Intravenous iron dose and mortality in hemodialysis patients

To the Editor: There is an important misunderstanding evident in the commentary by Weiss and Kronenberg1 addressing our article2 describing an association between high-dose intravenous iron and mortality in hemodialysis patients. The editorialists state that ‘patients receiving higher dosages of iron also received higher dosages of erythropoiesis-stimulating agent (ESA), pointing to bone marrow hyporesponsiveness. It is therefore also conceivable that higher ESA rather than increased iron dosages contribute to mortality in such subjects …’.1 As shown in Table 2 of the manuscript, however, even after adjustment for ESA dose and hemoglobin concentration, average monthly intravenous iron doses 400 mg/month were associated with significantly increased mortality compared with the most common doses of 100–199 mg/month (hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.0–1.28) and intravenous iron doses 300 mg/month were associated with significantly increased mortality compared with doses <300 mg/month (HR 1.10; 95% CI 1.03–1.17).2 It is therefore incorrect to ascribe to concomitant ESA administration the observed mortality risk associated with intravenous iron prescription. Also, the iron-associated mortality hazard ratios remained of similar magnitude and significance following further adjustment for transferrin saturation and serum ferritin concentration—it does not appear that iron dose was merely a reflection of inflammation as a proximate factor related to mortality. We reiterate our contention that well-powered clinical trials to evaluate the safety of different intravenous iron dosing strategies are urgently needed; we are pleased that the editorialists agreed on this point.