Hempel, J.C. (Julia Cordelia) (2014) An In Vitro Analysis of the Effects of Parenteral Iron Preparations on Complement Activation Levels. thesis, Medicine.
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Abstract
Background: Anaemia related to CKD is treated with erythropoiesis stimulating-agents complemented with IV iron supplementation. All currently marketed IV iron preparation have been linked to life-threatening anaphylactic-like drug reaction out of which an unknown percentage seems to be complement rather than IgE mediated. Chronic side effects of IV iron preparations are partially resulting from increased ROS generation and oxidative stress and possibly direct, less well understood effects. One of the results is changed mRNA and protein expression in the kidney. Aim: Purpose of this study was to establish a reliable ELISA-based in vitro model to compare the effect of different iron preparations on complement activation in the three complement pathways. With this, a more thorough understanding of complement in acute drug reaction can be attained. Furthermore, cultured endothelial and epithelial cells were exposed to iron sucrose and changes in C3 production as indicator of local complement production were analysed in order to begin to define the role of complement in chronic adverse effects of IV iron supplementation. Findings: Out of six tested IV iron preparations only Venofer and its generic drug (iron sucrose) modulated complement activation. The effects were strongest on the classical pathway, less on the MBL pathway and there was no effect on complement activation via the alternative pathway. Strikingly, physiological (low) iron sucrose doses caused a significant increase in complement activation indicated by C5b-9 generation and increased concentrations resulted in significantly reduced amounts of C5b-9 generation. Also, in podocytes, but not proximal renal tubular cells C3 generation and excretion were affects. Conclusion: Our in vitro setting showed that iron sucrose, but none of the other iron preparations, has the potential to increase or decrease complement activity depending on concentration. Additionally, iron sucrose can also affect local renal C3 production by podocytes. Taken together, it can be stated that complement activation modulation at different levels plays a role in overall adverse effects of parenteral iron administration and mechanisms need to be more closely investigated.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Seelen, Dr. M. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:03 |
| Last Modified: | 25 Jun 2020 11:03 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2306 |
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