The induction of vascular renal allograft rejection by leukocyte sensitizatin.

Abstract

Abstract Human renal allograft rejection occurring within the first 2 months after surgery is frequently a vascular phenomenon, characterized by fibrinoid necrosis and endothelial cell proliferation of small vessels and plugging of glomerular capillaries with platelets and fibrin. This contrasts with interstitial edema and mononuclear cell infiltration, and only minimal vascular involvement, usually seen in renal allograft rejection in animals but also seen in man. To investigate this difference, 18 dogs were administered intravenous donor buffy coat prior to transplantation. These were compared to 7 dogs similarly treated except that buffy coat was not administered. Three autografts served as controls. All dogs received azathioprine daily (3 mg. per kilogram) beginning on the day of the operation. Daily assays of renal function, dog survival time, platelet counts, platelet survival times, and repeated biopsy specimens were compared. A marked difference between the immunized and nonimmunized groups was apparent morphologically. In the immunized group, vascular wall necrosis, platelet and fibrin plugging of glomerular capillaries, and endothelial cell proliferation were striking features of the rejection process. The over-all appearance was similar to that often seen in severe early (but not hyperacute) rejection in man. No significant difference in dog survival times or platelet studies was demonstrable between the groups. It is suggested that in man, the morphologic changes seen in early vascular rejection are a result of prior sensitization to transplantation antigen. Drug trials in animal transplantation aimed at studying reversal of the vascular aspects of rejection should be performed on animals exposed preoperatively to donor antigen.