Immunosuppression for long-term maintenance of renal allograft function.

The incidence and severity of acute rejection episodes was markedly reduced by the introduction of new immunosuppressive drug regimens for renal transplantation, resulting in improved graft survival at 1 year. However, only modest improvement has been shown in long-term graft function rates. This overview evaluates the efficacy of currently used immunosuppressive drugs and drug combinations for long-term maintenance therapy. Prospective controlled trials rarely extend beyond 5 years; therefore, registry data and retrospective reports have also been employed. From currently available data it may be concluded that the initial beneficial effect of ciclosporin (cyclosporin) is lost 10 years after transplantation. Tacrolimus is an alternative to ciclosporin with a different profile of adverse effects and a higher efficacy in acute rejection treatment. For long-term maintenance, projected half-lives of kidney graft function are in favour of tacrolimus. Mycophenolate mofetil (MMF) has been shown to significantly reduce the incidence of early rejections. However, the improved long-term graft survival reported in retrospective studies has still to be confirmed in controlled trials. There is no convincing evidence for superiority of triple therapy including prednisone (or prednisolone), calcineurin inhibitors and azathioprine/MMF over dual therapy without azathioprine/MMF with respect to long-term outcome. Withdrawal of corticosteroids or calcineurin inhibitors clearly reduces adverse drug effects but carries the risk of acute rejection episodes. Avoidance of corticosteroids by using new immunosuppressive drug combinations may be an option to minimise toxic adverse effects in the future. At present, it seems unjustified to convert renal transplant recipients with stable graft function and tolerable adverse effects from one drug to another solely in expectation of future benefits. Acute early or late rejection episodes and intolerable adverse effects are good reasons for conversions between calcineurin inhibitors or cytotoxic agents. Chronic allograft nephropathy with slowly deteriorating graft function remains an unresolved problem.