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Iron overdose: a contributor to adverse outcomes in randomized trials of anemia correction in CKD

  • Nephrology – Review
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Abstract

Administration of intravenous iron to supplement erythropoiesis stimulating agents (ESAs) has become a common practice in the management of anemia in patients with end-stage renal disease. Randomized clinical trials of anemia correction in this population have shown more adverse outcomes in CKD and ESRD patients assigned to the higher hemoglobin targets. Retrospective analysis of these trials suggests that morbidity is higher in subjects who fail to achieve the designated hemoglobin target and are typically exposed to higher doses of ESAs and iron than those that easily achieve the intended targets. Intravenous iron administration circumvents the natural biologic mechanisms for handling and utilization of iron. There is in vitro and in vivo evidence that intravenous iron preparations can cause oxidative stress, endothelial dysfunction, inflammation, impaired immunity, and renal injury. Since iron overload is known to promote endothelial dysfunction, cardiovascular disease, and immune dysfunction which are the leading causes of premature mortality in CKD and ESRD patients, it is imperative to exercise caution with the use of IV iron preparations in this population. The present review is intended to provide a brief overview of the potential adverse effects of the overzealous use of these agents.

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Acknowledgments

Funding sources include NIH F32DK085965-O1A1 (PVB), UT Southwestern O'Brien Kidney Research Core (NIH P30DK079328), and UT Southwestern Clinical Translational Science Award (NIH UL 1RR024982).

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Authors and Affiliations

  1. Departments of Internal Medicine/Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Peter Van Buren & Xin J. Zhou

  2. Dallas Nephrology Associates, Dallas, TX, USA

    Ruben L. Velez

  3. Division of Nephrology and Hypertension, University of California Irvine, Irvine, CA, USA

    Nosratola D. Vaziri

  4. Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9073, USA

    Xin J. Zhou

  5. Division of Nephrology and Hypertension, University of California Irvine Medical Center, Suite 400, City Tower, 101 City Drive, Orange, CA, 92868, USA

    Nosratola D. Vaziri

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  1. Peter Van Buren
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  2. Ruben L. Velez
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  3. Nosratola D. Vaziri
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  4. Xin J. Zhou
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Correspondence to Nosratola D. Vaziri or Xin J. Zhou.

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Van Buren, P., Velez, R.L., Vaziri, N.D. et al. Iron overdose: a contributor to adverse outcomes in randomized trials of anemia correction in CKD. Int Urol Nephrol 44, 499–507 (2012). https://doi.org/10.1007/s11255-011-0028-5

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