Jul
2012

Iron sucrose impairs phagocytic function and promotes apoptosis in polymorphonuclear leukocytes.

Ichii H, Masuda Y, Hassanzadeh T, Saffarian M, Gollapudi S, Vaziri ND
Am J Nephrol 2012;36:50-57.
NATA Rating :
Review by : M. Muñoz
NATA Review

In this study, Ichii et al. demonstrated both increased apoptosis and impaired phagocytic function of polymorphonuclear leucocytes incubated with pharmacological doses of iron sucrose (IS; 20, 100, and 200 mg/L) for 4 and 24 h at 37°C. This deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell. Although the study methodology is solid, and the results are valid, the authors fail in interpreting these findings clinically as mentioned in the study limitations (this study is supposed to be a patient-oriented, translational research):

1. The study was conducted with blood samples from healthy individuals rather than from end-stage renal disease (ESRD) patients. In ESRD patients, the most common dose of IS is 100 mg, which is equivalent to the lower concentration in this study (20 mg/L). This iron sucrose concentration affects PMNs apoptosis and phagocytic function only marginally (see figures 1-3).

2. The study was conducted in a closed system in which IS concentrations remain constant throughout the study period. Therefore, it does not mimic in vivo conditions, where IS is rapidly taken up by reticuloendothelial system macrophages (plasma half-life of IS is 4-6 hours).

3. While some studies of ESRD patients on dialysis have found an increased susceptibility to infections after intravenous (IV) iron administration [1,2], others have not [3]. A review of oral versus IV iron in non-hemodialysis renal failure patients found no evidence for an increase in infection rates in the IV iron group [4]. Several observational studies and a randomized controlled trial evaluating preoperative IV iron supplementation in patients undergoing lower limb arthroplasty or hip fracture surgery showed no increased rates of infectious complications in patients treated with IV iron compared with those receiving standard treatment [5]. A large placebo-controlled study of IV iron in patients with chronic heart failure [6] has shown clear clinical benefits, but no increase in infections in the group treated with IV iron.

4. Therefore, although data from this study confirm the concerns about the adverse effects of IV iron on host defense mechanisms against bacterial and fungal infection (especially when given at high, sustained doses), it would seem that, when used in the usual doses and within existing guidelines, the benefits of IV iron therapy are substantial in medical and surgical patients, and the risks are small.

– Manuel Muñoz

References

1. Sirken G et al. Clin Nephrol 2006;66:348-56.

2. Kalantar-Zadeh K et al. Adv Chronic Kidney Dis 2009;16:143-51.

3. Bansal A et al. Am J Ther 2012; Jul 23 [Epub ahead of print].

4. Liles AM. Am J Health Syst Pharm 2012;69:1206-11.

5. Muñoz M et al. Blood Transfus 2012;10:8-22.

6. Anker SD et al. N Engl J Med 2009;361:2436-48.