The use of cyclosporin A in clinical organ grafting.
Experiments in animals with organ allografts showed that Cyclosporin A (CyA) was an extremely powerful immunosuppressant with a good therapeutic index. A pilot study of the drug in human recipients of renal allografts revealed an unexpected side effect, nephrotoxicity, which made care of patients difficult. Following a policy of deliberate hydration of patients in the perioperative phase and withholding CyA until diuresis was occurring in the graft, excellent results have been obtained in clinical practice. An 82% actuarial functional survival at both one and two years has been obtained in the 59 patients treated with this protocol. A multicenter trial is now in progress in eight centers in Europe, comparing CyA used in the manner described above with conventional azathioprine and steroids. CyA has also been used in 17 recipients of liver allografts, ten of whom are still alive and 11 recipients of segmental pancreatic allografts, one of whom remains off insulin after two and a quarter years. Sudden graft failure occurred between three months and two years in three patients whose pancreatic duct had been occluded. The authors' most recent segmental pancreas graft has been drained into a long roux loop without complications. The main objective in the use of this drug is to obtain consistent immunosuppression without nephrotoxicity. It is possible that maintaining blood level between defined limits would improve results.