The comparative effects of intravenous iron on oxidative stress and inflammation in patients with chronic kidney disease and iron deficiency: a randomized controlled pilot study

BACKGROUND: Concerns exist regarding the pro-oxidant and inflammatory potential of intravenous (IV) iron due to labile plasma iron (LPI) generation. This IRON-CKD trial compared the effects of different IV irons on oxidative stress and inflammation. METHODS: In this randomized open-label explorative single-center study in the United Kingdom, non-dialysis-dependent chronic kidney disease (CKD) patients with iron deficiency were randomized (1:1:1:1) to receive a single infusion of 200 mg iron dextran, or 200 mg iron sucrose (IS), or 200 mg or 1,000 mg ferric derisomaltose (FDI) and were followed up for 3 months. The primary outcomes measured were induction of oxidative stress and inflammation. Secondarily, efficacy, vascular function, quality of life, and safety were monitored. RESULTS: Forty patients were enrolled. No significant rise in oxidative stress existed, regardless of preparation or dose. There was a significant rise in LPI with 1,000 mg FDI at 2 hours that normalized within a week, not impacting oxidative stress or inflammation. A delayed rise in C-reactive protein was noted with IS. High-dose FDI produced a sustained serum ferritin increase (mean ± standard error of the mean of predose: 69.1 ± 18.4 μg/L, 3 months: 271.0 ± 83.3 μg/L; p = 0.007). Hemoglobin remained stable throughout. No adverse drug reactions were recorded during the study. CONCLUSION: A single dose of IV iron in CKD patients does not trigger oxidative stress or inflammation biomarkers. Third-generation IV irons have a reassuring safety profile, and high-dose FDI produced a sustained serum ferritin rise and more efficient iron repletion, with no significant pro-oxidant or inflammatory signals when compared to a lower dose and other IV irons.