Complement activation in renal transplantation: from donor to recipient

PhD ceremony: Mr. J. Damman, 11.00 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Complement activation in renal transplantation: from donor to recipient

Promotor(s): prof. R.J. Ploeg

Faculty: Medical Sciences

 

Kidney transplantation has become the first choice of treatment for patients with end-stage renal disease, but due to donor organ shortage, patients on the waiting list are still dying. Most kidneys that are transplanted are derived from brain-dead donors. Kidneys from brain-dead donors show inferior transplant outcomes compared to kidneys derived from living donors. In brain-dead donors, local renal and systemic immune activation occurs and is, at least in part, responsible for the pathogenesis of renal injury of kidney grafts to-be. The complement system is part of the innate immune system and has previously been shown to be involved in the course of renal ischemia-reperfusion injury and allograft rejection. This thesis shows that a significant part of the brain death induced immune activation can be ascribed to local and systemic complement activation which is associated with reduced renal allograft outcome in the recipient. We found that targeting complement activation in brain-dead donors significantly improves renal function after transplantation in the recipient. In addition, it was found that genetic variation in the complement C3 gene of cardiac death donor kidneys protects the allograft against primary non-function in the recipient. In humans, randomized clinical trials have to explore whether complement inhibition in deceased donors, as well as the recipient, will improve renal allograft outcome after kidney transplantation.