CTLA4 IG ON RENAL ALLOGRAFT SURVIVAL: TREATMENT DELAY & COMB W/ CYCLOSPORINE

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The aim of this study was to test the hypothesis that CTLA4-Ig will prolong survival of renal allografts in a nonhuman primate model. CTLA4-Ig has been shown to modify the allograft rejection response to produce prolonged graft survival and/or induce specific unresponsiveness in rodent models. Adult rhesus macaques (11.8-13.5 kg) were utilized for these studies. Ten animals received an allogeneic renal transplant, a left nephrectomy and simultaneous right contralateral ureter ligation. The paired transplants were performed simultaneously by exchange of kidneys between recipient individuals. One recipient in each pair was treated with CTLA4-Ig and the other served as a control being treated with human albumin. Renal allografts in the control treatment group promptly fail (4-8 days) and the histologic analysis suggests both a cellular and humoral immune mediated mechanism. CTLA4-Ig treatment in one of four recipients was associated with marked prolongation of allograft su rvival. One CTLA4-Ig treated recipient died secondary to necrosis of the distal transplant ureter and was not included in the analysis. In summary, the results of this pilot study suggest that CTLA4-Ig has the ability to prolong primate renal allograft survival.