Longitudinal Study of Predictors and Consequences of Chronic Kidney Disease

慢性肾脏病的预测因素和后果的纵向研究

• 批准号: 8145010
• 负责人: Brad C Astor
• 金额: $ 22.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145010
• 关键词: Address; Admixture; Adult; Advanced Glycosylation End Products; Affect; African American; Age; Albuminuria; Algorithms; Arts; Atherosclerosis; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Chronic Kidney Failure; Clinical Practice Guideline; Communities; Coronary heart disease; Creatinine; Data; Databases; Diabetes Mellitus; Discipline; Disease Marker; Disease Outcome; Elderly; Epidemiology; Event; Framingham Heart Study; Functional disorder; General Population; Genes; Genetic Markers; Genotype; Glomerular Filtration Rate; Heart; Hyperglycemia; Hypertension; Incidence; Individual Differences; Inflammation; Institution; Interleukin-6; Interstitial Collagenase; Kidney; Kidney Diseases; Lead; Linkage Disequilibrium; Longitudinal Studies; Maps; Measurement; Measures; Muscle; N(6)-carboxymethyllysine; National Heart, Lung, and Blood Institute; Participant; Pathway interactions; Play; Policies; Population; Procedures; Prospective Studies; Public Health; Race; Renal function; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Scanning; Serological; Serum; Stratification; Testing; base; cardiovascular disorder risk; cohort; design; disorder risk; follow-up; genetic risk factor; genetic variant; genome wide association study; genome-wide; glomerulosclerosis; glycation; inflammatory marker; mortality; muscle form; novel; novel marker; population based; post gamma-globulins; programs; serological marker; sex; vascular inflammation

DESCRIPTION (provided by applicant): 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 Americans and 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. By extending ongoing genotyping we will conduct: (A) genome wide Mapping by Admixture Linkage Disequilibrium (MALD) scan in African-Americans and (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.

描述(申请人提供)：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有关。临床实践指南根据蛋白尿和肾功能下降来定义CKD，最常见的评估方法是使用血清肌酐(Scr)估计肾小球滤过率(EGFR)。国家组织已经提议将CKD纳入CVD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数据和估计的GFR来检查CVD发病率。最近在老年人中的研究表明，Cystatin C(CysC)可以提供比基于Scr的估计更能预测后续GVD事件的肾功能估计，SCR容易因肌肉丧失而产生偏差。CKD与CVD有许多共同的危险因素和发病机制，但对CKD的前瞻性研究一直很有限。自1987年以来，社区动脉粥样硬化风险(ARIC)研究跟踪了15,792名非裔美国人和白人，并提供了有关CKD风险因素和后果的重要数据。我们建议收集新的数据并进行系统分析，以实现以下目标：1)调查1996-1998年间接受检查的11,336名成年人中普遍存在的慢性肾脏病作为心血管疾病和死亡率的独立危险因素的最新评估。流行的CKD是由肾功能降低(现有的Scr和建议的CysC措施)和肾脏损害(蛋白尿)的组合定义的。2)采用嵌套式病例队列设计，对6年内肾功能下降的新预测因素进行测试，包括800例患者，以CysC为基础估计GFR和Lt；60ml/min/1.73m2。我们将专注于炎症和晚期糖基化终末产物(AGEs)的标记物，以及3)识别预测CKD发生的染色体区域和遗传变异。通过扩大正在进行的基因分型，我们将进行：(A)通过混合连锁不平衡(MALD)扫描在非裔美国人中进行全基因组定位和(B)对-2,000个基因的候选基因研究。阳性结果将在其他已确定的队列(杰克逊心脏研究、弗雷明翰心脏研究和心血管心脏研究)中进行复制测试。该提案直接解决了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，它还将提供急需的数据，以便与更大的科学界共享CKD的血清学和遗传风险因素，CKD在美国是一个日益严重的公共卫生问题。