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，即使轻微的AKI也会带来独立的死亡风险（1,2）。虽然肾脏替代疗法（RRT）在少尿、严重氮血症或显著电解质异常发生时经常作为维持生命的措施是必要的，但目前还没有确切的治疗方法可以改善AKI的预后。在AKI的情况下，确定RRT的适应症和时机是急性肾损伤网络确定的优先研究课题。先前关于急性肾损伤中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，我们重新定义了关于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开始透析治疗对死亡率的影响，定义为急性肾损伤后，当实验室异常可检测到，但在透析的绝对指证出现之前的一段时间。我们利用早期AKI期间临床实践的变化，在需要RRT作为维持生命的措施之前，设计了一项观察性研究，使我们能够实现以下具体目标：目标1：制定一个定义中度代谢紊乱的指标，并评估开始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。我们将基于基于多种因素的接受透析可能性的多元回归模型创建一个分数，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程度（在透析开始或严重紊乱发展时删除）对预测院内死亡率的影响。目标2:评估中度代谢紊乱期间开始的肾脏替代疗法（RRT）对急性肾损伤危重患者队列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，研究设计，研究的统计分析方法将加强和指导申请人的研究过程。本项目申请人的长期目标是收集和分析数据，准备出版稿件，并将这些数据作为未来申请K奖的一部分。

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.