Graft pretreatment with cyclosporin A. Long-term study including four trials in one and a half years

Four trials were conducted to establish whether Cyclosporin A (Cy A) could be used as a graft pretreatment to prolong the graft function and animal survival of kidneys transplanted into bilaterally nephrectomized mongrel dogs. The first nonrandomized trial analyzed various parameters such as concentration, flush temperatures, effect of reflushing, and the need for subsequent minimal immunosuppression. By analyzing data from the ten groups in this trial, we established that 50 mg/l Cy A could be flushed successfully at either 4 C or 25 C without nephrotoxic effects. This concentration was found to prolong graft function and animal survival in some animals greater than 100 days. Reflushing the kidney after primary graft pretreatment with Cy A did not entirely remove the immunosuppressive effect of the drug as significant prolongation of survival also was observed in this group. In addition, minimal immunosuppression with azathioprine was necessary to observe a delay in the onset of rejection and prolongation of animal survival when Cy A was used for graft pretreatment. Trials 2 and 4 compared the efficacy of the original batch that was obtained later. The effects observed in Trial 1 and reproduced in Trial 3, which were randomized and double blinded using the original batch, were not seen in either Trials 2 or 4. This may have been related to the amount of time that the Cy A was dissolved in ethanol prior to its use or the batch of Cy A utilized. These preliminary results indicate that Cy A, when used for graft pretreatment under certain conditions, can delay the onset of rejection and prolong animal survival of transplanted renal allograft recipients.