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Dose and time response studies of the new immunosuppressive agent, cyclosporin A, have been performed in a dog renal allograft model. Rejection of a renal allograft only occurred in one of six dogs receiving 20 mg/kg/day continuously, but in 10 of 11 dogs receiving 10 mg/kg/day. Doses of 10 or 20 mg/kg/day given for 2 or 3 weeks delayed rejection, but rejection occurred in all animals when the drug was stopped. This suggests that the drug does not produce clonal deletion of the lymphocytes engaged in the immune reaction against the graft, but merely their suppression. The histological picture of rejection was markedly improved by therapeutic doses of cyclosporin A. No consistent histological or biochemical evidence for heptatoxicity or nephrotoxicity was found even in the higher doses tested. One fatal and four non-fatal infectious complications were seen in 29 dogs receiving doses of 5 mg/kg/day or higher.
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