Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children

Abstract

Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important. We studied Gambian children with either postmalarial or nonmalarial anemia, who were given oral iron supplements daily for 30 days. Supplements administered on days 1 and 15 contained the stable iron isotopes 57Fe and 58Fe, respectively, and erythrocyte incorporation was measured in blood samples drawn 14 days later. We investigated how the iron-regulatory hormone hepcidin and other inflammatory/iron-related indices, all measured on the day of isotope administration, correlated with erythrocyte iron incorporation. In univariate analyses, hepcidin, ferritin, C-reactive protein, and soluble transferrin receptor (sTfR) strongly predicted incorporation of 57Fe given on day 1, while hepcidin, ferritin, and sTfR/log ferritin correlated with 58Fe incorporation. In a final multivariate model, the most consistent predictor of erythrocyte isotope incorporation was hepcidin. We conclude that under conditions of competing signals (anemia, iron deficiency, and infection), hepcidin powerfully controls use of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

“…38 Our data show that b-thalassemia carriers have suppressed hepcidin concentrations overall and out of proportion to their iron stores. Hepcidin concentrations predict iron absorption and use, 39 and thus, even moderate suppression of hepcidin, as seen here, can enhance iron absorption. The plausible explanation is that the mild anemia and increase in Epo and erythropoiesis seen in this condition mediate hepcidin suppression.…”

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study

“…Clinicians monitored children's health statuses during sick visits and at routine visits occurring on a biweekly basis during the first 12 months of life and a monthly basis for any follow-up beyond the first year. Children's hemoglobin was measured at sick visits and during routine visits at approximately 3,6,12,18,24,30,36,42, and 48 months of age. Parasitemia by P. falciparum was determined after counting 200 leukocytes on Giemsa-stained thick blood smear of a sample collected by heel or finger prick during child visits.…”

“…The 25-amino acid bioactive isoform of hepcidin was detected in cord blood plasma using the hepcidin-25 (human) EIA kit (Bachem, Bubendorf, Switzerland) as previously described. 24 A dilution series of standard hepcidin-25 was run on each plate with values ranging FIGURE 1. Selection of the study sample.…”

Modern iron replacement therapy: clinical and pathophysiological insights

“…Thus, in a near future baseline hepcidin measurement in IDA could actually help in tailoring iron therapy, by selecting the optimal route of administration in a given individual [25]. This would be particularly useful in certain "difficult" populations, such as the elderly [4] and children in developing countries [80]. An already established major advance in oral iron therapy deriving from hepcidin discovery is related to the administration schedule.…”