Present and future of immunosuppressive therapy in kidney transplantation

Patient and graft survivals following kidney transplantation, the treatment of choice for patients with end-stage renal disease, have dramatically increased in recent years. This is mainly due to improvements in immunosuppression and medical care posttransplantation. Original immunosuppressive protocols were based on glucocorticoids and azathioprine but many patients developed acute rejection requiring high-dose prednisone. These immunosuppressive protocols nonselectively inhibit elements of host resistance, such as monocytes, granulocytes, and macrophages, and because of this high mortality rates due to opportunistic infections were often observed. The introduction of newer agents, such as tacrolimus, sirolimus, anti-interleukin-2 receptor monoclonal antibodies, and mycophenolate salts with a more selective mechanism for T- and B-cell alloimmune responses, led to a reduction in the incidence of infection. Clinical trials based on the combination of these drugs with steroids and cyclosporine show a reduced incidence of acute rejection episodes (<10%) and allow a steroid-sparing policy in kidney transplantation. Today, the main problem is related to the adverse events associated with vigorous and prolonged immunosuppression, mainly cardiovascular disease, infections, and malignancies. Further studies are required to find the optimal dosage and combination of new and old drugs in renal transplantation. It is likely that calcineurin inhibitors (CNIs) will continue to be prescribed in the near future, but their association with synergistic drugs will allow using them at minimal doses.