Background: Intravenous (IV)
iron is widely used to treat
anemia in
chronic kidney disease patients. Previously,
iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV
iron on complement activation in-vivo, and whether this subsequently induces
inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received
iron sucrose or
ferric carboxymaltose, based on physicians' choice. Plasma samples were collected prior to and 1 h after completion of IV
iron infusion. The dialysis group received
iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive
hemodialysis sessions, one with and one without IV
iron. Finally, plasma levels of MBL, C1q,
properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV
iron by 32%, while levels of
factor D and MBL significantly dropped. Subgroup analysis demonstrated that
iron sucrose induced complement activation whereas
ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV
iron, while
factor D levels significantly fell. Furthermore, the relative decrease in
factor D by IV
iron correlated significantly with the relative increase in sC5b-9 by IV
iron. MPO levels rose significantly during the dialysis session with IV
iron, but not in the session without
iron. Moreover, the relative increase in MPO and sC5b-9 by IV
iron correlated significantly. PTX3 levels were not affected by IV
iron. Conclusions:
Iron sucrose but not
ferric carboxymaltose, results in complement activation possibly via the
lectin and alternative pathway partially mediating oxidative stress but not
inflammation.