Iron Overload in Renal Transplant Patients: The Role of Hepcidin and Erythropoietin

Abstract

Renal transplant patients may present important serum iron overload (IO), which can persist for long periods after transplantation, but its mechanisms are not fully understood. We raised the hypothesis that post-transplant hypererythropoietinemia might induce reduction in serum hepcidin, favoring iron absorption. The aims of this study were to determine the prevalence of IO and associated factors in transplant patients and to evaluate erythropoietin and hepcidin levels in patients with and without IO. A total of 168 patients were included, with a median time of dialysis and transplantation of 28 and 65 months, respectively. Most patients (85%) received large amounts of parenteral iron (3600 mg iron) during the dialysis period. Median ferritin was 427 ng/mL, and transferrin saturation was 33%. IO was present in 26 patients (15%). A comparison of patients with and without IO showed a predominance of male and nonwhite patients in the former group (P < .001 and .002, respectively). The total amount of iron used before transplantation and hemoglobin levels were higher in the group with IO (P = .023 and .046, respectively). Hepcidin was higher in the group with IO (P < .0001), whereas erythropoietin did not differ between groups. There was no correlation between serum levels of hepcidin and erythropoietin (r = –0.001). In conclusion, factors associated with IO were male sex, higher hemoglobin levels, and the amount of iron received before transplantation. IO was not the result of reduction in hepcidin secondary to hypererythropoietinemia. The elevated levels of serum hepcidin were possibly secondary to IO, mediated by mechanisms that are independent of the hepcidin-erythropoietin axis.