Hepcidin and Anemia in Surgical Critical Care: A Prospective Cohort Study*

Abstract

OBJECTIVE: Because anemia of inflammation is common in ICU patients and hepcidin is the key regulator of iron homeostasis, we examined time-dependent changes in hepcidin, erythropoietin, iron, and inflammatory markers in surgical ICU patients with anemia. DESIGN: Prospective single-center clinical noninterventional study. SETTING: Surgical ICUs; U.S. university hospital. PATIENTS: One hundred surgical adult ICU patients. MEASUREMENTS AND MAIN RESULTS: Time-dependent changes in serum hepcidin, hematologic, and erythropoietic studies were performed on ICU admission and at serial time-points through day 28, and correlated with hematologic and iron parameters and inflammatory response. Median serum hepcidin levels were significantly increased at ICU admission and decreased over time (144-36 ng/mL; p < 0.0001). Despite increased reticulocyte counts (1.3-2.9%), mean serum erythropoietin levels remained low (29-44 mU/mL) and hemoglobin did not significantly change. Hepcidin was positively correlated with RBC transfusion, C-reactive protein, interleukin-6, ferritin, and negatively correlated with iron, total iron binding capacity, transferrin, and reticulocyte response. Hepcidin did not correlate with tumor necrosis factor-α serum concentrations. Regression analyses confirmed that ferritin, C-reactive protein, and reticulocyte number were predictive of same-day hepcidin; hepcidin and C-reactive protein were predictive of same-day reticulocyte count. CONCLUSIONS: Hepcidin serum concentrations are markedly increased on ICU admission, and decrease significantly over the course of the ICU stay (28 d). Decreased hepcidin concentrations are associated with increased reticulocyte response and decreased inflammatory response reflected by decreased interleukin-6 and C-reactive protein concentrations, but not with anemia resolution.