Prophylaxis of renal transplant rejection with new chemical immunosuppressants (tacrolimus, mycophenolate mofetil, sirolimus): will these drugs make antibody induction superfluous?

The balance between counteracting acute rejection and drug-related side effects remains a major clinical issue despite the introduction of effective modern chemical immunosuppressive drugs, such as tacrolimus, mycophenolate mofetil, and sirolimus. Tacrolimus is used as a primary drug, whereas mycophenolate mofetil works best as an adjunctive drug to either cyclosporine or tacrolimus, and the role of sirolimus as a primary or secondary drug has yet to be fully determined. All three agents have in several studies demonstrated their ability to reduce the incidence of acute rejection, but none has improved the survival rates. Importantly, the new chemical immunosuppressants are associated with significant drug-specific side effects. These side effects are dose related and they are therefore most often observed during the early postoperative period when patients are given high doses of immunosuppression. Future protocols, combining new genetically modified biologic agents and chemical immunosuppressants, may permit the use of lower doses of the latter, resulting in fewer side effects while still maintaining a low incidence of rejection. In addition, the use of biologic reactants may help to induce transplantation tolerance by targeting individual molecules by interefering with specific signals that are sent to immunocompetent cells. We conclude that chemical immunosuppressants such as tacrolimus, mycophenolate mofetil, and sirolimus do not eliminate the need for antibody induction by biologic reagents in the prophylaxis of renal transplant rejection.