Facteurs prédictifs du rejet chronique

Summary

Of the 4 types of graft rejection (immediate or delayed hyperacute, acute and chronic), acute rejection may be a forerunner of chronic rejection, either because acute rejection is evidence of the intensity of the host immune response or the inadequacy of immunosuppressive treatment, or because each episode of acute rejection may lead to irreversible tissue damage. True chronic rejection is the result of a complex process determined by factors such as the intensity of the host immune response against donor antigens and the nature and intensity of the immunosuppressive treatment. Histologically, it shows a triad of vascular damage, interstitial fibrosis and inflammatory infiltrates. However, the first 2 of these changes are not specific for chronic rejection, and may also be caused by chronic graft destruction (CGD), which results from a variety of deleterious pathological processes, amongst which the importance of true chronic rejection is impossible to measure.

The development of CGD correlates well with a number of factors, including:

• the number and, in particular, the severity of episodes of acute rejection

• pre-existing graft damage caused by donor factors such as hypertension, atherosclerosis and aging

• the existence, and in particular the severity, of postoperative acute renal insufficiency, which is linked to the condition of the donor before organ removal, the duration and quality of storage of the organ, and to secondary lesions occurring during reperfusion

• recipient factors such as hypertension, diabetes, obesity, heart failure and tobacco use

• infections, particularly by cytomegalovirus

• use of drugs toxic to the graft

• depletion of nephrons.

Although more invasive than clinical methods, serial histopathology on biopsy samples from a number of sites remains the best method for prediction and monitoring of CGD. Vascular echography of the arteries of the transplant may give useful information in the future.

The association of true chronic rejection with a number of pathological processes that have no relation to the immune response makes diagnosis difficult. However, we should still attempt to predict the occurrence of chronic rejection and try to prevent it by paying particular attention to the level of, and compliance with, maintenance immunosuppression. In parallel, it is important to remember that even in the absence of an immune response against the graft it may be damaged by a number of pathological processes. Prevention of these nonimmunological processes will be of particular importance in the future when induction of specific tolerance to the graft can be achieved.