Pulse wave velocity in chronic kidney diseases

描述（由申请人提供）：美国国家糖尿病、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研究的主要目标是在不同严重程度的CKD患者中检查慢性肾脏疾病（CKD）进展（即进一步肾功能丧失）和心血管事件的危险因素，并建立预测模型，以确定CKD的高危亚组。后者的结果将针对高风险受试者纳入未来的治疗试验，并增加现有预防疗法的应用。高血压治疗是改变慢性肾病肾功能丧失过程的有效干预措施。然而，非裔美国人肾脏疾病研究的最新发现表明，尽管阻断肾素-血管紧张素系统的治疗方案能很好地控制血压，但肾功能丧失和心血管事件仍会发生。这增加了一种可能性，即除了降低血压之外的干预措施对于阻止CKD的进展和预防心血管疾病（CVD）的发生是必要的。现有数据表明，大动脉僵硬在肾功能障碍和心血管疾病中都起作用。测定主动脉脉波速度（PWV，大动脉硬度的金标准）和中心脉压是一种新颖的方法，为心血管疾病流行病学提供了有用的信息。我们建议在已经招募的CRIC人群中使用这些方法来研究CVD和进行性肾功能丧失，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。我们假设主动脉脉波速度可以预测CKD患者肾脏和心血管疾病的预后。我们提出有三个特定目的来验证这一假设：特定目的1：确定慢性肾脏疾病患者异质队列中的脉搏波速度。具体目的2：确定脉搏波速度在CKD队列中预测肾功能衰竭进展的效用。具体目的3：确定脉搏波速度在CKD队列中预测心血管结局的效用。这些目标将在3000个人中进行，其中50%患有糖尿病，从2003年开始在美国的临床中心招募。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。所采用的技术对受试者的风险最小，执行时间负担适中。在CRIC中，肾功能和CVD是预先指定的终点。提高对CKD进展和心血管终点发生的病因因素的认识，将为开发和测试干预措施提供信息，以减少晚期肾衰竭和心血管发病率和死亡率的负担。

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.