IMPROVEMENT OF KIDNEY TRANSPLANT SURVIVAL AFTER GRAFT PRETREATMENT WITH CYCLOSPORIN A

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Abstract
To improve kidney allograft survival after transplantation, cyclosporin A (Cy A) is used as a graft pretreatment under varying conditions. It was established that 12.5 mg of Cy A per kidney was the ideal concentration for graft pretreatment. The role of temperature in the flushing solution with the drug was analyzed to determine whether this parameter would have a significant effect on allograft survival. Unrelated mongrel dogs were used as donors and recipients for all studies. Control kidneys (group 1 (n = 8) and group 2 (n = 8)) were flushed with heparinized Ringer''s lactate (250 ml) at 25.degree. and 4.degree. C, respectively. Kidneys in groups 3 (n = 10) and 4 (n = 10) were graft pretreated at 25 and 4 C by flushing the kidneys with Cy A (12.5 mg) in 250 ml of Ringer''s lactate prior to allografting. All donor kidney allografts were transplanted into the right iliac fossa of bilaterally nephrectomized recipients. Minimal immunosuppression consisted only of azathioprine (5 mg/kg per day .times. days, followed by 2.5 mg/kg per day until death or sacrifice). Animals transplanted with kidneys flushed at 25.degree. and 4.degree. C survived for all 11.6 .+-. 0.8 (mean .+-. SD) and 16.5 .+-. 3.96 (mean .+-. SD) days, respectively. Only the addition of Cy A improved the survival of minimally immunosuppressed recipients. When Cy A was used at 25.degree. C, 5 of 10 animals survived for more than 60 days, whereas Cy A at 4.degree. C showed 3 of 10 animals living that length of time. Warmer temperatures (25.degree. C) improved the prolonging effect of Cy A in the survival of pretreated kidney grafts. Graft pretreatment with Cy A could significantly prolong kidney allograft survival. Although the exact mechanism for the action of Cy A during graft pretreatment is not known, temperature may affect the reaction of Cy A with the allograft''s cell membrane and in this way prolong allograft survival.

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