Use of cyclosporine in renal transplantation

The first cyclosporine trials in renal transplantation began in Cambridge in 1978. Between 1982 and 1985 several large multicenter trials and the reports from large series of patients evidenced that cyclosporine was a major advance in the prevention of acute rejection episodes and in improving short-term and long-term graft survival. Cyclosporine also showed the capacity to mitigate immunologic risk factors, HLA mismatching, and lack of pretransplant transfusions. However, cyclosporine has the serious defect of being nephrotoxic. Induction therapy with OKT3, polyclonal antibodies, and more recently with anti IL-2R monoclonal antibodies allowed the delay of introduction cyclosporine in patients showing posttransplant graft dysfunction. Other relatively unsuccessful attempts for overcoming cyclosporine nephrotoxicity were made before the association of new xenobiotics such as mycophenolate mofetil or sirolimus permitted cyclosporine doses to be reduced. These combinations reduce acute rejection incidence to below 20%, with its consequent positive impact on long-term graft outcome and also allow a safer steroid sparing and withdrawal early posttransplantation. Also, the association of cyclosporine with other new compounds such as the lymphocyte homing FTY20 or the peripheral lymphocyte-depleting Campath-1-IgG is currently under clinical investigation. Cyclosporine's future place is yet to be established in the new era of immunosuppression.