The Complement System in the Modern Era of Kidney Transplantation: Mechanisms of Injury and Targeted Therapies

Kidney transplantation remains the treatment of choice for patients with end-stage kidney disease. Significant progress has been made over the course of many years to improve both patient and graft outcomes after transplant. Modern immunosuppressive therapy has reduced the rate of acute rejection and resulted in excellent short- and long-term graft survival. Over the past decade or so, we have become more cognizant of the role of the complement in many events related to the transplant process. A myriad of events that include the cause of death in deceased donors, organ procurement and preservation events, cold ischemia time, time to kidney anastomosis, ischemia-reperfusion injury, recipient immunologic response during and after transplantation, immunosuppressive drug toxicity, and recurrence of original disease all have been shown to affect graft survival. The involvement of the complement system and its activation around the time of kidney transplantation increasingly is recognized as a key player affecting long-term graft survival. In this review, we highlight the important role of the complement system at every stage of the kidney transplantation process. We review potential triggers of complement activation in kidney transplant patients and discuss novel therapeutic agents that can inhibit the complement system.