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C5a receptors in renal transplantation

PhD ceremony:Ms M.B. (Maaike) van Werkhoven
When:May 06, 2015
Supervisors:W.J. van Son, prof. dr. J.L. (Jan-Luuk) Hillebrands
Co-supervisors:M.A.J. Seelen, J. Damman
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
C5a receptors in renal transplantation

Although numerous kidney transplantations are performed each year, the average waiting time for a renal allograft in the Netherlands is currently five years due to shortage of donor organs. Since renal transplantation is the first choice of treatment for end-stage renal disease, it is essential that renal transplant recipients benefit from their renal allograft as long as possible. During the last few decades, development of immunosuppressive drugs has greatly improved first-year allograft survival. In order to improve long-term survival rates as well, identification of new therapeutic targets is crucial. The complement system, an important part of the innate immune system, emerges as a promising target to serve this purpose. It is known that the complement system is activated in the brain dead donor and that it is involved in ischemia-reperfusion injury and rejection of renal allografts. However, the role of individual complement components remains to be investigated. The research described in this thesis focuses on the role of two receptors of the complement system, namely C5aR and C5L2, in kidney transplantation. After we determined the exact localization of C5aR and C5L2 in the kidney, we investigated the role of these receptors in the brain dead donor and during ischemia-reperfusion injury of the renal allograft. The results described in this thesis show that inhibition of C5L2 in the brain dead donor and inhibition of both C5aR and C5L2 during ischemia might improve renal allograft survival rates and post-transplant function.