Knoll Greg A, Cantarovitch Marcelo, Cole Ed, Gill John, Gourishankar Sita, Holland Dave, Kiberd Bryce, Muirhead Norman, Prasad Ramesh, Tibbles Lee Anne, Treleaven Darin, Fergusson Dean
Division of Nephrology, Kidney Research Center, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Nephrol Dial Transplant. 2008 Jan;23(1):354-8. doi: 10.1093/ndt/gfm574. Epub 2007 Sep 10.
In non-transplant patients with chronic kidney disease and proteinuria, inhibition of the renin-angiotensin system with an ACE-inhibitor or an angiotensin receptor blocker has been shown to delay the progression of renal disease. Observational studies in the kidney transplant population have produced conflicting results with some studies showing benefit and others no benefit of renin-angiotensin system blockade.
This report describes the design and methodological issues of a randomized controlled trial evaluating the effect of ramipril in a renal transplant population. This study has been funded by a peer-reviewed grant from the Canadian Institutes of Health Research and is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN-78129473).
The study will randomize 528 kidney transplant patients (11 Canadian centers) with proteinuria and an estimated GFR between 20 and 55 ml/min/1.73 m(2) to either ramipril (5 mg BID) or placebo. Patients, clinical staff and investigators will be blinded to treatment allocation. The primary outcome will be a composite measure incorporating doubling of serum creatinine, end stage renal disease or death. Principal secondary outcomes include: decline in GFR using a radioisotopic method, change in proteinuria, change in blood pressure, incidence of adverse events (e.g. hyperkalemia, anemia), incidence of cardiovascular events and health-related quality of life assessed by the Short Form-36 and the EuroQol-5D.
Upon completion, this trial will provide clinically meaningful evidence about whether treatment with an ACE-inhibitor will reduce patient mortality and prolong allograft survival in renal transplant recipients.
在患有慢性肾病和蛋白尿的非移植患者中，使用血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂抑制肾素 - 血管紧张素系统已被证明可延缓肾病进展。对肾移植人群的观察性研究结果相互矛盾，一些研究显示肾素 - 血管紧张素系统阻断有益，而另一些则未发现益处。
本报告描述了一项评估雷米普利对肾移植人群疗效的随机对照试验的设计和方法学问题。本研究由加拿大卫生研究院的同行评审拨款资助，并已在国际标准随机对照试验编号注册中心（ISRCTN - 78129473）注册。
该研究将把528例患有蛋白尿且估计肾小球滤过率（GFR）在20至55 ml/min/1.73 m²之间的肾移植患者（来自11个加拿大中心）随机分为雷米普利组（5 mg，每日两次）或安慰剂组。患者、临床工作人员和研究人员将对治疗分配情况不知情。主要结局将是一个综合指标，包括血清肌酐翻倍、终末期肾病或死亡。主要次要结局包括：使用放射性同位素方法测定的GFR下降、蛋白尿变化、血压变化、不良事件发生率（如高钾血症、贫血）、心血管事件发生率以及通过简短健康调查问卷（SF - 36）和欧洲五维健康量表（EuroQol - 5D）评估的健康相关生活质量。
本试验完成后，将提供关于ACEI治疗是否能降低肾移植受者的患者死亡率并延长移植肾存活时间的具有临床意义的证据。
