Pulse wave velocity in chronic kidney disease

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。高血压治疗是改变CKD肾功能损害过程的最有效的干预措施。然而，用于治疗高血压的药物对肾功能的益处不同。这增加了这样一种可能性，即降压本身只能部分解释它们的有益效果，并促使人们更广泛地理解血管对疾病的适应，如慢性肾脏病。脉搏波速度(PWV)的测定反映了大血管硬度，在心血管疾病流行病学中提供了有用的信息。 我们假设脉搏波速度可以预测慢性肾脏疾病患者的进展，我们建议用三个具体的目标进行测试： 具体目标1：确定慢性肾脏疾病患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。 这些目标将在美国7个临床中心招募的3000人中实现，其中50%患有糖尿病，从2003年开始，历时30个月。来自这项研究的所有数据将在宾夕法尼亚大学与生物统计和流行病学中心合作管理。所采用的技术不会对受试者造成风险，执行的时间负担也最小。这份修订的申请提供了关于技术重复性的数据、扩展的初步数据、中央增强指数措施的合并以及修订的分析和权力部分，这些部分解决了第一次审查中的批评提出的许多重要问题。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允许开发和测试干预措施，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。

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 the most effective intervention altering the course of renal function loss in CKD. However, the drugs used in the treatment of hypertension differ in their benefits on renal function. This raises the possibility that blood pressure reduction by itself only partly explains their beneficial effect and beckons a broader understanding of vascular adaptation to diseases such as CKD. Determination of the pulse wave velocity (PWV) a reflection of large vessel stiffness has provided useful information in cardiovascular disease epidemiology. We hypothesize that pulse wave velocity predicts progression in subjects with chronic kidney disease, which we propose to test 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 7 clinical centers in the USA recruited over 30 months beginning in 2003. All data derived from this study will be managed here at Penn in cooperation with the Center for Biostatistics and Epidemiology. The techniques employed involve no risk to subjects and a minimal burden of time to perform. This revised application presents data on technique reproducibility, expanded preliminary data, tile incorporation of central augmentation index measures, and revised analysis & power sections that address tile many important issues raised by the critiques from tile first review. Improved recognition of etiological factors in CKD progression and cardiovascular endpoint occurrence will permit development and testing of interventions to reduce the burden of advanced renal failure and cardiovascular morbidity and mortality.