Prospective Renal Insufficiency Cohort Evaluation:PRICE

慢性肾功能不全(CRI)通常进展为终末期肾病(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受试者CVD的发展和进展。为了解决这一假设，我们提出了两个具体的目标：1)确定CRI进展的危险因素，包括进展对临床、遗传和体液因素的依赖；2)确定临床、遗传和体液危险因素在CRI患者心血管疾病发展和进展中的作用。详细的计划介绍了我们将如何通过我们中心现有的和正在运行的数据库来识别和访问合格的受试者。对这个数据库的查询发现了4000多名符合条件的受试者，其中男性的肌酐标准为&gt；或=1.7 mg/dl，女性为&gt；或=1.4 mg/dl(在此基础上，我们施加了额外的限制，要求两个肌酸值至少相隔90天)。利用数据库的结果，进行了一项试点征聘研究。我们联系了来自两个初级保健诊所的33名代表性受试者。33名受试者中有14名(42%；95%可信区间为25%-61%)不合格地表示他们将参与我们在本申请中提出的方案，另有4名受试者在与他们的PCP进一步讨论后表示他们可能会参与。因此，我们预计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急诊室和学生经营的健康诊所识别和联系CRI服务不足的受试者的方法。对于Aim#L，我们提出了一项招生战略，以确保有足够的性别、种族和肾脏疾病代表。在目标1中，我们为CRI进展提供了详细的核GFR方法和终点，以及为RFA的主要和次要目标服务的病史、体检、实验室、生活质量和成像程序。我们建议测量特定的炎症、生长、细胞因子、脂蛋白、氧化应激、降钙和血流动力学因素，显示它们纳入的理由以及它们促进CRI和CVD的机制。对于第二个目标，我们提出了具体的心血管疾病定义，以及提供了三种心血管疾病患病率测量(颈动脉IMT厚度、超声心动图和EBCT)和两种心血管疾病进展(颈动脉IMT厚度、超声心动图)的成像策略。在我们经验丰富的临床中心收集的关于拟议的临床、遗传和体液因素的数据将大大有助于了解CRI和CRI受试者的心血管疾病。

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..