Iron Sucrose Impairs Phagocytic Function and Promotes Apoptosis in Polymorphonuclear Leukocytes

Abstract

<b><i>Background:</i></b> With the recent implementation of bundling reimbursement policy, the use of intravenous (IV) iron preparations for the management of anemia in the end-stage renal disease (ESRD) population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of polymorphonuclear leukocytes (PMNs) against <i>Escherichia coli</i>. These preparations consist of an elemental iron core and a carbohydrate shell. In addition to the iron core, the carbohydrate shell may affect PMNs. We therefore examined the effect of iron sucrose, a commonly used preparation, on phagocytic capacity of PMNs from a group of normal individuals against Gram-positive <i>(Staphylococcus aureus)</i> and Gram-negative <i>(E. coli)</i> bacteria. <b><i>Methods:</i></b> Iron sucrose was added to heparinized blood samples at pharmacologically-relevant concentrations and incubated for 4 and 24 h at 37°C to simulate in vivo condition. Blood samples mixed with equal volume of saline solution served as controls. To isolate the effects of the carbohydrate shell, blood samples were co-treated with the iron chelator, desferrioxamine. <b><i>Results:</i></b> Iron sucrose caused significant PMN apoptosis and dose-dependent suppression of phagocytic function against both Gram-positive and Gram-negative bacteria. These abnormalities were prevented by desferrioxamine which precluded contribution of the carbohydrate shell to the PMN dysfunction. <b><i>Conclusions:</i></b> At pharmacologically-relevant concentrations, iron sucrose promotes apoptosis and inhibits phagocytic activities of PMNs. The deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell, and as such may be shared by other IV iron preparations.

High Ferritin Level and Malnutrition Predict High Risk of Infection-Related Hospitalization in Incident Dialysis Patients: A Japanese Prospective Cohort Study

“…Findings from an in vitro study using serum samples collected from hemodialysis patients suggest that non-transferrin-bound iron observed in serum after IV iron was positively associated with bacterial growth [19]. Moreover, in a challenge test with healthy subjects, iron supplementation suppressed the phagocytic function of leukocytes against both gram-negative and gram-positive bacteria and induced cell apoptosis [20]. Recently, it was reported that a high serum ferritin level was associated with increased mortality in Japanese hemodialysis patients [17].…”

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…Iron administration deteriorates phagocytic function in gram-positive and gram-negative bacteria and induces apoptosis in polymorphonuclear neutrophil leukocytes [141]. Iron is also necessary for the proliferation of bacteria [142], and for this reason, the possibility of an association between iron administration and the proliferation of bacteria has been raised [143].…”

Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5

“…Intravenous iron therapy may also entail a number of unwanted side-effects and long-term consequences including promotion of atherosclerosis, cardiovascular events, infections or cancer [11-14]. …”