Platz K P, Bechstein W O, Eckhoff D E, Suzuki Y, Sollinger H W
Department of Surgery, University of Wisconsin School of Medicine, Madison 53792.
Surgery. 1991 Oct;110(4):736-40; discussion 740-1.
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.
霉酚酸吗啉乙酯（RS - 61443）已被证明，与低剂量环孢素和泼尼松龙联合使用时，可预防犬肾移植排斥反应。本研究的目的是测试高剂量RS - 61443是否能逆转急性肾移植排斥反应。接受肾移植的杂种犬接受由10mg/kg RS - 61443、5mg/kg环孢素和0.1mg/kg泼尼松龙组成的基线免疫抑制治疗。所有动物均发生急性移植排斥反应。I组（n = 11）的犬在诊断出排斥反应后连续3天静脉注射14mg/kg、7mg/kg和3.5mg/kg甲泼尼龙。II组（n = 16）的犬每天两次给予80mg/kg RS - 61443。排斥反应治疗后，所有动物的RS - 61443增加至20mg/kg；环孢素和泼尼松龙继续按以前的剂量使用。I组中，11只犬中有5只发生了无法控制的排斥反应；11只犬中有6只仅出现了暂时的逆转。I组中没有一只犬在诊断出排斥反应后存活超过20天。II组中，16只犬中有14只（87.5%）的排斥反应完全逆转，血清肌酐恢复到排斥反应前的水平。因此，高剂量RS - 61443治疗可在很大比例的犬中成功逆转急性肾移植排斥反应。
