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）： 慢性肾脏疾病（CKD）是老年人的重要健康问题，肾功能衰竭的发生率越来越高，CKD早期阶段的患病率越来越高，结果较差，成本较高。众所周知，GFR的下降和蛋白尿随老化而增加，并且都独立并结合起来，肾衰竭，CKD并发症的风险增加，CKD和心血管疾病（CVD）的风险增加。但是，由于没有关于代表性老年人群GFR水平的可靠信息，在很大程度上尚未很好地理解与年龄相关的肾功能变化的原因。我们的中心假设是，由于在整个生命过程中暴露于CVD危险因素，老年人的GFR降低和增加的蛋白尿反映了肾脏中的微血管疾病，部分原因是主动脉僵硬。年龄，基因/环境易感性 - 雷卡维奇研究（年龄 - 雷克雅未克研究）（N01-AG-1-2100）是一项遗传流行病学研究，该研究嵌套在1967年始于冰岛的基于人群的CVD中。该研究包括对中年中CVD风险因素的全面评估；后期定量特征的血管，神经认知，肌肉骨骼和代谢表型；和基因组广泛的扫描。我们向当前的访问提出了一项辅助研究。具体目的包括：1。确定按年龄，性别和CVD风险因素确定测得的GFR的水平。我们将使用亚果醇中的Iohexol的血浆清除率（n = 800）测量GFR。 2。确定CKD在衰老中的负担。我们将在所有受试者中分析肌酐，胱抑素C和蛋白尿（n = 3484），将它们与CKD并发症，临床和亚临床CVD和CVD风险因素相关联，并将结果与​​可比的美国人群进行比较（NHANES 99-04）。 3。将后期肾脏功能与中年和晚期CVD危险因素和晚期主动脉僵硬联系起来。在上一次访问时，在940名受试者中获得了主动脉僵硬度的度量，并将在当前访问时在所有受试者中获得（n = 3484）。在代表性的居住老年人的代表人群中，GFR和主动脉僵硬度的测量将允许对肾功能水平，CKD负担以及随着年龄的年龄的下降肾脏功能下降的潜在机制进行最准确的研究。该信息对于确定CKD发展的可修改风险因素以及针对老年CKD的预防和治疗的有针对性策略至关重要。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，以及在年龄重生研究中的独特设计和全面评估，将允许对肾脏功能，主动脉僵硬和衰老之间的关系进行最全面和严格的研究。 项目叙述：慢性肾脏疾病是老年人的常见问题，与肾衰竭的风险增加，肾功能低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，但原因尚未完全理解，被认为与衰老随着主动脉的僵硬引起的高血压有关。这项研究将在一组居住的老年人中测量肾功能和主动脉的僵硬。