The role of hepcidin-25 in kidney transplantation

Background: Hepcidin-25 is a peptide hormone involved in iron absorption and homeostasis and found at increased serum levels in conditions involving systemic inflammation, renal dysfunction, and increased adiposity. Hepcidin may play a role in the pathogenesis of anemia, but its role in kidney transplantation is undefined. Methods: This study enrolled 100 stable patients beyond 12 months after transplantation, from a large single United Kingdom center. Serum hepcidin-25 level, and relevant demographic and laboratory data pertinent to posttransplantation anemia, were measured and collected. Independent predictors of serum hepcidin were evaluated, and the relationship between hepcidin and hemoglobin, assessed. Results: Independent associations were seen between higher hepcidin levels and allograft dysfunction (estimated glomerular filtration rate), increased inflammation (high-sensitivity C-reactive peptide), higher transferrin saturation (a marker of iron stores), and the use of marrow-suppressive medication (P<0.05 for all). Higher fat tissue index (whole-body multifrequency bioimpedance measurement) was also associated with higher hepcidin levels, but this relationship did not persist after adjustment for inflammation (high-sensitivity C-reactive peptide). In turn, inflammation was associated with increased fat tissue index (P=0.01) and male gender (P=0.04). A nonlinear association between serum hepcidin level and hemoglobin was seen, with a progressive fall in hemoglobin as hepcidin levels rose to 100 ng/mL, but little effect thereafter (P=0.009). This association was independent of renal dysfunction and female gender, both of which were also independently associated with a lower hemoglobin level. Conclusions: These results highlight possible mechanisms of hemoglobin reduction in kidney transplantation patients, and the therapeutic opportunities from understanding the role of hepcidin in this context.