Impact of iron dextran on polymorphonuclear cell function among hemodialysis patients

Abstract

Polymorphonuclear cell (PMN) dysfunction and the increased use of parenteral iron may be important contributory factors to bacterial infections among patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). We compared the in vitro impact of a commonly used parenteral iron preparation, iron dextran, on PMN function and viability between a group of HD patients with normal iron indices and healthy subjects. Eleven patients with ESRD on HD and 10 healthy subjects were studied. PMN harvested from heparinized blood were incubated with iron dextran (0 - 20 mM) in culture medium (RPMI) for 24 hours at 37 degrees C with 5% CO2 following which function and viability were assessed by flow cytometry using appropriate fluorescent labels. Unstimulated, S. aureus and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated hydrogen peroxide (H2O2) production was significantly higher in PMN unexposed to iron dextran from HD patients compared to those from healthy subjects. Iron dextran had no impact on unstimulated PMN H2O2 production in either group. In the healthy group, the only significant change occurred with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) stimulation, where cells exposed to 0.2 and 2.0 mM iron dextran produced less H2O2 relative to PMN unexposed to iron dextran (p < 0.05). In the HD group, all concentrations of iron dextran significantly attenuated H2O2 production stimulated by S. aureus, fMLP and PMA compared to PMN unexposed to iron dextran. Although PMN phagocytosis decreased with exposure to increasing concentration of iron dextran in both healthy subjects and HD patients, these changes did not achieve statistical significance. No significant changes in PMN viability or apoptosis were seen in either group after exposure to iron dextran. These results indicate that iron dextran, a standard parenteral iron preparation, attenuates PMN function in HD patients with normal iron indices at clinically relevant concentrations. Further studies are required to evaluate and compare the impact of newer preparations of parenteral iron, such as iron sucrose and ferric gluconate, on PMN function.