Chronic Renal Insufficiency Cohort (CRIC) Study

目的：我们建议采用多中心、前瞻性、队列设计，并进行标准化、开放性、结局变量评价 一项用于18-75岁慢性肾功能不全（CRI）患者（定义为125 I-碘酞酸盐）非实验性研究的技术 GFR 30-70cc/min/1.73m2。慢性肾功能不全队列研究的主要目标是：（1）确定 肾功能加速下降的因素;（2）评估心血管疾病（CVD）的发病率和危险因素。 方法：我们计划招募500例患者，其中至少30%为非洲裔美国人，50%患有糖尿病肾病。 我们将从我们的综合临床研究单位的12，729名预先筛选的CRI患者中招募研究参与者 包括：密歇根大学卫生系统（n= 5，807）;退伍军人事务医疗中心，安阿伯（n=358）;圣约翰 卫生系统，底特律（n= 1，430）;和健康计划，底特律（n= 5，134）。正在进行的临床研究工作的建议 研究小组（包括105名患者的CRI试点研究和AASK）记录了17.6%的总体参与潜力， 12，729例预筛选受试者，最终合并2，321例受试者。我们的招聘策略和保留/坚持 这些技术以前已经过测试，并在后勤上得到了完善。建议的主要结果变量是：（1）GFR的平均率 下降;（2）至终末期肾病（ESRD）的时间;（3）复合致死性和非致死性CVD事件;（4）全因死亡率。 待研究的关键解释变量包括：左心室成像（超声心动图）;颈动脉内膜/中膜厚度 （B型超声检查）;和心脏自主神经功能障碍（[“C”-羟麻黄碱{HED}正电子发射断层扫描）。所有关键 研究测量值将在一次24小时住院患者GCRC年度访视期间获得， 定期、间隔确定非访视程序。分析：为了分析效率，我们提出了一个分层的 招募方案允许广泛分布在整个入选GFR范围内。我们提出了一个两阶段的分析斜坡 包括患者内GFR斜率估计值和跨患者斜率分析，以评估 斜率分别采用重复测量分析和线性回归分析。将进行事件发生时间分析 直至ESRD、新发/复发性CVD事件或死亡，使用多变量Cox回归技术。将对3,000名患者进行抽样调查， 足以产生90%的把握度来检测小至平均值12%至15%的GFR下降率差异，并检测 事件（ESRD、死亡、CVD）发生率增加16%至40%。意义：本研究将改善 患者护理，并产生关于CRI进展和CVD并发症的潜在预测因子的新假设。最 这些假设的前景将需要在随机临床试验中进行检验。

AIMS: We propose the use of a multi-center, prospective, cohort design with standardized, open, outcome variable evaluation technique to non-experimentally study patients aged 18-75 years with chronic renal insufficiency (CRI) defined as125I-Iothalamate GFR 30-70cc/min/1.73m2. The primary goals of the Chronic Renal Insufficiency Cohort Study will be: (1) to determine the risk factors for accelerated decline in renal function; and (2) to evaluate the incidence and risk factors for cardiovascular disease (CVD). METHODS: We propose to recruit 500 patients of which at least 30% are African American and 50% have diabetic nephropathy. We will recruit the study participants from 12,729 prescreened patients with CRI from our integrated clinical research units consisting of: The University of Michigan Health System (n=5,807); Veteran Affairs Medical Center, Ann Arbor (n=358); St. Johns Health System, Detroit (n=l,430); and The Wellness Plan, Detroit (n=5,134). Ongoing clinicalresearch efforts of the proposing team (includingCRI Pilot Study of 105 patients and AASK) have documented an overall participationpotential of 17.6% in the 12,729 prescreened subjects which enables a final pool of 2,321 subjects. Our recruitment strategies and retention/adherence techniques have been previously tested and logistically refined. Proposed primary outcomes variables are: (1) the mean rate of GFR decline; (2) time to end stage renal disease (ESRD); (3) composite fatal and nonfatal CVD events; and (4) all-cause mortality rate. Key explanatory variables to be studied include: Left Ventricular imaging (Echocardiography); Carotid Intima/Media Thickness (B-mode ultrasonography); and Cardiac Dysautonomia (["C]-hydroxyephedrine {HED} Positron Emission Tomography). All key study measurements will be obtained during a single 24-hour in-patient GCRC yearly visit supplemented with standardized,regularly scheduled, interval ascertainment non-visit procedures. ANALYSIS PLAN: For analytic efficiency, we propose a stratified recruitment scheme that allows broad distributionover the entire inclusionGFR range. We propose a two-stage analysis of the slope of GFR consisting of within-patientGFR slope estimates and across-patient slope analysis to evaluate the determinants of variationin the slope using repeated measures analysis and linear regression analysis, respectively. Time to event analyses will be carried out until ESRD, de novo/recurrent CVD event or death using a multivariateCox regression technique. A sample of 3,000 patients will be sufficient to yield 90% power to detect differences in rates of decline of GFR as small as 12% to 15% of the mean, and to detect increases as small as 16% to 40% in the rates of events (ESRD, death, CVD). SIGNIFICANCE: This study will lead improved patient care and generate new hypotheses about potential predictors of CRI progression and CVD complications. The most promising of these hypotheses will require testing in randomized clinical trials.