Scientific Rationale
The high rate of chronic allograft failure obviously has a very serious socio-economic impact for transplant patients and their families. This can also spill over to affect clinical transplant programmes and patients awaiting organ transplantation, with up to 30% of patients on the kidney transplant waiting list having already rejected one or more transplanted kidneys. The ever increasing number of patients on transplant waiting lists has put a greater emphasis on the preservation of organ function and increased use of donor organs which would previously have been considered too compromised for clinical use.
Organ transplantation is often the only treatment option for patients with end stage organ failure. Despite its success the number of available organs has remained relatively constant while the numbers on waiting lists have grown. At present over 15,499 patients are on active organ waiting lists in the Eurotransplant zone, which contains 124.6 million inhabitants (http://www.eurotransplant.org/cms/). As a consequence of better immunosuppressive drugs transplant loss due to acute rejection is now rare. More than 80% of heart, lung, kidney and liver allograft survive for more than one year. However, most of these transplanted organs undergo a process of chronic rejection which, in the UK, results in the failure of 35% of transplanted kidneys, 40% of hearts and livers and more than 70% of lungs within 10 years.
Several factors, including alloimmunity, recurrent disease and drug toxicity contribute to this chronic allograft failure. Irrespective of the cause, common pathological features include the loss of functional tissues such as airway, renal or biliary epithelium, or cardiac vascular endothelium with replacement by fibroblasts and ECM. Although T cell-mediated acute rejection is a commonly identified risk factor for subsequent chronic allograft failure, reductions in the rate of acute rejection brought about by modern immunosuppressive drugs have not translated to significantly reduced rates of chronic allograft failure. The work of this partnership wishes to address opportunities to prolong organ survival after transplantation.
