Kidney Function, Aortic Stiffness and Aging

肾功能、主动脉僵硬和衰老

• 批准号: 8066727
• 负责人: ANDREW S LEVEY
• 金额: $ 45.63万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066727
• 关键词: Age; Aging; Albumins; Albuminuria; Ancillary Study; Aorta; Biological Assay; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Caucasians; Caucasoid Race; Chronic Disease; Chronic Kidney Failure; Clinical; Cohort Studies; Communities; Creatinine; Data; Developed Countries; Development; Diabetic Angiopathies; Disease; Elderly; Enrollment; Environment; Evaluation; Exposure to; Health; Heart; High Prevalence; Hypertension; Iceland; Incidence; Individual; Investigation; Iohexol; Kidney; Kidney Diseases; Kidney Failure; Life Cycle Stages; Longevity; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Metabolic; Microcirculation; Musculoskeletal; National Health and Nutrition Examination Survey; Neurocognitive; Organ; Outcome; Pathway interactions; Phenotype; Plasma; Population; Predisposition; Prevention strategy; Principal Investigator; Recording of previous events; Renal function; Research; Risk; Risk Factors; Role; Sampling; Spottings; Staging; United States National Institutes of Health; Urine; Visit; age related; aging gene; arterial tonometry; cardiovascular disorder risk; cardiovascular risk factor; cohort; cost; design; disability; electric impedance; epidemiology study; genetic epidemiology; genome wide association study; interest; middle age; modifiable risk; population based; post gamma-globulins; pressure; prevent; prospective; sex; tonometry; trait

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is an important health problem in the elderly, with an increasing incidence of kidney failure and a high prevalence of earlier stages of CKD, with poor outcomes and high cost. It is well known that GFR declines and albuminuria increases with aging, and that both are associated, independently and in combination, with an increased risk for kidney failure, complications of CKD and cardiovascular disease (CVD). However, the causes of age-related changes in kidney function are not well understood, in large part, due to absence of reliable information about the level of GFR in a representative elderly population. Our central hypothesis is that decreased GFR and increased albuminuria in the elderly reflect microvascular disease in the kidney due to exposure to CVD risk factors throughout the life course, mediated in part by increased aortic stiffness. The Age, Gene/Environment Susceptibility-Reykjavic Study (AGES-Reykjavik Study) (N01-AG-1-2100) is a genetic epidemiology study nested in a population based cohort study of CVD in Iceland begun in 1967. Iceland has a burden of CVD similar to the US Caucasian population. The study includes a comprehensive assessment of CVD risk factors in mid-life; vascular, neurocognitive, musckoskeletal and metabolic phenotypes of quantitative traits in late life; and a genome wide scan. We propose an ancillary study to the current visit. Specific aims include: 1. To determine the level of measured GFR by age, sex and CVD risk factors. We will measure GFR using plasma clearance of iohexol in a subcohort (N=800). 2. To determine the burden of CKD in aging. We will assay creatinine, cystatin C and albuminuria in all subjects (N=3484), relate them to CKD complications, clinical and subclinical CVD and CVD risk factors and compare the results to a comparable US population (NHANES 99-04). 3. To relate late-life kidney function to midlife and late-life CVD risk factors and late-life aortic stiffness. Measures of aortic stiffness were obtained in 940 subjects at the previous visit and will be obtained in all subjects at the current visit (N=3484). Measurement of GFR and aortic stiffness in a representative cohort of community dwelling elderly individuals will allow the most accurate investigation of the level of kidney function, burden of CKD, and potential mechanisms for the decline in kidney function with age. This information is essential for the identification of modifiable risk factors for development of CKD, as well as development of targeted strategies for prevention and treatment of CKD in the elderly. The principal investigator and research team are ideally suited to carry out this investigation. Their expertise, together with the unique design and comprehensive assessment in the AGES-Reykjavik Study, will allow for the most comprehensive and rigorous examination of relationships among kidney function, aortic stiffness and aging. Project Narrative: Chronic kidney disease is a common problem in the elderly that is associated with an increased risk for kidney failure, complications of low kidney function and disease of the heart and blood vessels. Kidney function goes down with age but the cause is not completely understood and is thought to be related to high blood pressure caused by stiffening of the aorta that occurs with aging. This study will measure kidney function and stiffening of the aorta in a group of community dwelling older adults.

描述(由申请人提供)： 慢性肾脏病(CKD)是老年人的一个重要健康问题，肾功能衰竭的发生率越来越高，早期CKD的患病率高，预后差，费用高。众所周知，随着年龄的增长，肾小球滤过率下降和蛋白尿增加，并且两者独立或联合与肾衰竭、慢性肾脏病并发症和心血管疾病(CVD)的风险增加相关。然而，与年龄相关的肾功能改变的原因尚不清楚，这在很大程度上是由于缺乏关于具有代表性的老年人口中GFR水平的可靠信息。我们的中心假设是，老年人GFR减少和蛋白尿增加反映了由于在整个生命过程中暴露于心血管危险因素而导致的肾脏微血管疾病，部分原因是主动脉僵硬增加。年龄、基因/环境易感性-雷克雅未克研究(AGES-雷克雅未克研究)(N01-AG-1-2100)是一项遗传流行病学研究，嵌套在冰岛始于1967年的基于人群的心血管疾病队列研究中。冰岛的心血管疾病负担与美国的高加索人口相似。这项研究包括对中年心血管疾病风险因素的全面评估；晚年数量性状的血管、神经认知、肌肉骨骼和代谢表型；以及全基因组扫描。我们建议对此次访问进行一项辅助研究。具体目标包括：1.确定按年龄、性别和心血管危险因素测量的GFR水平。我们将使用亚队列(N=800)中的碘海醇血浆清除率来测量GFR。2.确定CKD在衰老过程中的负担。我们将检测所有受试者的肌酐、胱抑素C和蛋白尿(N=3484)，将它们与CKD并发症、临床和亚临床心血管疾病以及心血管疾病危险因素相关联，并将结果与美国可比人群(NHANES 99-04)进行比较。3.探讨老年肾功能与中老年心血管疾病危险因素及老年主动脉僵硬的关系。940名受试者在前一次就诊时测量了主动脉硬度，本次就诊时所有受试者都将获得(N=3484)。对社区老年人的代表性队列中GFR和主动脉硬度的测量将有助于最准确地调查肾功能水平、慢性肾脏病的负担以及肾功能随年龄下降的潜在机制。这些信息对于确定慢性肾脏病发生的可改变的危险因素，以及制定有针对性的预防和治疗老年人慢性肾脏病的策略是至关重要的。首席调查员和研究团队非常适合开展这项调查。他们的专业知识，加上在AGES-雷克雅未克研究中的独特设计和全面评估，将允许对肾功能、主动脉僵硬和衰老之间的关系进行最全面和最严格的检查。 项目简介：慢性肾脏疾病是老年人的常见问题，与肾衰竭风险增加、肾功能低下的并发症以及心脏和血管疾病有关。肾功能会随着年龄的增长而下降，但其原因尚不完全清楚，并被认为与随着年龄增长而出现的主动脉僵硬引起的高血压有关。这项研究将测量一组居住在社区的老年人的肾功能和主动脉硬化。