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The State of British Medicine –7: Organ Transplantation

Organ transplantation has come of age and this would seem to be an appropriate time to look at what has been achieved. I will also try to point out some of the disappointments to those engaged in this work and hazard predictions for the future. At the beginning of this century Alexis Carrel worked out a technique of kidney grafting based on his methods of vascular suturing. In the early 1950s technical success with experimental kidney grafts could be expected, but it was clear that this was not enough to ensure satisfactory function of a transplanted organ. As with skin grafts, so with vascularized organ transplants: after an initial period of temporary 'take', changes occurred in the recipient which led to rapid and inexorable destruction of the graft. A second graft from the same donor was destroyed more quickly than the first. so the phenomenon fitted into the requirements of an immune reaction. Murray et al. (1958), at the Peter Bent Brigham Hospital in Boston, were able to avoid this biological hazard in the first successful clinical organ graft by transplanting a kidney, where no immune reaction could occur, namely where the donor and recipient were identical twins. Some of their earliest patients are now alive, the longest survivor having continuing good kidney function twenty-one years after operation. Two developments in the 1950s led to more widespread therapeutic kidney grafting. First, Scribner et al. (1960) in Seattle applied the principle of recurrent dialysis using an indwelling cannulation prosthesis for vascular access, to maintain patients without renal function in reasonable health. Secondly, effective immunosuppressive drugs became available in experimental animals with organ grafts, namely the use of steroids coupled with the thiopurine antimetabolite, azathioprine (lmuran), a close chemical relative of 6-mercaptopurine. Thus it became possible for desperately ill patients suffering from uraemia to be restored to health and maintained fit for surgery whilst the kidney transplant operation was planned and performed. Both immunosuppressive agents mentioned are sometimes totally ineffective when given at the maximum tolerated dosage. Nevertheless, more than 25 000 kidneys have now been transplanted in patients who have been treated primarily using azathioprine and steroids and the results have been encouraging enough for the procedure to be accepted as established rather than experimental therapy. Results between close relatives are particularly good. Kidney transplantation has been one of the most comprehensively documented new forms of treatment. A registry was set up initially in Boston and it then moved to Chicago. Follow up has been remarkably thorough from all over the world. With grafts between identical twins, where the organ from a living volunteer donor is likely to be in perfect condition when transplanted, 86% of the grafts were functioning at two years. The percentage of functioning grafts in the other donor categories are shown in Table 1. The longest functioning transplant coming from a blood relative who was not an identical twin is eighteen years, and the longest survival with a kidney from an unrelated cadaver donor is fourteen years. A kidney from a cadaver donor, in addition to having increased sensitivity to