Optimization of the use of cyclosporine in renal transplantation

Abstract

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant performed by Hume et al in 1952, there has been an elusive search for agents rendering the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ while sparing nonspecific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes; chemical (pharmaceutical), biological (immunological), physical (radiological), and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, azathioprine, cyclosporine (CsA), tacrolimus, mycophenolate mofetils and so on made an epoch at each stage in history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and /or B cells by inhibiting cytokine synthesis (CsA, FK506), cytokine action (Rapamycin), or cell differentiation (15-deoxyspergualin) pathways rather than to act on immune systems in a nonselective fashion. CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving the patient and graft survival. Sandimmun Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are under way to determine its effectiveness and safety. Therapeutic drug monitoring and combination therapy with CsA are investigated also.