Experience with cyclosporine.

Cyclosporine ended the azathioprine-prednisone era of transplantation. For years prior to cyclosporine, regimens in transplant centers were relatively fixed and all patients received the same two drugs in nearly the same doses with adjustments made primarily for toxicities. Transplant physicians became expert in the side effects of steroids and azathioprine. Cyclosporine changed everything. Change is never easy, however, and initial resistance to changing protocols (especially for a new nephrotoxic drug) was only overcome by randomized, controlled trials. Cyclosporine increased allograft and patient survival rates without increasing opportunistic infections. However, as important were the changes in thinking that came about. It can be argued that cyclosporine contributed to expanding multicenter controlled trials in the transplant community. It also helped bring about concepts such as tailoring drugs to individual patients, drug minimization or elimination, use of polypharmacy, and focus on the first few weeks after transplant. Understanding of T-cell function and causes of renal dysfunction were brought into clearer focus by this exciting new agent.