Six patients with terminal uremia due to glomerulonephritis or pyelonephritis were treated with heterografts from East African baboons. Immunosuppressive therapy was provided both before and after operation with azathioprine and prednisone and postoperatively local transplant irradiation and actinomycin C were administered intermittently. The individual rejection episodes in the post-transplant period could be reversed relatively easily but these reemred vigorously and repetitively, making it impossible to relax the stringent requirements of antirejectmion therapy. The continued need for high-dose immunosuppressive therapy precipitated lethal infections in the majority of cases.
The patients lived for 19 to 98 days after heterotransplantation. Four died with the baboon kidneys still in placc after 19, 23, 35, and 49 days. In the other two cases the heterografts were removed after 60 and 49 days respectively, at a time when urine excretion was still present, and homografts from volunteer convict donors were placed on the opposite side. Both the latter recipients died of septic complications following the second operation, after 39 and 44 days. Complete cessation of heterograft urine excrelion appeared only in two cases, although rend function was failing in the remainder prior to death or before removal of the heterografts. The relation of renal function to changes in heteroagglutinin and hemagglutinin titers is described.
After residence in the host for 19 to 60 days, all the heterotransplants were heavily infiltrated with plasma cells and large lymphoid cells with pyroninophilic cytoplasm. There was also disruption of peritubular capillaries, interstitial edema, widespread tubular damage, swelling of endothelial cells lining arterioles, fibrinoid necrosis of the walls of arterioles and interlobular arteries, and narrowing and obstruction of interlobular arteries by fibrin and platelet deposits on the intima. The pre-glomerular vascular lesions were accompanied by focal infarcts and extensive interstitial hemorrhages. All the pathologic changes were more severe than those seen by Reemtsma in a comparable series of chimpanzee-to-man heterotransplants, where cellular infiltration was slight and vascular lesions uncommon in the presence of major blood group incompatibility between donor and recipient.