CRIC Ancillary Study: Carbamylated low-density lipoprotein and cardiovascular eve

CRIC辅助研究：氨甲酰化低密度脂蛋白与心血管疾病

• 批准号: 8125105
• 负责人: Sudhir V Shah
• 金额: $ 38万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125105
• 关键词: Address; Adhesions; Adopted; Age; Ancillary Study; Animal Model; Animals; Ankle; Antibodies; Area; Arteriosclerosis; Atherosclerosis; Basic Science; Biological; Biological Assay; Biological Factors; Biological Markers; Blood Urea Nitrogen; Blood specimen; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Cessation of life; Characteristics; Cholesterol; Chronic; Chronic Disease; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Cohort Studies; Complex; Consumption; Coronary artery; Data; Data Analyses; Data Collection; Data Coordinating Center; Databases; Development; Diabetes Mellitus; Discrimination; Disease; Disease Outcome; Disease Progression; Doctor of Philosophy; End stage renal failure; Endothelial Cells; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemiologist; Ethnic Origin; Evaluation; Event; Functional disorder; Funding; Gender; Glomerular Filtration Rate; Goals; Grant; Guidelines; Heart Diseases; Human; Hypertension; In Vitro; Incidence; Individual; Injury; Investments; Joints; Kidney; Kidney Diseases; Kidney Failure; Laboratories; Letters; Lipoprotein (a); Low-Density Lipoproteins; Measures; Methods; Modality; Modeling; Morbidity - disease rate; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Notification; Obesity; Observational Study; Parents; Participant; Pathologist; Patients; Placebo Control; Plasma; Population; Population Heterogeneity; Preventive; Process; Proteins; Proteinuria; Protocols documentation; Published Comment; Publishing; ROC Curve; Race; Recurrence; Renal function; Research Design; Research Personnel; Risk; Risk Factors; Sample Size; Sampling; Serum; Smooth Muscle; Solid; Stratification; Thick; United States National Institutes of Health; Urea; Variant; Vascular Diseases; Work; Yang; base; cardiovascular disorder risk; cohort; complement C4d; coronary artery calcification; design; experience; high risk; indexing; insight; intima media; low density lipoprotein inhibitor; meetings; member; monocyte; mortality; novel; novel strategies; post gamma-globulins; prognostic; public health relevance; response

DESCRIPTION (provided by applicant): The present proposal investigates the utility of a nontraditional risk factor, serum cLDL, as a risk factor associated with cardiac events and arteriosclerosis in patients with CKD utilizing the wealth of information from the CRIC Study. This proposal has been approved by the CRIC Ancillary Steering Committee and will include approximately 3,600 CRIC participants with mild to moderate renal disease who have been followed for up to five years or until death. Blood urea dissociates to form cyanate that may alter proteins including low-density lipoprotein (LDL) by a process known as carbamylation. Our recent studies demonstrate that cLDL has all of the biological effects relevant to atherosclerosis. In addition, we have demonstrated the development of aortic atherosclerosis in mice that have elevated plasma cLDL due either to chronic kidney failure or chronic urea consumption. Finally, in human studies, end-stage kidney disease (ESKD) patients have significantly elevated plasma cLDL concentration. Our hypothesis is that cLDL is associated with prevalent, recurrent, and incident cardiovascular disease and with measures of arteriosclerosis (carotid intima-media thickness [IMT] and coronary artery calcification [CAC]) in patients with CKD. A secondary objective is to determine the relationship between serum cLDL and serum urea and/or level of renal function (estimated glomerular filtration rate [eGFR]). We have raised the antibody to measure cLDL and have developed a sensitive and specific cLDL sandwich ELISA assay. This ancillary study will cause no burden on participating patients and will examine a potentially important non-traditional atherosclerotic risk factor in patients with CKD. This proposal is timely because the cardiovascular events in patients who have been enrolled during 2003-2007 are currently being evaluated and the data will be available by 2010. PUBLIC HEALTH RELEVANCE: Patients with kidney disease have a high risk of developing heart disease. Traditional risk factors for heart disease like high cholesterol do not explain this risk. Patients with kidney disease have higher levels of blood urea nitrogen, which can be transformed into products that modify proteins by a process known as carbamylation. The overall goal of this proposal is to utilize the wealth of information that has been gathered as part of the NIH-funded Chronic Renal Insufficiency Cohort (CRIC) Study to evaluate the relevance of carbamylated LDL (cLDL), a nontraditional CV risk factor, to cardiovascular disease in patients with chronic kidney disease.

描述（由申请人提供）： 本提案调查了非传统危险因素血清CLDL的实用性，它是CKD患者的心脏事件和动脉硬化相关的危险因素，利用CRIC研究中的大量信息。该提案已获得CRIC辅助指导委员会的批准，将包括大约3,600名CRIC参与者患有轻度至中度肾脏疾病的参与者，这些参与者已遵循长达五年或直到死亡。血尿素解离形成氰酸盐，可能通过称为氨基甲基化的过程改变蛋白质，包括低密度脂蛋白（LDL）。我们最近的研究表明，CLDL具有与动脉粥样硬化有关的所有生物学作用。此外，我们已经证明了由于慢性肾衰竭或慢性尿素消耗而导致血浆CLDL升高的小鼠主动脉粥样硬化的发展。最后，在人类研究中，末期肾脏疾病（ESKD）患者的血浆CLDL浓度显着升高。我们的假设是，CLDL与CKD患者的患者（Carotid intima-Media厚度[IMT]和冠状动脉钙化[CAC]）有关，与普遍，复发和入射心血管疾病以及动脉粥样硬化的量度有关。次要目标是确定血清CLDL与血清尿素与/或肾功能水平（估计的肾小球滤过率[EGFR]）之间的关系。我们已经提出了测量CLDL的抗体，并开发了一种敏感且特异的CLDL三明治ELISA分析。这项辅助研究将不会对参加患者造成负担，并将检查CKD患者中潜在的重要非传统动脉粥样硬化危险因素。该建议之所以及时，是因为目前正在评估2003- 2007年招募的患者的心血管事件，并且数据将于2010年提供。 公共卫生相关性： 肾脏疾病患者患心脏病的风险很高。高胆固醇等心脏病的传统危险因素不能解释这种风险。肾脏疾病患者的血尿素氮水平较高，可以通过称为氨基甲基化的过程转化为修饰蛋白质的产物。该提案的总体目的是利用已收集的信息作为NIH资助的慢性肾脏不足同类群（CRIC）研究的一部分，以评估甲基化LDL（CLDL）的相关性，这是一种非传统CV风险因素，与慢性儿童疾病患者的心血管疾病。