RS-61443 reverses acute allograft rejection in dogs.
RS-61443, a morpholinoethyl ester of mycophenolic acid, has been shown to prevent renal allograft rejection in dogs when administered in combination with low-dose cyclosporine and prednisolone. The purpose of this study was to test whether high-dose RS-61443 can reverse acute renal allograft rejection. Mongrel dogs receiving a renal allograft were treated with baseline immunosuppression consisting of RS-61443 10 mg/kg, cyclosporine 5 mg/kg, and prednisolone 0.1 mg/kg. All animals developed acute allograft rejection. Dogs in group I (n = 11) received 14, 7, and 3.5 mg/kg methylprednisolone intravenously on 3 consecutive days after the diagnosis of rejection. Dogs in group II (n = 16) were given RS-61443 80 mg/kg twice daily. After rejection treatment, RS-61443 was increased to 20 mg/kg in all animals; cyclosporine and prednisolone were continued as before. In group I, five of 11 dogs developed uncontrollable rejection; in six of 11 dogs only a temporary reversal occurred. None of the dogs in group I survived for more than 20 days after the diagnosis of rejection. In group II rejection was completely reversed in 14 of 16 dogs (87.5%), resulting in a return of serum creatinine to prerejection levels. Thus, high-dose therapy with RS-61443 can successfully reverse acute kidney allograft rejection in dogs in a high proportion of cases.
Platz
K P
KP
Department of Surgery, University of Wisconsin School of Medicine, Madison 53792.
Bechstein
W O
WO
Eckhoff
D E
DE
Suzuki
Y
Y
Sollinger
H W
HW
D000818:Animals; D001706:Biopsy; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000187:drug effects*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D014184:Transplantation, Homologous
D003404:Creatinine; D009173:Mycophenolic Acid