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（由申请人提供）：慢性肾病 (CKD) 影响着美国约 1,900 万成年人，并且与心血管疾病 (CVD) 和死亡率的风险升高相关。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) 估算肾小球滤过率 (eGFR)。国家组织已提议将 CKD 纳入 CVD 风险分层算法，但迄今为止还没有大型前瞻性研究将蛋白尿数据和估计 GFR 数据结合起来检查 CVD 发病率。最近针对老年人的研究表明，胱抑素 C (CysC) 可以提供肾功能的估计，与基于 SCr 的估计相比，该估计更能预测随后的 GVD 事件，而 SCr 容易因肌肉损失而出现偏差。尽管 CKD 的前瞻性研究有限，但 CKD 与 CVD 有一些共同的危险因素和致病机制。自 1987 年以来，社区动脉粥样硬化风险 (ARIC) 研究对 15,792 名非裔美国人和白人进行了追踪，并提供了有关 CKD 风险因素和后果的重要数据。我们建议收集新数据并进行系统分析，以实现以下目标： 1) 对 1996-1998 年检查的 11,336 名成年人中流行的 CKD 作为心血管疾病和死亡的独立危险因素进行最先进的评估。流行性 CKD 的定义是肾功能下降（现有 SCr 和提议的 CysC 措施）和肾脏损伤（白蛋白尿）。 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子，其中包括 -800 例基于 CysC 估计 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 (AGE)，以及 3) 识别可预测 CKD 事件的染色体区域和遗传变异。通过扩展正在进行的基因分型，我们将进行：(A) 在非裔美国人中通过混合连锁不平衡 (MALD) 扫描进行全基因组作图，以及 (B) -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中进行复制测试（杰克逊心脏研究、弗雷明汉心脏研究和心血管心脏研究）。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，它将提供急需的数据，与更广泛的科学界共享有关 CKD 血清学和遗传风险因素的数据，CKD 是美国日益关注的公共卫生问题。