Pulse wave velocity in chronic kidney diseases

描述（由申请人提供）：国家糖尿病、消化和肾脏疾病研究所（NIDDK）于2001年建立了慢性肾功能不全队列研究。CRIC研究的主要目标是检查慢性肾脏病（CKD）进展（即肾功能进一步丧失）和不同严重程度CKD患者心血管事件的风险因素，并开发预测模型，以识别CKD高风险亚组。后者的结果将针对高风险受试者入组未来的治疗试验，并增加可用预防治疗的应用。高血压治疗是一种有效的干预措施，可以改变CKD患者肾功能丧失的过程。然而，非裔美国人肾脏疾病研究的最新发现表明，尽管使用阻断肾素-血管紧张素系统的方案控制了血压，但仍会发生肾功能丧失和心血管事件。这就提出了一种可能性，即除了降低血压之外，还需要采取干预措施来阻止CKD的进展并预防心血管疾病（CVD）。现有数据表明，大动脉僵硬度在肾功能不全和CVD中起作用。主动脉脉搏波速度（PWV;大动脉僵硬度的金标准测量）和中心脉压的测定是新的方法，在心血管疾病流行病学中提供了有用的信息。我们建议使用这些方法在已经招募的CRIC人群中研究CVD以及进行性肾功能丧失，预计这将有助于缩小血管功能和肾脏/心血管结局之间的知识差距。我们假设主动脉脉搏波速度预测CKD患者的肾脏和CVD结局。我们提出用三个具体目标来检验这一假设：具体目标1：确定慢性肾脏疾病受试者异质队列中的脉搏波速度。具体目标2：确定脉搏波传导速度在CKD队列中预测肾衰竭进展的效用。具体目标3：确定脉搏波速度预测CKD队列心血管结局的效用。从2003年开始，这些目标将在美国临床中心招募的3000名患者中实施，其中50%患有糖尿病。本研究的所有数据均由宾夕法尼亚大学科学数据协调中心（SDCC）管理。所采用的技术涉及对受试者的最小风险和适度的执行时间负担。肾功能和CVD是CRIC中仔细测量的预先指定的终点。提高对CKD进展和心血管终点发生的病因学因素的认识将为干预措施的开发和测试提供信息，以减少晚期肾衰竭和心血管发病率和死亡率的负担。 公共卫生相关性：慢性肾脏疾病在许多人中进展，需要透析。这些患者中的许多人也患有心脏病。治疗血压减轻了一些，但不是所有的这些影响，尽管良好的血压控制。由于高血压的靶器官（肾脏，心脏，大脑）是由循环联系在一起的，该项目评估了循环的特定方面，这可能是疾病进展的重要方面。

DESCRIPTION (provided by applicant): The National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) established the Chronic Renal Insufficiency Cohort Study in 2001. The principal goals of the CRIC Study are to examine risk factors for chronic kidney disease (CKD) progression (i.e. further loss of kidney function) and cardiovascular events among patients with varying severity of CKD, and develop predictive models that will identify high-risk subgroups with CKD. The latter results will target enrollment of high-risk subjects into future treatment trials and increase application of available preventive therapies. Hypertension treatment has been an effective intervention altering the course of renal function loss in CKD. However, the recent findings of the African American Study of Kidney disease suggest that kidney function loss and cardiovascular events occur despite excellent blood pressure control on regimens that block the renin- angiotensin system. This raises the possibility that interventions that go beyond blood pressure reduction are necessary to halt the progression of CKD and prevent incident cardiovascular disease (CVD). Available data suggest that large artery stiffness plays a role in both kidney dysfunction and CVD. Determination of aortic pulse wave velocity (PWV; the gold standard measure of large artery stiffness) and central pulse pressure are novel methodologies that have provided useful information in cardiovascular disease epidemiology. We propose to use these methods to study both CVD as well as progressive kidney function loss in the already recruited CRIC population anticipating that this will contribute to narrowing the knowledge gap between vascular function and kidney/cardiovascular outcomes. We hypothesize that aortic pulse wave velocity predicts kidney and CVD outcomes in subjects with CKD. We propose to test this hypothesis with three specific aims: Specific Aim 1: To determine pulse wave velocity in a heterogeneous cohort of subjects with chronic kidney disease. Specific Aim 2: To determine the utility of pulse wave velocity to predict of renal failure progression in a CKD cohort. Specific Aim 3: To determine the utility of pulse wave velocity to predict cardiovascular outcomes in a CKD cohort. These aims will be carried out in a population of 3000 individuals, 50% with diabetes, recruited at clinical centers in the USA beginning in 2003. All data derived from this study are managed at the University of Pennsylvania by the Science Data Coordinating Center (SDCC). The techniques employed involve minimal risk to subjects and a modest burden of time to perform. Kidney function and CVD are carefully measured pre-specified endpoints in CRIC. Improved recognition of etiological factors in CKD progression and cardiovascular endpoint occurrence will inform the development and testing of interventions to reduce the burden of advanced kidney failure and cardiovascular morbidity and mortality. PUBLIC HEALTH RELEVANCE: Chronic kidney disease progresses in many people making dialysis necessary. Many of these patients also have heart disease. Treating blood pressure mitigates some but not all of these effects, despite good blood pressure control. Since the target organs of hypertension (kidney,heart,brain) are linked by the circulation this project evaluates specific aspects of the circulation which may be important in disease progression.