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Is a high-dose iron regimen safe during kidney dialysis?

A high-dose iron regimen in patients receiving dialysis is a common practice, but limited evidence supports its safety. A recent study evaluated the safety and efficacy of this practice.

Patients undergoing kidney dialysis usually have low iron levels. Up to three grams of iron may be lost in one year through the kidney dialysis circuit. With reduced kidney function, patients also require frequent blood testing. Anemia is a common condition associated with kidney disease. Iron must be supplied intravenously because dietary iron is poorly absorbed in patients with chronic kidney disease.

There is substantial variation between iron regimens prescribed by kidney specialists across the globe. High-dose intravenous iron regimens have been associated with high risks of infection, oxidative stress, calcification of the blood vessels, and blood clots. Nevertheless, a high-dose iron regimen has the benefit of reducing a patient’s need for erythropoiesis-stimulating agents. An erythropoiesis-stimulating agent is the last resort treatment for anemia because of the possible toxic cardiovascular side effects.  Limiting a patient’s exposure to erythropoiesis-stimulating agents and managing side effects of iron supplementation aid in reducing cardiovascular toxicities.

Lack of rigorous evidence on the safety and efficacy of high-dose iron regimens

The lack of rigorous evidence for the safety and efficacy of high-dose iron regimens resulted in different local and international recommendations for iron supplementation during kidney dialysis. A group of researchers from the Department of Renal Medicine at the King’s College Hospital in London, England compared the safety and efficacy of high and low dose iron regimens in patients undergoing kidney dialysis.

The purpose of the study was to compare the combined rate of heart attacks, strokes, hospitalization for heart failure, and death between both intravenous iron regimens in patients undergoing kidney dialysis. The researchers also compared the total doses of erythropoiesis-stimulating agents given to patients in each treatment group. The results of this study were published in the New England Journal of Medicine.

No increase in the rate of infection in the patients receiving high doses

Throughout 50 dialysis sites in the United Kingdom over 54 months, 2141 adults undergoing dialysis treatment were included in the study. Patients were randomly assigned to receive a high-dose or a low-dose iron regimen. The combined rate of episodes of heart attack, stroke, hospitalization for heart failure, and death was similar between both treatment groups. There was no increase in the rate of infection in the high-dose iron regimen group. More doses of an erythropoiesis-stimulating agent were administered to patients receiving the low iron regimen. The side effect rates were also similar between both treatment groups.

The lower rates of cardiovascular effects in the high-iron dose regimen group could be explained by the reduced need for erythropoiesis-stimulating agents. Also, correcting an iron deficiency is also associated with cardiovascular benefits. Nevertheless, there was no increase in the rate of cardiovascular effects with high doses of intravenous iron. The absence of an increased rate of infection in patients receiving high dose intravenous iron was a critical finding. Previous studies have warned about the possibility of increased bacterial growth with high doses of iron. These results show greater benefits over the risks of a high-dose iron regimen.

Future studies should investigate the effects of longer treatment times

The data from this study were collected from only one country; therefore, the results cannot be generalized to dialysis patients worldwide. The trial lasted just four and a half years. Further studies are required to confirm these results across a broader population and over a more extended period.

The safety and efficacy of a high-dose iron regimen demonstrated in this study may pave the way for standardizing iron supplementation in kidney dialysis. Further studies are required to include a diversified population. Longer treatment times must also be studied to confirm the safety profile of a high-dose iron regimen.

Written by Jessica Caporuscio, PharmD

References:

  1. Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis.N Engl J Med. 2018
  2. Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631-4.
  3. Wise, J. High dose iron regimen improves outcomes in dialysis patients, UK study finds. BMJ.2018
Jessica Caporuscio PharmD
Jessica Caporuscio PharmD
Jessica received her Doctorate of Pharmacy from the University of Montreal in July 2014 and she has been working as a community pharmacist in the Greater Toronto Area since March 2015. She has a passion to communicate medical and drug information to her patients and other healthcare professionals. Jessica is also a marathoner and an Ironman triathlete. In her spare time, she is in her kitchen creating healthy recipes for her family.
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