Immunosuppressive treatment for kidney transplantation

Immunosuppressive treatment minimizes unwanted immune reactivity, but it also leads to complications such as metabolic disorders, cardiovascular diseases and malignant tumours. In this paper we summarise the recent developments in action mechanisms of available immunosuppressive drugs and their usage for renal transplantation. These drugs act at various levels of lymphocytic activation and proliferation, and they may have additive or synergic effects when combined. In the majority of patients, the immunosuppressive protocol includes a calcineurin inhibitor (tacrolimus or cyclosporin), an antimetabolite (mycophenolate mofetil or mycophenolic acid) and a corticosteroid. Most patients also receive induction with monoclonal or polyclonal antilymphocytic antibodies. These immunosuppressive drugs allow a one-year survival of renal allografts in over 90% of cases and an incidence of acute rejection episodes below 15%. In most cases, acute cell-mediated rejection can be reversed with pulse doses of methylprednisolone; less often antilymphocytic antibodies must be applied. Acute humoral rejection can be suppressed with high doses of intravenous immunoglobulines or low doses of cytomegalovirus hyperimmune globuline, in combination with plasmapheresis, to obtain a satisfactory reduction of anti-donor antibodies. This treatment also allows renal transplantation for sensitised recipients, or transplantation against a positive cross match or AB0 incompatibility. Less often, immunoadsorption, alemtuzumab, rituximab or splenectomy are applied. New immunosuppressive drugs and protocols are currently under investigation. Immunosuppressive agents and methods targeting the induction of immune tolerance to the donor organ are especially promising.