Low toxicity immunosuppressive protocols in renal transplantation

With the development of increasingly potent new immunosuppressive agents, the outcomes after renal transplantation have continued to improve. However, patients continue to require long term chronic immunosuppression. The toxicities associated with cyclosporine, azathioprine, prednisone, and anti-lymphocyte antibodies are well known; those associated with the newer agents, tacrolimus, mycophenolate mofetil, and sirolimus, have also been described. In an attempt to minimize these side effects, a number of low toxicity protocols have been developed. They can be categorized into those that withdraw, minimize, or avoid calcineurin inhibitors, those that withdraw or avoid steroids, and those that withdraw adjunctive (third) agents. This presentation will review the various low toxicity protocols that have been utilized in clinical renal transplantation. While there are a number of combinations that have been tried, it is not yet clear which regimen(s) will prove to be the most efficacious and least toxic. In addition, the presentation will also describe preliminary outcomes with a new tolerogenic protocol developed at the University of Pittsburgh. This regimen combines steroid avoidance with low doses and gradual tapering of calcineurin inhibitors, and has shown considerable promise in kidney, pancreas, liver, and intestine recipients.