Sterneck Martina, Kaiser Gernot M, Heyne Nils, Richter Nicolas, Rauchfuss Falk, Pascher Andreas, Schemmer Peter, Fischer Lutz, Klein Christian G, Nadalin Silvio, Lehner Frank, Settmacher Utz, Gotthardt Daniel, Loss Martin, Ladenburger Stephan, Wimmer Peter, Dworak Markus, Schlitt Hans J
Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of General, Visceral and Transplantation Surgery, Essen University Hospital, Essen, Germany.
Clin Transplant. 2016 Jun;30(6):741-8. doi: 10.1111/ctr.12744. Epub 2016 May 10.
The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data.
PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment.
A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively.
Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.
为期12个月的PROTECT研究表明，从基于钙调神经磷酸酶抑制剂（CNI）的免疫抑制方案转换为基于无CNI的依维莫司（EVR）方案的初发肝移植受者（LTxR），其肾功能在数值上表现更好。在此，我们展示5年随访数据。
PROTECT是一项随机对照研究，其中LTxR接受巴利昔单抗和基于CNI的免疫抑制±皮质类固醇。患者按1:1随机分组，接受EVR或继续使用CNI。完成核心研究的患者可进入其随机治疗的扩展研究。
共有81例患者进入扩展研究（41例接受EVR；40例接受CNI）。随机分组后第59个月时，EVR组的校正平均估算肾小球滤过率（eGFR）显著更高，使用Cockcroft-Gault公式得出的获益为12.4 mL/分钟（95%可信区间：1.2；23.6；p = 0.0301）。同样，使用四变量肾病饮食改良（MDRD4）公式或Nankivell公式时，校正和未校正的eGFR均有显著获益。在扩展期，治疗失败率相似。严重不良事件（SAE）分别发生在EVR组的26例（63.4%）和CNI组的28例（70.0%）患者中。
与基于CNI的治疗相比，基于EVR的无CNI免疫抑制在5年随访后导致肾功能显著更好，且患者和移植物结局相当。
