Ferroportin inhibition attenuates plasma iron, oxidant stress, and renal injury following red blood cell transfusion in guinea pigs.

Background: Red blood cell (RBC) transfusions result in the sequestration and metabolism of storage-damaged RBCs within the spleen and liver. These events are followed by increased plasma iron concentrations that can contribute to oxidant stress and cellular injury. We hypothesized that administration of a ferroportin inhibitor (FPN-INH) immediately after acute RBC exchange transfusion could attenuate posttransfusion circulatory compartment iron exposure, by retaining iron in spleen and hepatic macrophages.

Study Design And Methods: Donor guinea pig blood was leukoreduced, and RBCs were preserved at 4°C. Recipient guinea pigs (n = 5/group) were exchange transfused with donor RBCs after refrigerator preservation and dosed intravenously with a small-molecule FPN-INH. Groups included transfusion with vehicle (saline), 5 mg/kg or 25 mg/kg FPN-INH. A time course of RBC morphology, plasma non-transferrin-bound iron (NTBI) and plasma hemoglobin (Hb) were evaluated. End-study spleen, liver, and kidney organ iron levels, as well as renal tissue oxidation and injury, were measured acutely (24-hr after transfusion).

Results: RBC transfusion increased plasma NTBI, with maximal concentrations occurring 8 hours after transfusion. Posttransfusion iron accumulation resulted in tubule oxidation and acute kidney injury. FPN inhibition increased spleen and liver parenchymal/macrophage iron accumulation, but attenuated plasma NTBI, and subsequent renal tissue oxidation/injury.

Conclusion: In situations of acute RBC transfusion, minimizing circulatory NTBI exposure by FPN inhibition may attenuate organ-specific adverse consequences of iron exposure.