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

Abstract

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.

Keywords

• chronic kidney disease
• ferric derisomaltose
• intravenous iron
• iron deficiency
• oxidative stress