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: 7470898
• 负责人: Brad C Astor
• 金额: $ 3.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470898
• 关键词: Address; Admixture; Adult; Advanced Glycosylation End Products; Affect; African; African American; Age; Albuminuria; Algorithms; Arts; Atherosclerosis; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Chronic Kidney Failure; Classification; Clinical Practice Guideline; Communities; Condition; 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; Genome; 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; Participant; Pathway interactions; Play; Policies; Population; Procedures; Prospective Studies; Public Health; Race; Range; 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; glomerulosclerosis; glycation; mortality; novel; post gamma-globulins; programs; sex; vascular inflammation

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.

慢性肾脏疾病（CKD）影响着美国约1900万成年人，并与以下疾病相关： 心血管疾病（CVD）和死亡率的风险升高。临床实践指南将CKD定义为 蛋白尿和肾功能下降的基础，最常通过估计 使用血清肌酐（SCr）测定肾小球滤过率（eGFR）。国家组织建议 在CVD风险分层算法中包括CKD，但迄今为止还没有大型前瞻性研究结合 白蛋白尿和估计GFR的数据，以检查CVD发病率。最近对老年人的研究表明， 半胱氨酸蛋白酶抑制剂C（CysC）可以提供肾功能的估计，更能预测随后的GVD 事件比基于SCr的估计更容易受到肌肉损失引起的偏差的影响。CKD股份 尽管CKD的前瞻性研究已经发现了CVD的几个危险因素和致病机制， 有限公司 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， 自1987年以来，白人，并提供了重要的数据，CKD的风险因素和后果。我们建议 收集新数据并进行系统分析，以实现以下目标： 1)调查流行性CKD作为独立风险因素的最新评估， 1996-1998年对11，336名成年人进行的心血管疾病和死亡率调查。现患CKD 定义为肾功能下降（现有SCr和拟定CysC指标） 和肾损伤（蛋白尿）。 2)在巢式病例队列设计中检验6年以上肾功能下降的新预测因子 包括-800例基于CysC估计的GFR<60 ml/min/1.73m2的病例。我们将重点关注 炎症标志物和晚期糖基化终产物（AGEs），以及 3)确定预测CKD事件的染色体区域和遗传变异。通过扩展 我们将继续进行基因分型：（A）混合连锁不平衡全基因组定位 （B）对约2，000个基因的候选基因研究。积极的结果将 在其他确定的队列中进行复制试验（杰克逊心脏研究，心脏研究 心血管心脏研究）。 这项建议直接涉及与当前政策问题有关的几个问题，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 与更大的科学界分享关于CKD血清学和遗传风险因素的数据， 美国公众健康问题日益严重。