Kidney Function, Aortic Stiffness and Aging

肾功能、主动脉僵硬和衰老

• 批准号: 8110885
• 负责人: ANDREW S LEVEY
• 金额: $ 30.9万
• 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: 2010-09-30 至 2012-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110885
• 关键词: Age; Aging; Albumins; Albuminuria; Ancillary Study; Aorta; Applications Grants; Arts; Biological Assay; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Caucasians; Caucasoid Race; Chronic Disease; Chronic Kidney Failure; Clinical; Cohort Studies; Communities; Creatinine; Data; Data Element; Developed Countries; Development; Diabetic Angiopathies; Disease; Elderly; Enrollment; Environment; Evaluation; Exposure to; Genes; Glomerular Filtration Rate; Health; Heart Diseases; 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; Population Study; Predisposition; Prevention strategy; Principal Investigator; Recording of previous events; Renal function; Research; Risk; Risk Factors; Role; Sampling; Spottings; Staging; 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; urinary

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）是老年人的重要健康问题，肾衰竭的发病率不断增加，CKD早期患病率很高，预后差且费用高。众所周知，随着年龄的增长，肾小球滤过率 (GFR) 下降，蛋白尿增加，两者单独或共同增加肾衰竭、CKD 并发症和心血管疾病 (CVD) 的风险。然而，与年龄相关的肾功能变化的原因尚不清楚，很大程度上是由于缺乏有关代表性老年人群 GFR 水平的可靠信息。我们的中心假设是，老年人的肾小球滤过率降低和蛋白尿增加反映了由于在整个生命过程中暴露于CVD危险因素而导致的肾脏微血管疾病，部分是由主动脉僵硬度增加介导的。年龄、基因/环境易感性-雷克雅未克研究（AGES-Reykjavik 研究）(N01-AG-1-2100) 是一项遗传流行病学研究，源于 1967 年在冰岛开始的基于人群的 CVD 队列研究。冰岛的 CVD 负担与美国白种人群体相似。该研究包括对中年CVD危险因素的全面评估；晚年数量性状的血管、神经认知、肌肉骨骼和代谢表型；和全基因组扫描。我们建议对本次访问进行一项辅助研究。具体目标包括： 1. 根据年龄、性别和 CVD 危险因素确定测量的 GFR 水平。我们将使用亚组 (N=800) 中碘海醇的血浆清除率来测量 GFR。 2.确定CKD对衰老的负担。我们将检测所有受试者 (N=3484) 的肌酐、半胱氨酸蛋白酶抑制剂 C 和蛋白尿，将其与 CKD 并发症、临床和亚临床 CVD 以及 CVD 危险因素联系起来，并将结果与​​可比较的美国人群 (NHANES 99-04) 进行比较。 3. 将晚年肾功能与中年和晚年 CVD 危险因素以及晚年主动脉僵硬度联系起来。在上次就诊时对 940 名受试者进行了主动脉僵硬度测量，并将在本次就诊时对所有受试者进行测量 (N=3484)。对社区居住老年人的代表性队列中的 GFR 和主动脉硬度进行测量，将有助于最准确地研究肾功能水平、CKD 负担以及肾功能随年龄下降的潜在机制。这些信息对于识别 CKD 发展的可改变危险因素以及制定预防和治疗老年人 CKD 的有针对性的策略至关重要。主要研究者和研究团队非常适合开展这项调查。他们的专业知识，加上 AGES-雷克雅未克研究的独特设计和全面评估，将能够对肾功能、主动脉僵硬度和衰老之间的关系进行最全面和严格的检查。 项目叙述：慢性肾脏病是老年人的常见问题，与肾衰竭、肾功能低下并发症以及心脏和血管疾病的风险增加有关。肾功能随着年龄的增长而下降，但其原因尚不完全清楚，被认为与随着年龄增长而出现的主动脉硬化引起的高血压有关。这项研究将测量一组社区居住老年人的肾功能和主动脉硬化情况。