Hernández Domingo, Miquel Rosa, Porrini Esteban, Fernández Ana, González-Posada José Manuel, Hortal Luis, Checa María Dolores, Rodríguez Aurelio, García José Javier, Rufino Margarita, Torres Armando
Nephrology Section and Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
Transplantation. 2007 Sep 27;84(6):706-14. doi: 10.1097/01.tp.0000282872.17024.b7.
Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown.
This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups.
A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008).
Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.
基于低剂量环孢素A（CsA）或他克莫司（TAC）的免疫抑制方案可能会改善肾移植（KT）后的短期预后，但目前尚不清楚最佳的免疫抑制方案。
本研究比较了两种减少钙调神经磷酸酶抑制剂（CNIs）暴露的免疫抑制方案与标准剂量CsA在240例患者中的24个月疗效和安全性，这些患者被随机分为三组：A组（n = 80）：抗胸腺细胞球蛋白、CsA（4mg/kg，每日两次）加硫唑嘌呤（1.5mg/kg，每日一次）；B组（n = 80）：巴利昔单抗、CsA（2mg/kg，每日两次）加霉酚酸酯（MMF；1g，每日两次）；C组（n = 80）：巴利昔单抗、TAC（0.05mg/kg，每日两次）加MMF（1g，每日两次）。所有组的类固醇给药方式相同。
根据Cockcroft-Gault公式（57±12、65.2±20、73.5±27ml/min，P = 0.044）、Jelliffe-2公式（51.5±16、56±19、59.4±19ml/min/1.73m²，P = 0.041）和肾脏病饮食改良公式（53±17、58.5±20、61.6±22ml/min/1.73m²，P = 0.035）估算，C组在12个月时的肌酐清除率显著优于A组。B组和C组之间未观察到显著差异。各组经活检证实的急性排斥反应发生率相似（15%、13.8%和16.3%）。此外，各组在24个月时的患者和移植物存活率无差异。各组的不良反应相似，但A组的巨细胞病毒感染率显著更高（41%对20%对25%；P = 0.008）。
与肾移植后标准剂量的CsA相比，减少CNIs暴露的免疫抑制方案在肾功能保护方面相似，且不会导致免疫抑制不足。
