Longitudinal Study of Predictors and Consequences of Chronic Kidney Disease

慢性肾脏疾病(CKD)在美国估计有1900万成年人受到影响，并与 心血管疾病(CVD)和死亡率的风险增加。临床实践指南定义慢性肾脏病 蛋白尿和肾功能下降的基础，最常通过估计 肾小球滤过率(EGFR)采用血肌酐(Scr)。国家组织已经提议 将CKD纳入心血管疾病风险分层算法，但到目前为止还没有大型前瞻性研究结合 蛋白尿和估计肾小球滤过率的数据，以检查心血管疾病的发病率。最近对老年人的研究表明 半胱氨酸氨基转移酶C(CysC)可以提供对肾功能的评估，更能预测随后的GVD 事件比基于SCR的估计更高，这容易由于肌肉损失而产生偏差。CKD共享 CKD的几个危险因素和致病机制已被前瞻性研究 有限的。 社区动脉粥样硬化风险(ARIC)研究跟踪了15,792名非洲裔美国人和 并提供了关于慢性肾脏病风险因素和后果的重要数据。我们建议 收集新数据并进行系统分析，以实现以下目标： 1)调查流行的CKD作为以下疾病的独立危险因素的最新评估 1996-1998年检查了11,336名成年人的心血管疾病和死亡率。流行的CKD 是由肾功能下降(现有的Scr和拟议的CysC措施)的组合定义的 和肾脏损害(蛋白尿)。 2)在嵌套病例队列设计中测试6年内肾功能下降的新预测因素 包括-800例，根据CysC估算GFR和Lt；60ml/min/1.73m2。我们将把重点放在 炎症标志物和晚期糖基化终末产物(AGEs)，以及 3)确定预测CKD发病的染色体区域和遗传变异。通过扩展 我们将进行正在进行的基因分型：(A)通过混合连锁不平衡进行全基因组定位 非洲裔美国人(MALD)扫描和(B)-2000个基因的候选基因研究。积极的结果将 在其他已确定的队列中进行复制测试(杰克逊心脏研究、弗雷明翰心脏研究 和心血管心脏研究)。 该提案直接涉及与当前政策问题相关的几个问题，包括如何最好地 量化CKD并将其纳入CVD风险预测算法。此外，它还将提供急需的 将与更大的科学界共享关于CKD的血清学和遗传风险因素的数据，a 美国日益增长的公共卫生问题。

Chronic kidney disease (CKD) affects an estimated 19 million adults in the US, and is associated with an elevated risk of cardiovascular disease (CVD) and mortality. Clinical practice guidelines define CKD on the basis of both albuminuria and decreased kidney function, most frequently assessed by estimating the glomerular filtration rate (eGFR) using serum creatinine (SCr). National organizations have proposed including CKD in CVD risk stratification algorithms, but no large prospective studies to date have combined data on albuminuria and estimated GFR to examine CVD incidence. Recent studies in the elderly suggest Cystatin C (CysC) can provide estimates of kidney function that are more predictive of subsequent GVD events than estimates based on SCr, which are susceptible to biases due to muscle loss. CKD shares several risk factors and pathogenic mechanisms with CVD though the prospective studies of CKD have been limited. The Atherosclerosis Risk in Communities (ARIC) Study has followed 15,792 African Americansand Whites since 1987, and provided important data on CKD risk factors and consequences. We propose to collect new data and conduct systematic analyses to achieve the following aims: 1) Investigate a state of the art assessment of prevalent CKD as an independent risk factor for cardiovascular disease and mortality among 11,336 adults examined in 1996-1998. Prevalent CKD is defined by a combination of decreased kidney function (existing SCr and proposed CysC measures) and kidney damage (albuminuria). 2) Test novel predictors of declining kidney function over 6 years in a nested case-cohort design including -800 cases with estimated GFR<60 ml/min/1.73m2 based on CysC. We will focusing on markers of inflammation and advanced glycation end-products (AGEs), and 3) Identify chromosomal regions and genetic variants predictive of incident CKD. Byextending ongoing genotyping we will conduct: (A) genome wide Mapping by Admixture Linkage Disequilibrium (MALD) scan in African-Americansand (B) Candidate gene study of -2,000 genes. Positive results will be tested for replication in additional identified cohorts (Jackson Heart Study, Framingham Heart Study and the Cardiovascular Heart Study). This proposal directly addresses several questions relevant to current policy issues, including how best to quantify CKD and incorporate it into CVD risk prediction algorithms. In addition, it will provide much-needed data to be shared with the larger scientific community on serologic and genetic risk factors for CKD, a growing public health concern in the US.