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）是老年人的一个重要健康问题，肾衰竭的发病率不断增加，早期CKD的患病率很高，结果很差，费用很高。众所周知，随着年龄的增长，GFR下降，白蛋白尿增加，并且两者都与肾衰竭，CKD和心血管疾病（CVD）并发症的风险增加相关。然而，与年龄相关的肾功能变化的原因尚不清楚，在很大程度上是由于缺乏关于代表性老年人群GFR水平的可靠信息。我们的中心假设是，老年人GFR降低和白蛋白尿增加反映了由于在整个生命过程中暴露于CVD危险因素导致的肾脏微血管疾病，部分由主动脉僵硬度增加介导。年龄、基因/环境易感性-雷克雅未克研究（AGES-Reykjavik Study）（N 01-AG-1-2100）是一项遗传流行病学研究，嵌套在1967年开始的冰岛CVD人群队列研究中。冰岛的心血管疾病负担与美国高加索人群相似。该研究包括对中年CVD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。我们建议对这次访问进行辅助研究。具体目标包括：1.通过年龄、性别和CVD危险因素确定测量的GFR水平。我们将在一个子队列（N=800）中使用碘海醇的血浆清除率测量GFR。2.确定CKD在衰老中的负担。我们将测定所有受试者（N=3484）的肌酐、胱抑素C和白蛋白尿，将其与CKD并发症、临床和亚临床CVD和CVD风险因素联系起来，并将结果与可比的美国人群进行比较（NHANES 99-04）。3.将晚年肾功能与中年和晚年CVD危险因素和晚年主动脉僵硬度联系起来。在前一次访视时获得了940例受试者的主动脉僵硬度测量值，并将在本次访视时获得所有受试者的主动脉僵硬度测量值（N=3484）。在社区居住老年人的代表性队列中测量GFR和主动脉僵硬度将允许最准确地调查肾功能水平、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发展的可改变风险因素以及制定针对性策略预防和治疗老年人CKD至关重要。首席研究员和研究团队非常适合进行这项调查。他们的专业知识，加上AGES-Reykjavik研究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严格的检查。 项目叙述：慢性肾脏疾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，被认为与随着年龄的增长而发生的主动脉硬化引起的高血压有关。本研究将测量一组社区居住的老年人的肾功能和主动脉硬化。