Saudek Frantisek, Malaise Jacques, Boucek Petr, Adamec Milos
Institute for Clinical and Experimental Medicine, Diabetes Center, Prague, Czech Republic.
Nephrol Dial Transplant. 2005 May;20 Suppl 2:ii3-10, ii62. doi: 10.1093/ndt/gfh1076.
Single-centre and retrospective studies suggest superiority of tacrolimus over cyclosporin as cornerstone immunosuppressive therapy for simultaneous pancreas-kidney (SPK) transplantation. This open-label, multicentre trial compared the efficacy and safety of tacrolimus with cyclosporin microemulsion (ME) in diabetic patients with end-stage renal disease undergoing their first cadaveric SPK transplantation. The 3-year results are reported.
Patients were recruited from 10 centres in Europe and one centre in Israel: 103 were randomized to receive tacrolimus (initial dose: 0.2 mg/kg/day p.o.) and 102 to cyclosporin-ME (7 mg/kg/day p.o.). All patients received concomitant rabbit anti-T-cell globulin induction, mycophenolate mofetil (MMF) and short-term corticosteroids.
Fewer patients receiving tacrolimus (36.9%) than cyclosporin-ME (57.8%) were discontinued from treatment (P = 0.003). The initial episodes of biopsy-proven rejection were moderate or severe in just one out of 31 (3%) tacrolimus-treated patients compared with 11 out of 39 (28%) patients receiving cyclosporin-ME (P = 0.009). While 3-year patient and kidney survival rates were similar in the two treatment groups, pancreas survival was superior with tacrolimus (89.2 vs 72.4%; P = 0.002). Thrombosis resulted in pancreas graft loss in 10 patients receiving cyclosporin-ME and in only two treated with tacrolimus (P = 0.02). Overall adverse event frequency was similar in both groups, but MMF intolerance was more frequent with tacrolimus and hyperlipidaemia more frequent with cyclosporin-ME.
In this 3-year study, tacrolimus was more effective than cyclosporin-ME in preventing moderate or severe kidney or pancreas rejection after SPK transplantation. It also provided superior pancreas survival and reduced the risk of pancreas graft thrombosis.
单中心回顾性研究表明，在同期胰肾联合移植（SPK）中，他克莫司作为基础免疫抑制疗法优于环孢素。本开放标签多中心试验比较了他克莫司与环孢素微乳剂（ME）在首次接受尸体供肾SPK移植的终末期肾病糖尿病患者中的疗效和安全性。本文报告了3年的研究结果。
患者来自欧洲的10个中心和以色列的1个中心：103例患者随机接受他克莫司治疗（初始剂量：口服0.2mg/kg/天），102例接受环孢素-ME治疗（口服7mg/kg/天）。所有患者均接受兔抗T细胞球蛋白诱导治疗、霉酚酸酯（MMF）和短期糖皮质激素治疗。
接受他克莫司治疗的患者（36.9%）停药的人数少于接受环孢素-ME治疗的患者（57.8%）（P = 0.003）。在31例接受他克莫司治疗的患者中，只有1例（3%）经活检证实的首次排斥反应为中度或重度，而在39例接受环孢素-ME治疗的患者中有11例（28%）出现此类情况（P = 0.009）。虽然两个治疗组的3年患者生存率和肾脏生存率相似，但他克莫司治疗组的胰腺生存率更高（89.2%对72.4%；P = 0.002）。10例接受环孢素-ME治疗的患者因血栓形成导致胰腺移植失败，而接受他克莫司治疗的患者只有2例（P = 0.02）。两组的总体不良事件发生率相似，但他克莫司治疗组MMF不耐受的情况更常见，环孢素-ME治疗组高脂血症更常见。
在这项为期3年的研究中，他克莫司在预防SPK移植后中度或重度肾脏或胰腺排斥反应方面比环孢素-ME更有效。它还能提高胰腺生存率，并降低胰腺移植血栓形成的风险。
