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)进展的风险因素(即肾功能的进一步丧失)和不同严重程度的CKD患者的心血管事件，并开发预测模型，以确定CKD的高危亚组。后一项结果将把高危受试者纳入未来的治疗试验，并增加现有预防疗法的应用。高血压治疗已成为改变慢性肾脏病肾功能损害过程的有效干预手段。然而，非裔美国人肾脏疾病研究最近的发现表明，尽管对阻断肾素-血管紧张素系统的治疗方案进行了良好的血压控制，但肾功能丧失和心血管事件仍会发生。这增加了这样一种可能性，即为了阻止CKD的进展和预防心血管疾病(CVD)，除了降压之外的干预措施是必要的。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着作用。主动脉脉搏波速度(PWV；大动脉硬度的黄金标准)和中心脉压的测定是在心血管疾病流行病学中提供有用信息的新方法。我们建议使用这些方法来研究已经招募的CRIC人群中的心血管疾病和进行性肾功能丧失，预期这将有助于缩小血管功能和肾脏/心血管结果之间的知识差距。我们假设，在CKD受试者中，主动脉脉搏波速度可以预测肾脏和心血管疾病的预后。我们建议用三个具体目标来检验这一假说：具体目标1：确定慢性肾脏疾病受试者的不同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有效性。具体目标3：确定脉搏波速度在CKD队列中预测心血管结局的实用性。从2003年开始，这些目标将在美国临床中心招募的3000人中实现，其中50%患有糖尿病。来自这项研究的所有数据都由宾夕法尼亚大学的科学数据协调中心(SDCC)管理。所采用的技术涉及到对受试者最小的风险和适度的时间负担。肾功能和心血管疾病是CRIC中预先指定的终点仔细测量的。对慢性肾脏病进展和心血管终点发生的病因认识的提高将为开发和测试干预措施提供信息，以减少晚期肾功能衰竭的负担以及心血管发病率和死亡率。 公共卫生相关性：慢性肾脏疾病在许多人中进展，因此有必要进行透析。这些患者中的许多人还患有心脏病。尽管血压控制得很好，但治疗血压可以缓解部分但不是所有这些影响。由于高血压的靶器官(肾、心、脑)通过循环联系在一起，这个项目评估了循环的特定方面，这些方面可能在疾病进展中很重要。

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.