Acute Kidney Injury: A Novel Risk Factor for Cardiovascular Events

急性肾损伤：心血管事件的新危险因素

• 批准号: 8759177
• 负责人: Kathleen D Liu
• 金额: $ 59.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8759177
• 关键词: Acceleration; Accounting; Acute Renal Failure with Renal Papillary Necrosis; Biochemical Pathway; Biological; Biological Markers; C-reactive protein; California; Cardiovascular Diseases; Cardiovascular system; Caring; Cessation of life; Characteristics; Chronic Kidney Failure; Clinical; Cohort Studies; Complement; Data; Development; Dialysis procedure; Dimensions; Disease Progression; Evaluation; Event; Funding; Future; Heart failure; Hormones; Hospitalization; Hospitals; Incidence; Inflammation; Inflammatory; Integrated Delivery of Health Care; Integrated Health Care Systems; Interleukin-6; Investigation; Light; Link; Measures; Metabolism; Minerals; Modification; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Outcome; Parathyroid gland; Participant; Pathway Analysis; Pathway interactions; Patients; Peripheral arterial disease; Persons; Phosphorus; Plasma; Population; Public Health; Renal function; Research; Risk; Risk Factors; Sampling; Series; Severities; Staging; Stroke; System; Testing; Therapeutic; Tumor Necrosis Factor-alpha; Vitamin D2; Work; acute coronary syndrome; alpha-Fetoproteins; base; cardiovascular disorder risk; cardiovascular risk factor; cohort; epidemiology study; experience; fibroblast growth factor 23; follow-up; high risk; human subject; improved; indexing; novel; novel therapeutic intervention; patient population; population based; prospective; public health relevance

DESCRIPTION (provided by applicant): Acute kidney injury (AKI) refers to a sudden decrease in kidney function. Recent population-based epidemiology studies show that the incidence of AKI is rising rapidly, thus emphasizing its clinical and public health importance. AKI is well known to be associated with a high risk of death during hospitalization. More recent data indicate that AKI is also associated with an increased risk of development of and/or acceleration of chronic kidney disease months to years after the AKI episode. However, much remains unknown about other long-term consequences of AKI, including its impact on the risk of cardiovascular events. Our preliminary data demonstrate that dialysis-requiring AKI is associated with an increased risk of subsequent acute coronary syndromes. In the proposed studies, we will use two complementary study cohorts to further test the hypothesis that AKI is a novel risk factor for cardiovascular events. First, using a large population-based cohort at Kaiser Permanente Northern California, we will evaluate the impact of an episode of AKI as well as the severity of AKI on the risk of subsequent cardiovascular events. This analysis will extend our prior work by examining the impact of AKI on different atherosclerotic and non-atherosclerotic cardiovascular events, including acute coronary syndromes, stroke, peripheral arterial disease, and heart failure as well as by examining the impact of non-dialysis-requiring AKI as a risk factor for cardiovascular events. Second, using banked biospecimens from the NIDDK-funded Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Consortium (ASSESS-AKI), a multicenter cohort study focused on the natural history of AKI after hospital discharge, we will test several biochemical pathways that may associate an episode of AKI with subsequent cardiovascular events. These pathways involve dysregulated mineral metabolism (measured using phosphorus, intact parathyroid hormone, 25(OH), 1,25(OH)2 and 24,25(OH)2 vitamin D, FGF-23 and fetuin-A) and inflammation (measured through high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-?). The proposed efforts will establish the association of AKI with the risk for cardiovascular events as well as shed light on the potential biological pathways through which AKI may impact cardiovascular risk. Since several of the biological pathways to be studied are modifiable using currently available therapies, understanding which pathways associate AKI with cardiovascular disease has the potential to directly improve the care of the growing number of hospitalized patients who suffer an episode of AKI.

描述（申请人提供）： 急性肾损伤（AKI）是指肾功能突然下降。最近基于人群的流行病学研究表明，AKI 的发病率正在迅速上升，从而强调了其临床和公共卫生的重要性。众所周知，AKI 与住院期间死亡的高风险有关。最近的数据表明，AKI 还与 AKI 发作后数月至数年慢性肾病发展和/或加速的风险增加有关。然而，对于 AKI 的其他长期后果，包括其对心血管事件风险的影响，仍知之甚少。我们的初步数据表明，需要透析的 AKI 与随后发生急性冠状动脉综合征的风险增加有关。在拟议的研究中，我们将使用两个互补的研究队列来进一步检验 AKI 是心血管事件的新危险因素的假设。首先，使用 Kaiser 的大量基于人群的队列 在北加州永久医院，我们将评估 AKI 发作的影响以及 AKI 的严重程度对后续心血管事件风险的影响。该分析将通过检查 AKI 对不同动脉粥样硬化和非动脉粥样硬化心血管事件（包括急性冠脉综合征、中风、外周动脉疾病和心力衰竭）的影响以及检查非透析 AKI 作为危险因素的影响来扩展我们之前的工作 对于心血管事件。其次，使用来自 NIDDK 资助的急性肾损伤评估、系列评估和后续后遗症联盟 (ASSESS-AKI) 的生物样本，这是一项多中心队列研究，重点关注出院后 AKI 的自然史，我们将测试可能将 AKI 发作与随后的心血管事件相关的几种生化途径。这些途径涉及失调的矿物质代谢（使用磷、完整甲状旁腺激素、25(OH)、1,25(OH)2 和 24,25(OH)2 维生素 D、FGF-23 和胎球蛋白-A 测量）和炎症（通过高敏 C 反应蛋白、白介素-6 和肿瘤坏死因子-? 测量）。拟议的工作将建立 AKI 与心血管事件风险的关联，并阐明 AKI 可能影响心血管风险的潜在生物学途径。由于要研究的一些生物学途径可以使用现有的疗法进行修改，因此了解哪些途径将 AKI 与心血管疾病相关联，有可能直接改善越来越多患有 AKI 发作的住院患者的护理。