IMPROVEMENT OF KIDNEY TRANSPLANT SURVIVAL AFTER GRAFT PRETREATMENT WITH CYCLOSPORIN A

Abstract

In an effort to improve kidney allograft survival after transplantation, cyclosporin A (Cy A) was used as a graft pretreatment under varying conditions. Initial studies established that 12.5 mg of Cy A per kidney was the ideal concentration for graft pretreatment. This study analyzed the role of temperature in the flushing solution with the drug, 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 and 4 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/day days, followed by 2.5 mg/kg/day until death or sacrifice). Animals transplanted with kidneys flushed at 25 and 4 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 C, 5 of 10 animals survived for more than 60 days, whereas Cy A at 4 C showed 3 of 10 animals living that length of time. It was evident that warmer temperatures (25 C) improved the prolonging effect of Cy A in the survival of pretreated kidney grafts. Based on our previous work and current findings, we felt that 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, it is possible that temperature may affect the reaction of Cy A with the allograft's cell membrane and in this way prolong allograft survival. Further studies both in vivo and in vitro will help to answer these questions and lead us to potential clinical applications of Cy A graft pretreatment.