Prevention and treatment of renal allograft rejection: New therapeutic approaches and new insights into established therapies

Renal transplantation is the preferred treatment modality for patients with ESRD who are good surgical risks and able to comply with chronic immunosuppressive medications. Clinical transplantation has advanced significantly, with most transplant centers reporting 1-yr renal allograft survival rates of better than 80%. Nevertheless, rejection and a progressive loss of allografts over time continue to occur. The immunosuppressive agents currently used may lead to the development of life-threatening infections, malignancies, and advanced atherosclerosis as a consequence of some of their side effects. This review examines the mechanisms involved in allograft rejection as currently understood. The recent knowledge into the mechanism of action of cyclosporine, FK506, and rapamycin on T cell activation is presented. Information recently available on some of the established therapies such as steroids, antimetabolites and monoclonal antibodies as well as the newer agents is also discussed. The interaction between clinical transplantation and basic research in immunology continues to result in exciting advances in both fields.