Multiple new immunosuppressive drugs are becoming available for prevention of rejection in renal transplant recipients. Determining which of these agents provides the best immunosuppressive protocol will require large number of patients. An individual center will be unable to generate such information. Multi-center studies such as that proposed will provide evaluation of these agents at a much more rapid pace and will thus permit the rapid dissemination of this new technology. We propose that the cooperative trial initiate randomized study of FK506 versus cyclosporine in a sequential therapy protocol. Cadaver transplant recipients will receive prednisone and azathioprine at the time of surgery with antilymphocyte globulin (ALG) started on the first post operative day. Patients will be stratified for delayed graft function (DGF), diabetes, transplant number (primary or retransplant), and for retransplants whether the first graft was lost at < vs > 1 year, and will be randomized to receive either cyclosporine or FK506 beginning on the 5th post operative day. We will assess patient and graft survival, persistence of DGF, serum creatinines at 1 week, 2 week, 1 month and monthly thereafter, incidence of complications, drug side effects, infections, rejection episodes, and malignancies. We propose that evaluation of this agent be followed by evaluation of Rapamycin, Deoxyspergualin, Mizoribine, and Succinylacetone as either FK506/cyclosporine substitutes or as azathioprine substitutes. In addition, the new monoclonal antibodies could be utilized in a randomized arm versus ALG. However, each of these studies would compare a new agent or combination of agents against best known therapy.
