Novel Cardiac Risk Factors & Endothelial Function in CKD

新的心脏危险因素

• 批准号: 7459099
• 负责人: Vandana Menon
• 金额: $ 15.7万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459099
• 关键词: Adipocytes; Advanced Glycosylation End Products; Affect; American; Arteries; Autosomal Dominant Polycystic Kidney; Award; Biological Markers; Blood Vessels; C-reactive protein; Cardiac; Cardiovascular Diseases; Chronic Kidney Failure; Cohort Studies; Coronary Arteriosclerosis; Data; Development; Diabetes Mellitus; Diabetic Nephropathy; Dialysis procedure; Diet Modification; Dietary Proteins; Disease Outcome; Elevation; Etiology; Freezing; Functional disorder; General Population; Glutathione Disulfide; Goals; Hereditary Disease; High Prevalence; Human; Hyperlipidemia; Hypertension; Impairment; In Vitro; Inflammation; Institutes; Insulin; Insulin Resistance; Interleukin-6; Intervention; Investigation; Isoprostanes; Kidney Diseases; Kidney Failure; Lead; Life; Lysine; Malnutrition; Measures; Mediating; Mentors; Modeling; Morbidity - disease rate; Nitric Oxide Synthase; Outcome; Oxidative Stress; Participant; Pathology; Pathway interactions; Patients; Peripheral; Physical Dialysis; Play; Polycystic Kidney Diseases; Population; Premature Mortality; Prevention; Prevention strategy; Principal Investigator; Public Health; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Range; Rate; Rattus; Reduced Glutathione; Research Design; Research Personnel; Resistance; Resources; Risk; Risk Factors; Role; Sampling; Staging; Testing; Time; Training; adiponectin; attributable mortality; blood pressure regulation; brachial artery; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; career; cohort; follow-up; inhibitor/antagonist; mortality; non-diabetic; novel; prevent; prospective; therapeutic target; tonometry

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of morbidity and mortality among patients with chronic kidney disease. This excess risk is only partly attributable to a high prevalence of traditional cardiovascular risk factors. The principal investigator's goal is to establish a career as an independent investigator with the broad objectives of understanding of the pathophysiologic mechanisms leading to cardiovascular disease and developing effective preventive strategies to reduce the burden of cardiovascular disease in kidney disease. The proposed study will investigate the mechanisms underlying development of cardiovascular disease in the earlier stages of non-diabetic chronic kidney disease utilizing data from two National Institutes of Diabetes & Digestive & Kidney Diseases (NIDDK) sponsored trials. The overall hypothesis is that: Non-diabetic chronic kidney disease is characterized by early elevation of markers of inflammation, oxidative stress and insulin resistance, and that these risk factors are associated with cardiovascular disease in this patient population. The Modification of Diet in Renal Disease (MDRD) Study was a large randomized controlled trial of patients in the earlier stages of chronic kidney disease. Participants in the MDRD Study had predominantly non-diabetic kidney disease of varying etiologies. The Halt Progression of Polycystic Kidney Disease trial is a randomized trial to slow the progression of kidney disease in patients with autosomal dominant polycystic kidney disease (ADPKD). These two patient populations provide a unique opportunity to examine the relationship between kidney disease and novel cardiac risk factors, and to study the role of these novel risk factors in the pathophysiology of cardiovascular disease, in the absence of important confounders such as diabetes, dialysis and malnutrition. The study hypothesis will be tested using three specific aims: 1. To determine whether inflammation, oxidative stress, insulin resistance, and endothelial dysfunction in the earlier stages of chronic kidney disease are associated with cardiovascular disease. 2. To determine whether ADPKD is associated with inflammation, insulin resistance, and oxidative stress 3. To determine whether inflammation, insulin resistance, and oxidative stress are associated with endothelial dysfunction, measured as brachial artery reactivity and peripheral artery tonometry, in ADPKD. The novel risk factors under investigation in this proposal could serve to identify high-risk patients for targeted interventions to prevent or delay the adverse outcomes associated with cardiovascular disease. The applicant has chosen a group of distinguished mentors and collaborators to support this project. This award will provide Dr. Menon with the final training necessary for her to make the transition from trainee to principal investigator.

描述（由申请人提供）： 心血管疾病是慢性肾病患者发病和死亡的主要原因。这种过度风险只是部分归因于传统心血管风险因素的高患病率。主要研究者的目标是建立作为独立研究者的职业生涯，其广泛目标是了解导致心血管疾病的病理生理机制，并制定有效的预防策略，以减少肾脏疾病中心血管疾病的负担。这项拟议的研究将利用来自两个国立糖尿病、消化和肾脏疾病研究所（NIDDK）赞助的试验的数据，研究非糖尿病慢性肾脏疾病早期阶段心血管疾病发展的潜在机制。总体假设是：非糖尿病慢性肾脏疾病的特征是炎症、氧化应激和胰岛素抵抗标志物的早期升高，并且这些风险因素与该患者人群中的心血管疾病相关。 肾脏疾病饮食改良（MDRD）研究是一项针对早期慢性肾脏疾病患者的大型随机对照试验。MDRD研究的参与者主要患有各种病因的非糖尿病肾病。停止多囊肾病进展试验是一项旨在减缓常染色体显性遗传性多囊肾病（ADPKD）患者肾脏疾病进展的随机试验。这两个患者人群提供了一个独特的机会来检查肾脏疾病和新的心脏风险因素之间的关系，并研究这些新的风险因素在心血管疾病的病理生理学中的作用，在没有重要的混杂因素，如糖尿病，透析和营养不良。 研究假设将使用三个具体目标进行测试：1。确定慢性肾脏疾病早期阶段的炎症、氧化应激、胰岛素抵抗和内皮功能障碍是否与心血管疾病相关。2.确定ADPKD是否与炎症、胰岛素抵抗和氧化应激有关3.确定ADPKD患者的炎症、胰岛素抵抗和氧化应激是否与肱动脉反应性和外周动脉张力测定法测定的内皮功能障碍相关。 本提案中正在研究的新风险因素可用于识别高危患者，以进行有针对性的干预，预防或延迟与心血管疾病相关的不良结局。申请人已选择了一批杰出的导师和合作者来支持这个项目。该奖项将为梅农博士提供必要的最后培训，使她从实习生过渡到主要研究者。