Although
kidney transplantation is the best treatment for
end stage kidney disease, the benefits are limited by factors such as the short fall in donor numbers, the burden of immunosuppression and graft failure. Although there have been improvements in one-year outcomes, the annual rate of graft loss beyond the first year has not significantly improved, despite better
therapies to control the alloimmune response. There is therefore a need to develop alternative strategies to limit kidney injury at all stages along the transplant pathway and so improve graft survival.
Complement is primarily part of the innate immune system, but is also known to enhance the adaptive immune response. There is increasing evidence that complement activation occurs at many stages during
transplantation and can have deleterious effects on graft outcome. Complement activation begins in the donor and occurs again on reperfusion following a period of
ischemia.
Complement can contribute to the development of the alloimmune response and may directly contribute to graft injury during acute and chronic allograft rejection. The complexity of the relationship between complement activation and allograft outcome is further increased by the capacity of the allograft to synthesise
complement proteins, the contribution
complement makes to interstitial
fibrosis and
complement's role in the development of recurrent disease. The better we understand the role played by
complement in kidney transplant pathology the better placed we will be to intervene. This is particularly relevant with the rapid development of
complement therapeutics which can now target different the different pathways of the
complement system. Combining our basic understanding of
complement biology with preclinical and observational data will allow the development and delivery of clinical trials which have best chance to identify any benefit of
complement inhibition.