Prospective Renal Insufficiency Cohort Evaluation:PRICE

慢性肾功能不全（CRI）经常发展为终末期肾病（ESRD），心血管疾病（CVD）的患病率和病死率增加。我们假设CRI的进展是由临床、遗传和体液因素解释的，这些因素也有助于CRI患者CVD的发生和进展。为了解决这一假设，我们提出了两个具体目标：#1)确定CRI进展的危险因素，包括对临床、遗传和体液因素的依赖；#2)确定CRI受试者中CVD发生和进展的临床、遗传和体液危险因素的作用。详细的计划将介绍我们如何通过我们中心现有的和正常运行的数据库识别和访问符合条件的受试者。通过对该数据库的查询，男性的肌酐标准为>或= 1.7 mg/dl，女性为>或= 1.4 mg/dl（在此基础上，我们增加了两个肌酐值至少间隔90天的额外限制），确定了4000多名符合条件的受试者。利用数据库的结果进行了一项试点征聘研究。我们联系了来自两家初级保健机构的33名代表性受试者。33名受试者中有14名（42%;95% CI 25-61%）给出了不确定的“是”，他们将参加我们在本申请中提出的方案，另外4名受试者表示他们在与PCP进一步讨论后“可能”参加。因此，我们计划在我们的卫生系统中已经确定了足够数量的自愿受试者。接下来，我们描述了通过我们的ED和学生经营的健康诊所识别和联系服务不足的CRI受试者的方法。对于目标1，我们提出了一种确保充分的性别、种族和肾脏疾病代表性的入组策略。在目标1中，我们提供了详细的核GFR方法和CRI进展的终点，以及历史，体格检查，实验室，生活质量和成像程序，服务于RFA的主要和次要目标。我们建议测量特定的炎症、生长、细胞因子、脂蛋白、氧化应激、钙化和血流动力学因子，以显示它们的包涵原理和它们促进CRI和CVD的机制。对于目标#2，我们提出了具体的CVD定义，以及一种成像策略，该策略提供了CVD患病率的三种测量方法（颈动脉IMT厚度、超声心动图和EBCT）和CVD进展的两种测量方法（颈动脉IMT厚度、超声心动图）。在我们经验丰富的临床中心收集的关于建议的临床、遗传和体液因素的数据将大大有助于了解CRI和CRI患者的心血管疾病。

Chronic Renal Insufficiency (CRI) often progresses to End Stage Renal Disease (ESRD), with an increased prevalence and fatality from Cardiovascular Disease (CVD). We hypothesize that CRI progression is explained by clinical, genetic and humoral factors which also contribute to development and progression of CVD in subjects with CRI. To address this hypothesis we propose two specific Aims: #1) To determine risk factors for the progression of CRI, including the dependence of progression upon clinical, genetic and humoral factors, and #2) To determine the role of clinical, genetic and humoral risk factors for the development and progression of CVD in subjects with CRI. Detailed plans are presented for how we will identify and access eligible subjects via an existing and functioning database at our Center. A query of this database with the creatinine criteria of > or = 1.7 mg/dl for men and > or = 1.4 mg/dl for women (upon which we imposed the additional constraint of requiring two creatinine values at least 90 days apart) identified more than 4,000 eligible subjects. Using the database results a pilot recruitment study was undertaken. We contacted 33 representative subjects from two Primary Care practices. Fourteen of 33 subjects (42%; 95% CI 25-61%) gave an unqualified 'yes' they would participate in the protocol we propose in this application, and another 4 subjects indicated they would 'probably' participate after discussing it further with their PCP. Thus, we project an adequate number of willing subjects already identified within our Health System. Next, we describe methods for identifying and contacting under-served subjects with CRI through our ED and student-run health clinics. For Aim #l we present an enrollment strategy assuring adequate gender, ethnicity and renal disease representation. In Aim #1 we provide detailed nuclear GFR methods and endpoints for CRI progression, along with historical, physical exam, laboratory, quality-of-life and imaging procedures that serve the primary and secondary goals of the RFA. We propose measurement of specific inflammatory, growth, cytokine, lipoprotein, oxidative stress, calcitropic and hemodynamic factors showing their rationale for inclusion and mechanisms by which they contribute to CRI and CVD. For Aim #2 we present specific CVD definitions, and an imaging strategy that provides three measures of CVD prevalence (carotid IMT thickness, echocardiogram and EBCT) and two measures of CVD progression (carotid IMT thickness, echocardiogram). The data collected on the proposed clinical, genetic and humoral factors at our experienced Clinical Center will contribute substantially to the understanding of CRI, and CVD in subjects with CRI..