Current and Future Immunosuppressive Strategies in Renal Transplantation

Karen L. Hardinger, Pharm.D.; Matthew J. Koch, M.D.; Daniel C. Brennan, M.D., FACP


Pharmacotherapy. 2004;24(9) 

In This Article

Abstract and Introduction

The past decade has witnessed the introduction of several new immunosuppressive agents. The availability of these new pharmacologic offerings has not diminished the challenge of achieving a balance of adequate graft protection while minimizing the consequences of excessive immuno-suppression. For renal transplant recipients, maintenance immuno-suppression generally consists of a calcineurin inhibitor in combination with an antiproliferative agent and a corticosteroid; more recently, mammalian target of rapamycin inhibitors have been used. Excellent results have been achieved at many transplant centers with combinations of these agents in a variety of protocols. Regimens designed to limit or eliminate calcineurin inhibitor and/or corticosteroid therapy are actively being pursued in the transplant community. Allograft tolerance and xenotransplantation are being studied, and the knowledge gained from the effort may help in the development of innovative strategies and new immunosuppressive agents.

Advances in immunosuppressive strategies over the past 2 decades have led to significant improvements in the field of renal transplantation. The availability of cyclosporine in the 1980s revolutionized the practice by lowering acute rejection rates and improving short-term allograft survival. New therapeutic protocols for older agents and newly introduced agents in the 1990s further reduced the rate of acute rejection. Despite these advances, clear evidence of a beneficial effect on long-term allograft survival is lacking. Furthermore, these agents are plagued by adverse effects of chronic immunosuppressive therapy, which range from cosmetic effects to those that threaten allograft function or patient survival.

The available immunosuppressive agents can be classified into five categories: immunophilin-binding agents (cyclosporine, tacrolimus), mammalian target of rapamycin (mTOR) inhibitors (sirolimus, everolimus), antiproliferative agents (azathioprine, mycophenolate mofetil [MMF]), antibodies (antilymphocyte and antithymocyte globulins, basiliximab, daclizumab), and corticosteroids. Knowledge gained from new trials of these agents may allow them to be administered in a manner that limits toxicity and prolongs functional life of the graft. Some of these advances may move us closer to the ultimate goal of allograft tolerance, realizing the panacea of immunologic acceptance of the allograft in the absence of chronic immuno-suppression while maintaining immunologic response to other third-party antigens.