Kidney Function, Aortic Stiffness and Aging

慢性肾脏病（CKD）是老年人的一个重要健康问题， 肾衰竭和早期CKD的高患病率，结果差，费用高。众所周知 随着年龄的增长，GFR下降，白蛋白尿增加，两者独立相关， 合并使用时，肾衰竭、CKD并发症和心血管疾病的风险增加 （CVD）。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， 部分原因是缺乏关于代表性老年人群GFR水平的可靠信息。我们 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风险因素而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研究）（N 01-AG-1-2100）是一项 遗传流行病学研究嵌套在人群为基础的队列研究心血管疾病在冰岛开始于1967年。 冰岛的心血管疾病负担与美国高加索人群相似。该研究包括一个全面的 中年CVD风险因素评估;血管、神经认知、肌肉骨骼和代谢 晚年数量性状的表型;以及全基因组扫描。我们建议进行辅助研究， 这次访问。具体目标包括：1.根据年龄、性别和CVD风险确定测量的GFR水平 因素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.以确定 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， 将它们与CKD并发症、临床和亚临床CVD以及CVD危险因素联系起来，并比较结果 与美国人口相当（NHANES 99-04）。3.将晚年肾功能与中年和晚年联系起来 心血管疾病危险因素和晚年主动脉僵硬。在940名受试者中获得了主动脉僵硬度的测量结果， 将在所有受试者（N=3484）的当前访视中获得。 社区老年人代表性队列GFR和主动脉僵硬度的测量 个体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 确定CKD发展的可改变风险因素，以及制定有针对性的策略 用于预防和治疗老年人的CKD。首席研究员和研究团队理想地 适合进行这次调查他们的专业知识，加上独特的设计和全面的 AGES-Reykjavik研究中的评估，将允许最全面和严格的检查， 肾功能、主动脉僵硬度和衰老之间的关系。

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.