Transplantation of a paired organ, the kidney.

Abstract

Transplantation of the kidney, at least between related donor-recipient pairs, is now a clinically feasible procedure. A recent analysis of more than 2000 human renal allografts reported to the Transplantation Registry indicated that the two-year survival rate for sibling donor-recipient pairs is approximately 80 per cent. The results of recent transplantations of cadaver kidneys shows a success rate comparable to that of open heart surgery for acquired valvular disease. I believe, therefore, that if a living, related donor is available, the results justify the transplantation of a kidney at an earlier stage than previously. Peripheral neuropathy and other irreversible consequences of advanced renal failure may thus be avoided. A number of immunological problems, however, still exist. The agents now available for immunosuppressive therapy (azathioprine, prednisone, and antilymphocyte globulin therapy) are tools not sharp enough for the job. At present there is no evidence that antilymphocyte globulin has significantly improved the results of kidney transplantation in humans, although it is unquestionably a potent immunosuppressive agent in the experimental animal. Moreover, these agents cause serious side effects: infection, failure of wound healing, enhancement of the growth of malignant tumors which have been inadvertently transplanted, and an increase in the incidence of malignant tumors of the lymphatic system. This latter complication was most dramatically pointed up by a recent communication from the Cleveland Clinic noting the appearance of a reticulum cell sarcoma at the site of injection of antilymphocyte globulin. Delayed damage to the renal allograft may also present serious problems. After a patient has apparently done well for a period of two or three years, the transplanted kidney may develop lesions of glomerular nephritis. In some cases this appears to be due to the development of the same disease that had destroyed the original kidneys of the recipient, while in other cases the lesions must be attributed to the rejection process. A dramatic illustration of the latter was a patient who developed typical lobular glomerulonephritis in a renal transplant without any history of renal disease. Allografting was necessitated in his case by the mistaken removal of a single ectopic kidney. Similar lesions also occur in the transplanted kidneys of normal rats. Enlargement and proliferation of endothelial and mesangial cells can be seen three to five days after transplantation. Glomerular capillaries are partially occluded at this time, and granular deposits of IgG and beta 1 C globulin on capillary walls and mesangial areas can be demonstrated by immunofluorescence. Deposits on the epithelial side of the basement membrane can be demonstrated by electronmicroscopy. Another type of lesion, also related to rejection, may occur in kidney transplants that have functioned well for long periods. Obliterative vascular disease may develop without glomerular lesions. Again, a study of the sequential events in the rat kidney may help explain this result. Numerous mononuclear cells