Immune damage and repair after vascular injury
Research type
Research Study
Full title
Establishing pre-clinical models of human chronic rejection and repair
IRAS ID
164268
Contact name
Martin Drage
Contact email
Sponsor organisation
Guy's and St Thomas' Foundation NHS Trust
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Allogenic renal transplantation is the treatment of choice for end-stage kidney disease. It offers superior outcomes in terms of both morbidity and mortality when compared to other forms of renal replacement therapy including dialysis. However, despite significant improvements in 1-year survival, the rate of chronic loss after the first year remains substantial and most transplanted organs fail prematurely, before the natural lifespan of the recipient.
The single largest cause of allograft failure remains chronic rejection, an immune-mediated injury involving blood vessels. Rejection episodes result in vascular damage characterised by intimal hyperplasia (IH) and vascular remodelling leading to stenosis, ischaemia, fibrosis and progressive loss of renal function with late failure of the transplanted kidney. Currently there is no way to prevent or adequately treat this problem but all efforts are focussed on modulating recipients' immune responses using enhanced or more specifically targeted immunosuppressive therapies. This strategy is fraught with difficulty due to the significant side effects associated with long-term immunosuppression including severe infection, malignancy and cardiovascular disease, all of which have an adverse impact on morbidity and mortality. It is paramount therefore that improved understanding of how damage occurs and strategies to prevent it continue to be investigated.
The aim of this application is to use human samples to investigate chronic rejection in novel mouse pre-clinical models. It will deliver original insights into the pathology of human chronic rejection and establish a basis for innovative therapeutic strategies.
REC name
London - Hampstead Research Ethics Committee
REC reference
14/LO/2086
Date of REC Opinion
14 Nov 2014
REC opinion
Favourable Opinion