Differential Pharmacokinetics of Liver Tropism for Iron Sucrose, Ferric Carboxymaltose, and Iron Isomaltoside: A Clue to Their Safety for Dialysis Patients

Abstract

Anemia is a major complication of end-stage kidney disease (ESKD). Erythropoiesis-stimulating agents and intravenous (IV) iron are the current backbone of anemia treatment in ESKD. Iron overload induced by IV iron is a potential clinical problem in dialysis patients. We compared the pharmacokinetics of liver accumulation of iron sucrose, currently used worldwide, with two third-generation IV irons (ferric carboxymaltose and iron isomaltoside). We hypothesized that better pharmacokinetics of newer irons could improve the safety of anemia management in ESKD. Liver iron concentration (LIC) was analyzed in 54 dialysis patients by magnetic resonance imaging under different modalities of iron therapy. LIC increased significantly in patients treated with 1.2 g or 2.4 g IV iron sucrose (p < 0.001, Wilcoxon test), whereas no significant increase was observed in patients treated with ferric carboxymaltose or iron isomaltoside (p > 0.05, Wilcoxon-test). Absolute differences in LIC reached 25 µmol/g in the 1.2 g iron sucrose group compared with only 5 µmol/g in the 1 g ferric carboxymaltose and 1 g iron isomaltoside groups (p < 0.0001, Kruskal–Wallis test). These results suggest the beneficial consequences of using ferric carboxymaltose or iron isomaltoside on liver structure in ESKD due to their pharmacokinetic ability to minimize iron overload.