Chronic Renal Insufficiency Cohort (CRIC) Study

目的：我们建议使用多中心、前瞻性、队列设计，并进行标准化、开放式、结果变量评估 18-75岁慢性肾功能不全(CRI)患者125I-异硫氰酸酯的非实验研究技术 GFR 30-70cc/min/1.73m2。慢性肾功能不全队列研究的主要目标是：(1)确定风险 (2)评估心血管疾病(CVD)的发病率和危险因素。 方法：我们建议招募500名患者，其中至少30%是非裔美国人，50%有糖尿病肾病。 我们将从12,729名CRI患者中招募研究参与者，这些患者来自我们的综合临床研究单位 包括：密歇根大学卫生系统(n=5,807)；安娜堡退伍军人事务医疗中心(n=358)；圣约翰斯 卫生系统，底特律(n=L，430)；健康计划，底特律(n=5,134)。正在进行的临床研究工作的建议 团队(包括对105名患者和AASK的CRI试点研究)记录了在 12,729名经过预筛选的受试者，最终共有2,321名受试者。我们的招聘策略和留任/遵守 这些技术之前已经过测试，并在后勤方面进行了改进。建议的主要结果变量是：(1)GFR的平均比率 (2)终末期肾病(ESRD)；(3)复合致命性和非致命性心血管事件；(4)全因死亡率。 需要研究的主要解释变量包括：左心室成像(超声心动图)；颈动脉内膜/中层厚度 (B超)；和心脏自主神经障碍([“C]-羟基麻黄碱正电子发射断层扫描)。所有关键 研究测量将在一次24小时住院的GCRC年度访问中获得，并辅之以标准化的、定期的 预定的、间隔确定的非探视程序。分析计划：为了提高分析效率，我们提出了分层 招聘计划，允许在整个纳入GFR范围内进行广泛分配。我们建议对斜坡进行两个阶段的分析 由患者内GFR斜率估计和患者间斜率分析组成的GFR评估变异的决定因素 对坡度分别采用重复测量分析和线性回归分析。将执行到事件的时间分析 使用多变量Cox回归技术，直到终末期肾病、新发/复发的CVD事件或死亡。3000名患者的样本将是 足以产生90%的功率来检测GFR下降率的差异，小到平均值的12%到15%，并检测到 事件(终末期肾病、死亡、心血管疾病)的发生率增加16%至40%。意义：这项研究将导致改进 患者护理，并产生关于CRI进展和CVD并发症的潜在预测因素的新假设。最多的 这些假设的前景将需要在随机临床试验中进行测试。

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.