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Parenteral Iron Compounds: Potent Oxidants but Mainstays of Anemia Management in Chronic Renal Disease

Fred Hutchinson Cancer Research Center and the Department of Medicine, University of Washington, Seattle, Washington

Address correspondence to: Dr. Richard A. Zager, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N; Room D2–190, Seattle, WA 98109. Phone: 206-667-6222; Fax: 206-667-6519; E-mail: dzager{at}fhcrc.org

Ferric iron (Fe)–carbohydrate complexes are widely used for treating Fe deficiency in patients who are unable to meet their Fe requirements with oral supplements. Intravenous Fe generally is well tolerated and effective in correcting Fe-deficient states. However, the complexing of Fe to carbohydrate polymers does not block its potent pro-oxidant effects; systemic free radical generation and, possibly, tissue damage may result. The purpose of this review is to (1) underscore the capacity of currently used parenteral Fe formulations to induce oxidative stress, (2) compare the severity of these oxidant reactions with those that result from unshielded Fe salts and with each other, and (3) speculate as to the potential of these agents to induce acute renal cell injury and augment systemic inflammatory responses. The experimental data that are reviewed should not be extrapolated to the clinical setting or be used for clinical decision making. Rather, it is hoped that the information provided herein may have utility for clinical hypothesis generation and, hence, future clinical studies. By so doing, a better understanding of Fe's potential protean effects on patients with renal disease may result.

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