transplantation medicine and influences clinical outcome of arterial pulmonary hypertension; here too, biomarkers including hepcidin may be useful to actively and beneficially manage iron status.