Evidence for tissue iron overload in long‐term hemodialysis patients and the impact of withdrawing parenteral iron

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background/aims</jats:title><jats:p>Erythropoiesis in long‐term hemodialyzed (<jats:styled-content style="fixed-case">LTH</jats:styled-content>) patients is supported by erythropoietin (r<jats:styled-content style="fixed-case">H</jats:styled-content>u<jats:styled-content style="fixed-case">E</jats:styled-content>po) and intravenous (<jats:styled-content style="fixed-case">IV</jats:styled-content>) iron. This treatment may end up in iron overload (<jats:styled-content style="fixed-case">IO</jats:styled-content>) in major organs. We studied such patients for the parameters of <jats:styled-content style="fixed-case">IO</jats:styled-content> in the serum and in major organs.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients were treated with r<jats:styled-content style="fixed-case">H</jats:styled-content>u<jats:styled-content style="fixed-case">E</jats:styled-content>po (6–8 x 10<jats:sup>3</jats:sup> units × 1–3/wk) and <jats:styled-content style="fixed-case">IV</jats:styled-content> 100 mg ferric saccharate.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 115 patients, 21 had serum ferritin (<jats:styled-content style="fixed-case">SF</jats:styled-content>) > 1000 ng/mL. This group was further analyzed. Their <jats:styled-content style="fixed-case">SF</jats:styled-content> and transferrin saturation (<jats:styled-content style="fixed-case">TSAT</jats:styled-content>) were 2688 ± 1489 ng/mL and 54.2 ± 32.7%, respectively (vs. 125–360 ng/mL and 20–50% in normal controls). Serum hepcidin was 60.1 ± 29.5 n<jats:sc>m</jats:sc> (vs. 10.61 ± 6.44 n<jats:sc>m</jats:sc> in controls) (<jats:italic>P</jats:italic> < 0.001). Nineteen patients had increased malonyldialdehyde, a product of lipid peroxidation, indicating oxidative stress. <jats:styled-content style="fixed-case">T</jats:styled-content>2* <jats:styled-content style="fixed-case">MRI</jats:styled-content> disclosed in 19 of 21 patients moderate to severe <jats:styled-content style="fixed-case">IO</jats:styled-content> in the liver and spleen, in three of eight patients in the pancreas, but in no patient in the heart. After stopping <jats:styled-content style="fixed-case">IV</jats:styled-content> iron for a mean of 12 months, while continuing <jats:styled-content style="fixed-case">rHuE</jats:styled-content>po, the mean <jats:styled-content style="fixed-case">SF</jats:styled-content> decreased in 11 patients to 1682 ng/mL and the mean <jats:styled-content style="fixed-case">TSAT</jats:styled-content> decreased to 28%, whereas hemoglobin did not change indicating that tissue iron was utilized.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>High <jats:styled-content style="fixed-case">SF</jats:styled-content> correlates with <jats:styled-content style="fixed-case">IO</jats:styled-content> in the liver and spleen, but not in the heart.</jats:p></jats:sec>