PREDICTIVE FACTORS FOR CHRONIC REJECTION

Of the 4 types of graft rejection (immediate or delayed hyperacute, ac ute and chronic), acute rejection may be a forerunner of chronic rejec tion, either because acute rejection is evidence of the intensity of t he host immune response or the inadequacy of immunosuppressive treatme nt, or because each episode of acute rejection may lead to irreversibl e tissue damage. True chronic rejection is the result of a complex pro cess determined by factors such as the intensity of the host immune re sponse against donor antigens and the nature and intensity of the immu nosuppressive treatment. Histologically, it shows a triad of vascular damage, interstitial fibrosis and inflammatory infiltrates. However, t he first 2 of these changes are not specific for chronic rejection, an d may also be caused by chronic graft destruction (CGD), which results from a variety of deleterious pathological processes, amongst which t he 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 rej ection pre-existing graft damage caused by donor factors such as hyper tension, atherosclerosis and aging the existence, and in particular th e severity, of postoperative acute renal insufficiency, which is linke d to the condition of the donor before organ removal, the duration and quality of storage of the organ, and to secondary lesions occurring d uring reperfusion recipient factors such as hypertension, diabetes, ob esity, heart failure and tobacco use infections, particularly by cytom egalovirus use of drugs toxic to the graft depletion of nephrons. Alth ough more invasive than clinical methods, serial histopathology on bio psy samples from a number of sites remains the best method for predict ion 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. Ho wever, we should still attempt to predict the occurrence of chronic re jection and try to prevent it by paying particular attention to the le vel of, and compliance with, maintenance immunosuppression. In paralle l, it is important to remember that even in the absence of an immune r esponse against the graft it may be damaged by a number of pathologica l processes. Prevention of these non-immunological processes will be o f particular importance in the future when induction of specific toler ance to the graft can be achieved.