CYCLOSPORINE (SANDIMMUN(R)) IN CADAVERIC RENAL-TRANSPLANTATION - 10-YEAR FOLLOW-UP OF A MULTICENTER TRIAL

Cyclosporine (CsA) was first used clinically as an immunosuppressant in organ transplantation 16 years ago (1). While this initial study demonstrated the potent immunosuppressive properties of the drug, it also identified, for the first time, the nephrotoxic side effect which has influenced the subsequent development of protocols for the use of this agent. As a result of this initial pilot study, a prospective randomized multicenter trial of CsA monotherapy against azathioprine and steroids was undertaken by 8 transplant centers located throughout Europe. The results from this trial demonstrated the superiority of CsA immunosuppression over the ''conventional'' arm (2). With the passage of time, many different CsA protocols, combining CsA with a variety of other immunosuppressants, have been developed and the immunosuppressive value of CsA in organ transplantation has been confirmed repeatedly by many centers. The major concern now is how best to deploy CsA so as to limit its nephrotoxicity while retaining its immunosuppressive potency. Debate also surrounds the use of CsA monotherapy compared with combination protocols. In particular, the immunosuppressive value of long-term adjunctive steroid treatment and whether this is worth the penalty of the steroid side effects await clarification. The issue now to be addressed, therefore, is how best to treat transplant recipients with a view to obtaining very long-term graft survival with minimal morbidity. Thus, those patients selected for that original European multicenter trial become a valuable source of information on the long-term effects of CsA therapy. In particular, it allows one to question whether the nephrotoxic effects of CsA lead to an unacceptable level of toxic damage to the renal transplant. In addition, the possibility that the immunosuppressive power of the drug may result in a high incidence of tumor development can also be investigated in this patient population. The 8 centers involved in the trial have continued to follow the progress of the patients selected for both arms of the study. This article describes the result of a 10-year follow-up analysis.