University of Florida, Gainesville, FL, USA.
Am J Transplant. 2012 Mar;12(3):694-705. doi: 10.1111/j.1600-6143.2011.03919.x. Epub 2012 Jan 10.
A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.
一项大型前瞻性、开放性、随机试验评估了钙调神经磷酸酶抑制剂（CNI）到西罗莫司（SRL）转换在肝移植患者中维持肾功能的作用。符合条件的患者在 6-144 个月前接受了肝移植，并在早期移植后接受 CNI（环孢素或他克莫司）维持免疫抑制。共有 607 名患者被随机分为（2:1）两组，一组（n=393）在 24 小时内从 CNI 突然转换为 SRL，另一组（n=214）继续使用 CNI 治疗长达 6 年。在 12 个月（主要疗效终点）时，两组患者的基础调整后的平均 Cockcroft-Gault GFR 变化没有显著差异。主要安全性终点（12 个月时移植失败或死亡的累积发生率非劣效性）未达到（SRL 组为 6.6%，CNI 组为 5.6%）。12 个月时死亡率无显著差异，且在 12 个月期间未观察到真正的移植失败（例如肝移植）。在 52 周时，SRL 转换与更高的活检证实急性排斥反应发生率（p=0.02）和停药率（p<0.001）相关，主要是由于不良事件。不良事件与已知的安全性特征一致。总之，在 CNI 转换为 SRL 免疫抑制后 1 年，肝移植患者没有表现出明显的获益。
