KIDNEY-TRANSPLANT IMMUNOSUPPRESSANTS OF TODAY .2. TRANSPLANT IMMUNOSUPPRESSIVE AGENTS

Renal transplantation is the treatment of choice for end-stage renal f ailure. it allows full rehabilitation and return to a state of normal physiology. Long-term renal transplant results are far from perfect an d the demand for organs exceeds the available supply. With a half-life of 7-8 years, most grafts will progressively fail due to chronic reje ction which is difficult to treat with the available immunosuppressive agents. Various clinical risk factors, including early acute rejectio n, ongoing silent rejection and drug toxicities, all predispose to a m ore rapid rate of chronic graft loss which is the major stumbling bloc k for the longterm success rate. This review identifies and evaluates the current and newer immunosuppressive agents developed for managemen t of clinical renal transplant recipients. It also discusses further e xploration of the new frontiers of immunosuppressive therapy developed in the field of transplantation. Dual induction and maintenance azath ioprine and corticosteroids were used until late 1979 to allow cadaver ic allograft transplantation. This combination is unsatisfactory becau se of a rejection rate of more than 60%. Therefore, this regimen is cu rrently ill-advised. The advent of ciclosporin A in 1978 and the use o f polyclonal and monoclonal antibodies have improved the short-term gr aft survival rates and decreased the incidence of refractory acute rej ection. Triple drug immunosuppression with prednisone/azathioprine/cic losporin is used by more than 50% of transplant centers for induction. The incidence of acute rejection with this regimen is in the range of 45%. Almost 90% of these rejection episodes are amenable to treatment with high-dose intravenous steroids and/or polyclonal or monoclonal a ntibodies. The addition of polyclonal or monoclonal antibodies to the triple regimen therapy is associated with a decreased number and sever ity of early acute rejections. The impact of bioreagents on the long-t erm renal allograft success rate is, however, controversial. A triple immunosuppressive regimen with ciclosporin/steroids/mycophenolate or r apamycin has a superior effect in reducing the incidence of acute reje ction to 15-25%. The long-term benefit of mycophenolate or rapamycin r emains to be seen. The newer bioreagents are expected to play a permis sive role to prevent acute rejection and improve long-term graft funct ion.