Kidney Function, Aortic Stiffness and Aging

慢性肾脏病(CKD)是老年人的重要健康问题，其发病率呈上升趋势。 肾功能衰竭和早期CKD的高患病率，预后差，费用高。这是众所周知的 随着年龄的增长，肾小球滤过率下降，蛋白尿增加，两者独立相关 与肾衰竭、慢性肾脏病并发症和心血管疾病的风险增加相结合 (CVD)。然而，总的来说，与年龄相关的肾功能改变的原因还不是很清楚。 部分，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 中心假说是老年人肾小球滤过率降低和蛋白尿增加反映了 终生暴露于心血管危险因素导致的肾脏微血管疾病， 部分是由于主动脉僵硬增加所致。 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)是一个 遗传流行病学研究嵌套在冰岛1967年开始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。这项研究包括一个全面的 中年心血管疾病危险因素的评估：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。我们建议进行一项辅助研究 本次访问。具体目标包括：1.根据年龄、性别和心血管疾病风险确定测量的GFR水平 各种因素。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在衰老中的负担。我们将测定所有受试者的肌酐、胱抑素C和蛋白尿(N=3484)。 将它们与CKD并发症、临床和亚临床CVD以及CVD危险因素联系起来，并比较结果 到可比的美国人口(NHANES 99-04)。3.将老年肾功能与中年和晚年联系起来 心血管疾病危险因素和老年主动脉僵硬。在940名受试者中，测量了主动脉僵硬 并将在本次访问中获得所有受试者的数据(N=3484)。 社区老年人代表性队列中GFR和主动脉僵硬的测量 个人将允许最准确地调查肾功能水平、慢性肾脏病负担、 以及肾功能随年龄增长而下降的潜在机制。这些信息对于 确定慢性肾脏病发展的可改变的风险因素，并制定有针对性的战略 用于预防和治疗老年人慢性肾脏病。首席调查员和研究团队是理想的 适合进行这项调查。他们的专业知识，加上独特的设计和全面的 在AGES-雷克雅未克研究中的评估，将允许对 肾功能、主动脉僵硬与年龄的关系。

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.