Complement activation in kidney transplantation

Long-term graft survival remains a challenge in kidney transplantation and, due to scarcity of available organs, solutions such as xenotransplantation have been revived; and testing of new agents, including complement-targeting biologicals with potential to improve transplant outcomes, has been enhanced. The complement system plays a critical role in the reaction of the host's immune system to the transplanted foreign kidney. Activation of the complement system is strongly involved in ischemia/reperfusion-mediated injury and rejection of allo- as well as xeno-grafts, and post-transplant recurrence rates are high in kidney diseases linked to complement system dysregulation. Therefore, the precise understanding of the complement activation cascade is important for the development of successful strategies that target complement before and after transplantation. This article compiles the current knowledge on the role of the complement system in kidney transplantation, examines recent developments in the clinical use of complement-targeting therapeutics, and discusses the limitations of these approaches. While the current study results indicate that complement-targeting strategies are still in their early stages, promising findings related to the discovery of new agents encourage the redesign of existing therapeutic approaches and the development of more effective treatments.