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

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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.

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