High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity.
BACKGROUND
Iron is essential for the formation of hemoglobin. During long-term treatment with human recombinant erythropoietin (rhEPO), the majority of end-stage renal disease (ESRD) patients will not respond adequately to rhEPO unless substituted with intravenous iron. However, concern exists about possible detrimental effects of parenteral iron on cellular host defense and iron-mediated increments of oxidative stress.


METHODS
We analyzed phagocytic functions of polymorphonuclear leukocytes (PMN) isolated from 20 ESRD patients on peritoneal dialysis in response to 300 mg of iron sucrose or placebo administered intravenously over two hours in a randomized, double-blind manner. We evaluated Fc gamma R-dependent phagocytosis and killing (primary outcome variable) of opsonized Escherichia coli, Fc gamma R-dependent oxidative burst capacity, and complement receptor 3 (CR3, Mac1, CD11b/CD18)/tumor necrosis factor alpha (TNFalpha)-mediated release of bactericidal lactoferrin before, during, one hour, and two days after administration.


RESULTS
The absolute count and the percentage of E. coli killed by PMN of iron sucrose-treated peritoneal dialysis patients decreased significantly over time in comparison to placebo-treated patients (F = 3.48, df = 4, P = 0.008; F = 3.99, df = 4, P = 0.006, respectively). All secondary outcome variables were not different between both groups over time.


CONCLUSIONS
Killing capacity of PMN isolated from ESRD patients decreases in response to high-dose parenteral iron sucrose, possibly in part explaining reported higher hospitalization rates and lower survival rates of dialysis patients receiving frequent and high-dose parenteral iron.
Deicher
Robert
R
Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Allgemeines Krankenhaus der Stadt Wien, Vienna, Austria. robert.deicher@nephro.imed3.akh-wien.ac.at
Ziai
Farzad
F
Cohen
Gerald
G
Müllner
Marcus
M
Hörl
Walter H
WH
D000740:Anemia / Q000188:drug therapy* / Q000276:immunology; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010530:Peritoneal Dialysis; D010587:Phagocytosis / Q000187:drug effects; D011446:Prospective Studies; D016897:Respiratory Burst / Q000187:drug effects
D005290:Ferric Compounds; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid