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Presentation
The network and its partners
History of transplantation  |
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Causes of late graft loss
LATE GRAFT LOSS : MAJOR ADVANCES SINCE 50 years in SHORT TERM GRAFT SURVIVAL
Survival of kidney graft has greatly improved since the first kidney transplant in 1952 at the Necker's Hopital between two genetically different persons. The average term for a graft survival was 3 weeks in 1952 compared to about fifteeen years nowadays.
These improvements are directly linked to immunosuppressive therapies, to antilymphocytic serum use in the 70's, to the ciclosporine discovery in the 80's, then to the last generation of immusuppressive drugs at the end of the 90's, which have hugely reduced the impact of acute rejection - from 50% in 1995 from less than 20% in 2005. Preservation liquids, new drugs with a cardiovascular aim and new anti-virus drugs which reduce viral infection particularly harsh under immunosuppressor treatment have also highly contributed to graft survival duration and patient survival.
This graft survival curve shows some improvement during the initial time (see box text). On the contrary, decrease of graft survival curve stays still for 20 years (Source: Biomédecine Agency)
IN 2008 Late graft loss is the first cause of failure in kidney transplantation
Thanks to tremendous results obtained in short-term grafts, late graft loss has become the first cause of failure in kidney transplantation. It results from a multi-factorial phenomenom which attack the graft for many years.
- Immune factors grouped together under chronic rejection phenomenon.
- Non immune factors, linked to the donor, to ischaemia/reperfusion lesions, to kidney toxicity of immunosuppression medication, to arterial hypertension, to recurrence of kidney diseases on the graft.
ORGAN SHORTAGE leads towards THE use of marginal grafts
Improving factors for graft survival are all the more important because of the organ shortage situation: although the number of annual kidney transplants is increasing (2900 transplants in 2009), graft supply is inferior to the need and the number of patients on the waiting list is growing (diagram R1). This lack of organs heads toward transplantation of lower quality regarding organs, organs coming from aged donors, whose life expectancy is limited (diagram P III). The use of perfusion machines, the development fo new preservation liquids and the use of new non nephrotoxic immunosuppressive drugs are necessary to reduce as much as possible kidneys attacks after transplantation.
THE RATIO OF IMMUNIZED PATIENTs with high immune risks is growing
Blood transfusions, pregnancies and previous transplants immunize recipients agains the HLA system of potential donors. These immunized recipients show a high risk to develop an acute rejection or a chronic rejection which can evolve rapidly after transplantation. To define better physiopathology and chronic rejection therapies after transplantation is becoming essential.
TRANPLANTED patients is becoming an ageing population
The growing number of transplanted patients, being old and with final renal failure, leads toward an ageing population of transplanted patients. This ageing population is all the more facing infectious risks and cancers after transplantation. The fact of knowing before transplantation, the individual risk factors which may lead to post transplant complications would enable us to adapt quickly immunosuppressive therapies.
MAIN research investigations developped by the centaure network to fight against late graft loss
CENTAURE teams are working together, sharing their research laboratories discoveries and their tranplanted population of patients to fight against various factors involved in long-term graft loss.
Here are the main research aim:
- To fight against ischaemia reperfusion: we will take advantage of perfusion machines, preservative liquids for therapies of patients receiving kidney from non optimal donnors. The evaluation will be defined by randomized and multicenter studies
- Mechanisms and understanding chronic rejection: chronic rejection mechanisms will be studied thanks to biopsies from patient with immunological risks, thanks to the DIVAT data bank, animal models developped in immunological laboratories of the 3 CENTAURE centres. Innovative therapies will be studies regarding this patient population.
- Personalized medicine in post transplantation follow-up: use of DNA chips will enable us to detect with more precision patients presenting a high risk of graft loss and to propose an early and individualized therapy for every patient.
- Markers research for rejection or tolerance, and toxicity of immunosuppressive drugs, will allow the development of a personalized medicine adjusted to every patient and this will decrease complications after transplantation.
- New methods of quantification of interstitial fibrosis, key element in graft loss, and its development within CENTAURE teams, will allow to follow-up precisely and measure the efficiency of undertaken therapies.
- Recurrence of initial diseases on grafts will be studied with a special attention in the laboratory of the Nantes team.
