Ruggenenti Piero, Codreanu Igor, Cravedi Paolo, Perna Annalisa, Gotti Eliana, Remuzzi Giuseppe
Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy.
Clin J Am Soc Nephrol. 2006 May;1(3):546-54. doi: 10.2215/CJN.01841105. Epub 2006 Mar 1.
In high-risk kidney transplant recipients, induction therapy with rabbit anti-human thymocyte globulin (RATG) reduces the risk for acute rejection but is associated with significant toxicity, opportunistic infections, and cancer. Using reduced doses of RATG combined with anti-IL-2 antibodies may achieve the same antirejection activity of standard-dose RATG but with a better safety profile. This randomized, open-label study compared the efficacy, tolerability, and costs of low-dose RATG (0.5 mg/kg per d) plus basiliximab (20 mg 4 d apart) versus standard-dose RATG (2 mg/kg per d) in 33 consecutive high-risk renal transplant recipients (living-related transplant recipients, sensitized patients or patients who received another transplant, and patients with delayed graft function) over 6 mo of follow-up. All patients received concomitant therapy with steroids, cyclosporin A, and azathioprine or mycophenolate mofetil. Seventeen patients received low-dose RATG plus basiliximab, and 16 received standard-dose RATG. Patient (100 versus 100%) and graft (94 versus 100%) survival were comparable in the two groups, but the incidence of fever (17.6 versus 56.5%; P = 0.01), leukopenia (23.5 versus 56.3%; P < 0.05), anemia (29.4 versus 62.5%; P < 0.05), cytomegalovirus reactivations (17.6 versus 56.5%; P = 0.01), the number of transfused units (0.5 +/- 0.9 versus 2.0 +/- 2.4; P < 0.001), and treatment costs (3652 +/- 704 versus 5400 +/- 1960 euro; P = 0.001) were lower with low-dose RATG plus basiliximab than with standard-dose RATG. There was one episode of biopsy-proven acute rejection on low-dose RATG plus basiliximab, and there were two on standard-dose RATG. In renal transplantation, induction therapy with basiliximab plus low-dose RATG effectively prevents acute rejection and is safer and more cost-effective than induction with standard-dose RATG.
在高风险肾移植受者中，使用兔抗人胸腺细胞球蛋白（RATG）进行诱导治疗可降低急性排斥反应的风险，但会伴有显著的毒性、机会性感染和癌症风险。采用低剂量RATG联合抗IL-2抗体或许能达到与标准剂量RATG相同的抗排斥活性，但安全性更佳。这项随机、开放标签研究比较了低剂量RATG（每日0.5 mg/kg）加巴利昔单抗（20 mg，间隔4天）与标准剂量RATG（每日2 mg/kg）在33例连续高风险肾移植受者（活体亲属移植受者、致敏患者或接受过另一次移植的患者以及移植肾功能延迟的患者）中的疗效、耐受性和成本，随访时间为6个月。所有患者均接受了类固醇、环孢素A和硫唑嘌呤或霉酚酸酯的联合治疗。17例患者接受低剂量RATG加巴利昔单抗治疗，16例接受标准剂量RATG治疗。两组患者的生存率（100%对100%）和移植肾生存率（94%对100%）相当，但低剂量RATG加巴利昔单抗组的发热发生率（17.6%对56.5%；P = 0.01）、白细胞减少症发生率（23.5%对56.3%；P < 0.05）、贫血发生率（29.4%对62.5%；P < 0.05）、巨细胞病毒再激活率（17.6%对56.5%；P = 0.01）、输注单位数量（0.5±0.9对2.0±2.4；P < 0.001）以及治疗成本（3652±704对5400±1960欧元；P = 0.001）均低于标准剂量RATG组。低剂量RATG加巴利昔单抗组有1例经活检证实的急性排斥反应，标准剂量RATG组有2例。在肾移植中，巴利昔单抗加低剂量RATG进行诱导治疗可有效预防急性排斥反应，且比标准剂量RATG诱导治疗更安全、更具成本效益。
