Xenogeneic renal preservation for transplantation in primates. I. Transient acute rejection response in autografts.

Abstract

SUMMARY A nonhuman primate model for xenogeneic renal preservation has been described which overcomes a number of immune phenomena previously felt to complicate this method. Macaque kidneys stored for 5 days in immunosuppressed baboons and reimplanted into the original donor evoked responses with elements of both hyperacute and first-set rejection. Although complement depletion and cellular invasion were shown to play a role in the attempted graft rejection, they were noted to be self-limited and spontaneously reversible. A moderate periglomerular, periarteriolar mononuclear cell invasion occurred within 24 hr of reimplantation. This invasion reached a peak at 7-10 days, when already accompanied by the appearance of focal and diffuse glomerular basement membrane thickening, to which were added hypertrophy of the parietal epithelium of Bowman's capsule and increased numbers of mesangial cells. At 14 days, the infiltrate began to wane, and it gradually disappeared by 28 days. The glomerular changes also disappeared, but elements were still present after 4 months. At 6 months, parenchymal architecture was normal. Dramatic depressions in peripheral lymphocyte and C3 levels accompanied the changes during the 24 hr postreimplantation. Although the total lymphocyte count returned to normal after 7 days, 4 months were required for a reversion of peripheral complement levels. All kidneys eventually went on to function for prolonged periods without evidence of physiological or histological change. These results have established the feasibility and potential value of in vivo xenogeneic storage.