Nephrotoxicity has limited the effectiveness of
cyclosporine in
transplantation therapy and has precipitated the need to develop a new
immunosuppressive agent that lacks this nephrotoxicity or has a higher therapeutic index. Prior studies have suggested that
cyclosporin G may be equally effective immunosuppressively, but less nephrotoxic than
cyclosporine. To compare the immunosuppressive effects of the two agents, graft survival was analyzed in Lewis-Brown Norway rats, which received heterotopic ACl heart allografts and were treated orally with
cyclosporin G or
cyclosporine at 5 and 10 mg/kg/day. To compare nephrotoxicity the group of rats that had
transplantations and an additional group of surgically intact Lewis-Brown Norway rats, treated orally with
cyclosporin G or
cyclosporine at dosages ranging from 10 to 50 mg/kg/day and for durations ranging from 50 to 180 days, were analyzed in terms of kidney morphology (
fibrosis, glomerular damage, interstitial infiltrate, and tubular dilation) and kidney function (blood
urea nitrogen and serum
creatinine levels) in this model
cyclosporin G was significantly less effective than
cyclosporine in prolonging graft survival at 5 mg/kg/day but equally effective
at 10 mg/kg/day. In addition,
cyclosporin G was substantially less nephrotoxic both morphologically and functionally at low (10 mg/kg/day) and high (50 mg/kg/day) dosages. Further studies are indicated to determine the therapeutic index of
cyclosporin G and to evaluate its use in combination with other
immunosuppressive agents.