Acute Kidney Injury: A Novel Risk Factor for Cardiovascular Events

描述(申请人提供)：急性肾损伤(AKI)是指肾功能突然下降。最近以人群为基础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与住院期间的高死亡风险有关。最近的数据表明，AKI还与AKI发病数月至数年后发展和/或加速发生慢性肾脏疾病的风险增加有关。然而，AKI的其他长期后果，包括其对心血管事件风险的影响，仍有许多未知之处。我们的初步数据表明，需要透析的AKI与随后的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，在Kaiser使用以人口为基础的大型队列 在加利福尼亚州北部，我们将评估AKI发作的影响以及AKI的严重性对后续心血管事件的风险。这项分析将通过检查AKI对不同的动脉粥样硬化性和非动脉粥样硬化性心血管事件的影响，包括急性冠脉综合征、中风、外周动脉疾病和心力衰竭，以及通过检查非需要透析的AKI作为危险因素的影响，来扩展我们先前的工作 用于心血管事件。其次，使用NIDDK资助的评估、系列评估和急性肾损伤联盟(EASSISH-AKI)的后续后遗症的生物标本，我们将测试几个可能与AKI发作和后续心血管事件相关的生化途径。这些途径包括矿物质代谢失调(使用磷、完整的甲状旁腺激素、25(OH)、1，25(OH)2和24，25(OH)2维生素D、成纤维细胞生长因子-23和胎球蛋白-A来测量)和炎症(通过高敏C-反应蛋白、白介素6和肿瘤坏死因子-？来测量)。拟议的努力将建立AKI与心血管事件风险之间的联系，并阐明AKI可能影响心血管风险的潜在生物学途径。由于要研究的几种生物途径可以使用现有的治疗方法进行修改，了解哪些途径将急性心肌梗死与心血管疾病联系起来，有可能直接改善越来越多的急性心肌梗死住院患者的护理。

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.