Lisik W, Schoenberg L, Lasky R E, Kahan B D
Division of Immunology and Organ Transplantation, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Transplant Proc. 2007 Dec;39(10):3086-92. doi: 10.1016/j.transproceed.2007.10.008.
Statins offer a strategy to address dyslipidemia commonly experienced by immunosuppressed transplant recipients.
This single-center, retrospective study of 325 recipients (mean posttransplant follow-up of over 6 years; 75.0+/-26.0 months) correlated four adverse outcomes-biopsy-confirmed acute rejection episodes, biopsy-confirmed chronic rejection/allograft nephropathy, graft loss, or death-with demographic and posttreatment variables. Patients were treated with a combination of sirolimus (SRL), cyclosporine (CsA), and various durations of steroids. Statins were prescribed for 259/325 (79%) recipients whose serum cholesterol exceeded 240 mg/dL and discontinued when the creatine phosphokinase increased fivefold (3.4%) or the liver function, threefold (3.0%) above normal.
Upon univariate (hazard ratio [HR] 0.16; P<.001) and multivariate analysis (HR 0.38; P=.02), statins were markedly protective against acute rejection episodes. They reduced occurrence of chronic nephropathy/chronic rejection (HR 0.60; P=.03 and HR 0.52; P=.01, respectively). Incidences of graft loss were diminished (HR 0.26; P<.001 and HR 0.49; P=.01, respectively). Finally, the mortality rate was decreased (HR 0.21, P=.001 and HR 0.26, P=.01, respectively). Upon multivariate analysis, a reduced incidence of acute rejection was correlated with greater exposure to SRL (HR 0.78, P=.016) and CsA (HR 0.39; P=.006).
This study demonstrated compelling effects of statins against all adverse outcomes among patients treated with SRL-based, CsA-containing regimens. The profoundly dyslipidemic properties of SRL may explain these unique findings compared with previous studies on patients treated with CsA-based regimens.
他汀类药物为解决免疫抑制的移植受者常见的血脂异常问题提供了一种策略。
这项对325名受者进行的单中心回顾性研究（移植后平均随访超过6年；75.0±26.0个月）将四项不良结局——活检证实的急性排斥反应发作、活检证实的慢性排斥反应/移植肾肾病、移植肾丢失或死亡——与人口统计学和治疗后变量相关联。患者接受西罗莫司（SRL）、环孢素（CsA）联合不同疗程的类固醇治疗。259/325（79%）血清胆固醇超过240mg/dL的受者服用了他汀类药物，当肌酸磷酸激酶升高五倍（3.4%）或肝功能高于正常水平三倍（3.0%）时停药。
单因素分析（风险比[HR]0.16；P<0.001）和多因素分析（HR 0.38；P = 0.02）显示，他汀类药物对急性排斥反应发作具有显著的保护作用。它们降低了慢性肾病/慢性排斥反应的发生率（HR分别为0.60；P = 0.03和HR 0.52；P = －0.01）。移植肾丢失的发生率降低（HR分别为0.26；P<0.001和HR 0.49；P = 0.01）。最后，死亡率降低（HR分别为0.21，P = 0.001和HR 0.26，P = 0.01）。多因素分析显示，急性排斥反应发生率降低与更多地使用SRL（HR 0.78，P = 0.016）和CsA（HR 0.39；P = 0.006）相关。
本研究证明了他汀类药物对接受基于SRL、含CsA方案治疗的患者的所有不良结局都有显著效果。与之前对接受基于CsA方案治疗的患者的研究相比，SRL严重的血脂异常特性可能解释了这些独特的发现。
