The multifaceted role of complement in kidney transplantation. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Biglarnia, Ali-Reza; Huber-Lang, Markus; Mohlin, Camilla; Ekdahl, Kristina; Nilsson, Bo
• Is Part Of: Nature reviews. Volume 14:Issue 12(2018)
• Page Start: 767
• Page End: 781
• Publication Date: 2018-12
• Subjects: Kidneys -- Diseases -- Treatment -- Periodicals; Nephrology -- Periodicals; 616.61005
• DOI: 10.1038/s41581-018-0071-x
• Languages: English
• ISSNs: 1759-5061

Abstract

Abstract Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia–reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HLA incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response. The complement system has a key role in inflammatory reactions that occur before, during and after transplantation. Here, the authors discuss this role and highlight current and future strategies to regulate complement activation and potentially improve outcomes in kidney transplantation. Key points Complement activation in the donor, the graft and the recipient before, during and after transplantation is a major cause of damage to the kidney transplant. Ischaemia and subsequent reperfusion of the graft is the most important mechanism that triggers complement activation; reperfusion is generally regarded as the most detrimental phase of the transplantation process. Following transplantation, complement has a role in innate immunological and inflammatory processes that further damage the graft and result in a gradual decrease in its functional mass. Complement-targeted strategies might have a role in optimizing graft quality as well as in the treatment of antibody-mediated rejection, induction of accommodation and modulation of the adaptive immune response. Promising data from preclinical and clinical studies suggest that complement-targeted therapies could potentially become part of the standard of care for kidney transplantation.