Mortality Effect of Renal Replacement Therapy for Acute Kidney Injury Initiated D

描述(由申请人提供)：急性肾损伤(AKI)是危重疾病的常见并发症，即使是轻微的AKI也会带来独立的死亡风险(1，2)。目前还没有明确证明可以改善AKI预后的治疗方法，尽管一旦出现少尿、严重氮质血症或严重的电解质异常，肾脏替代疗法(RRT)往往是必要的生命维持措施。急性肾损伤网络确定急性肾损伤的适应症和RRT的时机是一个优先研究课题。先前研究急性肾损伤的RRT时机的研究通常仅限于接受RRT的AKI患者，这使得他们无法评估这种治疗的适应症，以及治疗与不治疗的影响(3，4)。在AKI的背景下，重新设计了关于RRT的问题，我们设计了一项研究，以检查在中度代谢紊乱期间启动透析治疗对死亡率的影响，中度代谢紊乱的定义是急性肾损伤后、实验室异常可检测到但透析的绝对指征出现之前的一段时间。我们利用早期AKI期间临床实践中的变化，在需要RRT作为维持生命的措施之前，设计一项观察性研究，使我们能够实现以下特定目标：目标1：制定一个定义中度代谢紊乱的指标，并评估启动RRT之前中度代谢紊乱的持续时间和严重程度与死亡率的关系。我们将根据基于各种因素的接受透析的可能性的多元回归模型来创建评分，并使用该可能性来定义混乱程度。然后，我们将用这些方法评估中度紊乱的持续时间和严重紊乱的严重程度(在开始透析或出现严重紊乱时进行审查)对预测住院死亡率的影响。目的2：评估在中度代谢紊乱期间启动的肾脏替代疗法(RRT)对AKI危重患者住院死亡率的影响。拟议的研究项目将在申请人攻读临床流行病学理学硕士学位的背景下进行，在课堂上进行教学学习，重点是流行病学基础知识、研究设计以及研究的统计和分析方法，将加强和指导申请人的研究过程。申请者对这个项目的长期目标是收集和分析数据，准备出版手稿，并以数据为基础，作为未来申请K奖的一部分。 公共卫生相关性：本文建议的研究将对住院患者的急性肾损伤的治疗产生重大影响。目前，对于AKI后开始透析的适当时机的看法存在很大的分歧。这项研究将提供在中度代谢紊乱期间开始透析治疗的益处或危害的证据，促进我们对AKI综合征的理解，并帮助我们更始终如一地治疗患者。

DESCRIPTION (provided by applicant): Acute kidney injury (AKI) is a common complication of critical illness, with even minor degrees of AKI conferring an independent risk of death (1, 2). No therapy currently exists that has been definitively demonstrated to improve outcomes in AKI, although renal replacement therapy (RRT) is frequently necessary as a life-sustaining measure once oliguria, severe azotemia, or significant electrolyte abnormalities develop. Defining the indications for and timing of RRT in the setting of AKI is a priority research topic identified by the Acute Kidney Injury Network. Prior studies examining timing of RRT in acute kidney injury typically have been limited to patients with AKI who received RRT, rendering them unable to evaluate the indications for this therapy, and the impact of therapy versus no therapy (3, 4). Reframing the questions regarding RRT in the setting of AKI, we have designed a study to examine the impact on mortality of initiating dialysis therapy during a period of moderate metabolic disarray, defined as the period of time after acute kidney injury, when laboratory abnormalities are detectable, but before absolute indications for dialysis have arisen. We take advantage of the variations in clinical practice during early AKI prior to when RRT is required as a life-sustaining measure to design an observational study that will permit us to accomplish the following specific aims: Aim 1: Develop a metric defining moderate metabolic disarray and assess the association of duration and severity of moderate metabolic disarray prior to initiation of RRT with the rate of mortality. We will create a score based on a multiple regression model of likelihood to receive dialysis based on a variety of factors, and use that likelihood to define degree of disarray. We will then assess the impact of duration and severity of moderate disarray with these methods (censored at initiation of dialysis or development of severe disarray) on predicting in-hospital mortality. Aim 2: Assess the impact of renal replacement therapy (RRT) initiated during moderate metabolic disarray on in-hospital mortality in a cohort of critically ill patients with AKI The proposed research project will be in the context of the applicant working towards a Masters of Science in Clinical Epidemiology, whereby didactic learning in the classroom, focusing on fundamentals of epidemiology, study design, and statistical and analytic methods of research will enhance and guide the research process of the applicant. The long-term objectives of the applicant for this project are to collect and analyze the data, prepare manuscripts for publication, and build upon the data as part of a future application for a K award. PUBLIC HEALTH RELEVANCE: The proposed research herein will have a significant impact on the treatment of acute kidney injury in hospitalized patients. Currently, large variation exists in opinion on appropriate timing of initiation of dialysis after AKI. This study will provide evidence of benefit or harm from initiation of dialytic therapy during moderate metabolic disarray, advancing our understanding of the syndrome of AKI and helping us to more consistently treat patients.