Year: 2014
Type: review
Abstract: Improvements in clinical care and immunosuppressive medications have positively affected outcomes following kidney transplantation, but graft survival remains suboptimal, with half-lives of approximately 11 years. Late graft loss results from a confluence of processes initiated by ischemia-reperfusion injury and compounded by effector mechanisms of uncontrolled alloreactive T cells and anti-HLA antibodies. When combined with immunosuppressant toxicity, post-transplant diabetes and hypertension, and recurrent disease, among other factors, the result is interstitial fibrosis, tubular atrophy, and graft failure. Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. Complement activation and function affects allograft injury at essentially every step. These fundamental new insights, summarized herein, provide the foundation for testing the efficacy of various complement antagonists to improve kidney transplant function and long-term graft survival.
DOI: 10.1172/jci72273
Authors: Paolo Cravedi, Peter S. Heeger
Institution: Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2168465695