Complement activation in chronic kidney disease and dialysis

Chronic kidney disease (CKD) is a growing health problem with a prevalence of approximately 10-15% worldwide. Progression of CKD leading to end-stage renal disease requires renal replacement therapy. In the Netherlands, approximately 6500 patients receive dialysis. Although dialysis is a life-saving treatment, the life expectancy and the quality of life of these patients is inferior to the general population. The complement system, the major part of the innate immune system, has been proposed to play a vital role in the inflammatory response induced by dialysis and could be the missing link between high morbidity and mortality and dialysis. In this thesis, we investigated the role of the complement system in different contexts: in healthy, CKD patients and during dialysis. We found that both types of dialysis, hemodialysis and peritoneal dialysis lead to complement activation. In hemodialysis patients, complement activation during the initial minutes of the hemodialysis session was related to the development of future cardiovascular event. Furthermore, in peritoneal dialysis complement activation occurred not only locally, in the peritoneal cavity, but also systemically. We also explored the complement activating ability of intravenous iron formulations, since CKD patients, dialysis dependents or not, commonly receive intravenous iron to control anemia. Finally, we unraveled the influence of age and sex on the complement system in healthy individuals. In conclusion, considering the link between complement activation and cardiovascular disease, targeting the complement system in CKD and dialysis is a potential strategy to improve outcome in these patients.