THE EFFECT OF HIGH DOSE STEROID AND CYCLOPHOSPHAMEDE ON PERFUSED CANINE RENAL HOMOGRAFTS

Abstract

This study initially was undertaken to assess the effect of various combinations and dosages of known lymphocytotoxic drugs [methylprednisolone (MP) and cyclophosphamide (Cy)] on subsequent survival of machine-perfused canine renal homografts. Group 1 served as the control, with kidneys being perfused for 5 h in the standard manner and then transplanted. Group 2 animals received kidneys that were perfused with the standard perfusate containing 2 g of MP and 1.5 g of CY. Group 3 perfusate contained 2 g of MP, and group 4 perfusate contained 1 g of MP and 1.5 g of CY. Control kidneys functioned an average of 7.8 days, which was similar to those in group 4, which functioned an average of 5.8 days. In groups 2 and 3, where 2 g of MP were added to the perfusate, the average survival was only 3.6 and 3.0 days, respectively. Needle biopsies of those organs exposed to 2 g of MP in the perfusate taken immediately after revascularization showed obliterated glomerular capillary loops, neutrophils in the glomerulus and, at 15 h, interstitial hemorrhage. Glomerular capillaries in control kidneys remained patent up to 7 days and interstitial hemorrhage was absent. These data indicate a dose-related injury by MP to the microvasculature of the kidney, especially the glomerular and postglomerular capillaries.