EFFECT OF CYCLOSPORIN A UPON SECOND-SET REJECTION OF RAT RENAL ALLOGRAFTS

Abstract

With the use of a DA to LEW rat renal allograft model, the ability of cyclosporin A to influence a second-set rejection was investigated. Sensitization of LEW rats was accomplished by performing DA to LEW skin grafts 4 to 5 weeks before kidney allografting. Cyclosporin A was given to sensitized rats in doses of 10 or 25 mg/kg/day for 14 days from the time of renal transplantation. Neither dose was nearly as effective in prolonging kidney graft survival in sensitized rats as the 10 mg/kg/day dose was in prolonging kidney graft survival in unsensitized rats. In the 25 mg/kg/day dose, cyclosporin A was capable of suppressing antibody formation to the graft in sensitized recipients despite the presence of donor-specific antibodies at the time of renal transplantation. The 10 mg/kg/day dose of cyclosporin A did not, however, suppress antibody formation after renal transplantation in sensitized recipients. In both sensitized and unsensitized rats cyclosporin A was effective in ameliorating the histological findings of arterial fibrinoid necrosis and glomerular necrosis in the renal allografts. In neither sensitized nor unsensitized rats did cyclosporin A effect the mononuclear cell infiltration of the renal allograft.