雷帕霉素联合环孢素和皮质类固醇预防肾移植急性排斥反应的临床研究

An open-label multi-center clinical study of the efficacy and safety of rapamycin in combination with CsA and steroid to prevent the acute rejection of kidney transplantation

目的 探讨雷帕霉素 (rapamycin ,RPM)联合环孢素和皮质类固醇预防肾移植急性排斥(AR)的临床疗效和安全性。方法 来自国内四家移植中心的首次尸体肾移植患者共 10 0例 ,免疫抑制疗法为RPM联合CsA和皮质类固醇。移植后 4 8h内开始服用RPM ,首次负荷剂量为 6mg/d,维持剂量为 2mg/d。结果 随访 6个月以上 84例 ,提前中止治疗 16例。发生AR 8例 ,7例经MP冲击治疗后逆转 ,其中 6例仍维持RPM 2mg/d的治疗 ,另 1例改为RPM 3mg/d ,继续随访半年以上 ,未见AR复发。不良反应有高脂血症 (占 4 7% )、肝功能异常 (占 2 7% )等。结论 RPM联合CsA和皮质类固醇预防移植肾排斥的临床疗效肯定 ,AR发生率低 ,但高脂血症和肝功能异常发生率高。长期疗效有待进一步观察和研究。

Objective To study the clinical efficacy and safety of rapamycin in combination with CsA and steroid to prevent the acute rejection of kidney transplantation. Methods In an open-label,multi-center study,there were 100 primary renal allograft recipients with cadaveric donors enrolled from 4 transplantation centers in China. The immunosuppressive regimen was the triple therapy of rapamycin in combination with CsA and steriod. Rapamycin was administered in 48 h after grafting. The first dose of rapamycin was 6 mg /day and the maintenance dose was 2 mg /day. Results Eighty-four recipients were followed up for more than 6 months. Rapamycin was discontinued in 16 patients because of the adverse events and other reasons. Eight patients experienced acute rejection and 7 patients were reversed by methyprednisolon therapy. In 6 of the 7 patients,the dose of rapamycin was maintained 2 mg /day. The remaining one was added to 3 mg /day. No recurrence of AR was observed in a continuous follow-up of more than half-year. The most common and significant adverse events were hyperlipoidemia and abnormal liver function.Conclusions The combination of rapamycin with CsA and steroid to treat recipients of kidney transplantation is safe and efficient. There was a low incidence of AR but a high incidence of hyperlipoidemia and abnormal liver function. The rational regulation of the dose may reduce the incidence of the side-effects. Further observation and study are required for long-term application.