Acute Kidney Injury: A Novel Risk Factor for Cardiovascular Events

描述（由申请方提供）：急性肾损伤（阿基）是指肾功能突然下降。最近的人群流行病学研究表明，阿基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，阿基与住院期间的高死亡风险相关。最近的数据表明，阿基还与阿基发作后数月至数年的慢性肾脏疾病发展和/或加速的风险增加有关。然而，关于阿基的其他长期后果，包括其对心血管事件风险的影响，还有很多未知之处。我们的初步数据表明，需要透析的阿基与后续急性冠状动脉综合征的风险增加有关。在拟定的研究中，我们将使用两个互补的研究队列进一步检验阿基是心血管事件的新风险因素的假设。首先，在凯泽大学使用一个基于人口的大型队列， Permanente北方加州，我们将评估阿基发作的影响以及阿基的严重程度对后续心血管事件风险的影响。这项分析将通过检查阿基对不同动脉粥样硬化和非动脉粥样硬化心血管事件（包括急性冠状动脉综合征、卒中、外周动脉疾病和心力衰竭）的影响以及通过检查非透析需要的阿基作为风险因素的影响来扩展我们先前的工作 治疗心血管疾病其次，使用来自NIDDK资助的急性肾损伤评估、系列评价和后续后遗症联盟（ASSESS-AKI）的库存生物标本，这是一项多中心队列研究，重点关注出院后阿基的自然史，我们将测试可能将阿基发作与后续心血管事件相关的几种生化途径。这些途径涉及矿物质代谢失调（使用磷、全段甲状旁腺激素、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、白细胞介素-6和肿瘤坏死因子-？测量）。拟议的努力将建立阿基与心血管事件风险的关联，并阐明阿基可能影响心血管风险的潜在生物学途径。由于要研究的几种生物学途径可以使用现有的治疗方法进行修改，因此了解阿基与心血管疾病相关的途径有可能直接改善越来越多的阿基住院患者的护理。

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.