Renal transplantation: basic concepts and evolution of therapy.

Abstract

Within the last 5 years, dramatic changes in the area of renal transplantation have occurred. There have been shifts in the dominant types of rejection, and in the types and utilization of immunosuppressants. Hyperacute rejection is now rarely seen, and acute cellular rejection within the first 6 to 12 months has been reduced to about 10%. However, humoral/antibody-mediated rejection has become a more prevalent problem. In the area of immunosuppressants, the ability to reduce acute cellular rejection to about 10% has been achieved through more judicious use of calcineurin inhibitors (cyclosporine and tacrolimus), increased use of mycophenolate mofetil, and the recent introduction of sirolimus (rapamycin). The polyclonal antibody (antithymocyte globulin), as well as monoclonal antibodies directed against the alpha chain of CD25 (daclizumab and basilixamab), have added substantially to the improved success of renal allografts. Because of numerous serious toxicities from glucocorticoids and calcineurin inhibitors, particularly cyclosporine, new studies are utilizing calcineurin-free and/or glucocorticoid avoidance or rapid elimination protocols often in combination with a monoclonal antibody and sirolimus. New immunosuppressants such as FTY720 and Campath-1 are also under study. In addition to its use in treating patients with low-level donor-specific antibody before transplantation in order to avoid hyperacute rejection, apheresis is utilized in various combination protocols after transplantation in the management of humoral/antibody-mediated rejection, in the treatment of hemolytic uremia syndrome that sometimes occurs with calcineurin inhibitors and sirolimus, as well as in the treatment of focal segmental glomerulosclerosis that has a major risk of recurrence in renal transplants.