Modifiable and Biochemical Predictors and Consequences of Acute Kidney Injury

描述(由申请人提供)：在这份导师研究科学家发展奖(K01)的建议书中，Amanda Hyre Anderson博士，公共卫生硕士，概述了她的职业目标，职业发展计划，环境，指导框架，以及研究项目，以检验可改变的和生化的预测因素和慢性肾脏疾病(CKD)急性肾脏损伤(AKI)的后果。安德森博士在杜兰大学完成了流行病学的硕士和博士培训，获得了许多奖项和荣誉，并在宾夕法尼亚大学医学院完成了肾脏流行病学的NRSA博士后研究。她目前是宾夕法尼亚大学的研究助理和慢性肾功能不全队列(CRIC)研究的联合研究员。安德森博士计划从事独立研究人员的职业生涯，研究慢性肾脏病中AKI的流行病学，肾功能随时间的下降的特征和预测，以及未充分研究与慢性肾脏病相关的共病和结果(例如，非心血管并存)。她的长期目标是担任一个长期教职，成为一名积极的调查员。在获奖期间，为了使安德森博士能够从受指导的科学家转变为独立的研究人员，安德森博士将1)通过课程作业和肾脏病轮回寻求更多关于肾脏疾病的知识，2)通过课程作业和指导寻求更多复杂的统计方法，3)通过完成沃顿商学院的领导力发展项目并参与CRIC研究监督活动来增强她的领导能力，4)利用与导师和顾问的互动来完善她的研究计划并支持她的职业发展，以及5)提交R01申请以进一步发展她的独立研究项目。拟议的K01研究项目的总体目标是确定AKI的可修改和生化风险因素，并检查AKI对各种具有CKD特征的CRIC参与者的发病率和死亡率的影响。更具体地说，该项目的目标是：1)检查血糖控制不佳、血压控制不充分、体重指数升高，以及使用肾素血管紧张素系统阻滞剂、利尿剂和非类固醇抗炎药作为CKD中AKI的可改变的危险因素；2)调查炎症和肾脏损伤标志物以及CKD严重程度，作为CKD中AKI的危险因素；以及3)检查AKI对CKD继发死亡率和发病率的影响。所有拟议的调查都将在CRIC研究的队列框架内进行，使用的是Cox比例风险模型、混合影响增长曲线模型和具有时间更新风险的边际结构模型。在经历AKI的CRIC参与者中，将采用一种创新的混合效应方法来比较AKI发作前后肾功能下降的斜率。这项研究将使我们有可能确定AKI的潜在可改变的、从而临床可操作的危险因素，并提高我们对AKI在CKD病程中的影响的理解。

DESCRIPTION (provided by applicant): In this proposal for a Mentored Research Scientist Development Award (K01), Amanda Hyre Anderson, PhD, MPH, outlines her career goals, career development plan, environment, mentoring framework, and research project to examine modifiable and biochemical predictors and consequences of acute kidney injury (AKI) in chronic kidney disease (CKD). Dr. Anderson completed her master's and doctoral training in Epidemiology at Tulane University with numerous awards and honors, and finished a NRSA postdoctoral fellowship in Renal Epidemiology at the University of Pennsylvania School of Medicine. She is currently a Research Associate at Penn and a co-investigator on the Chronic Renal Insufficiency Cohort (CRIC) Study. Dr. Anderson plans to pursue a career as an independent investigator to study the epidemiology of AKI in CKD, characterization and prediction of kidney function decline over time, and insufficiently examined co-morbidities and outcomes (e.g., non-cardiovascular co-morbidities) associated with CKD. Her long-term goal is to hold a standing faculty position as an active investigator. To enable her transition from mentored scientist to independent investigator during the award period, Dr. Anderson will 1) seek an improved knowledge of renal disease through coursework and nephrology rounds, 2) pursue an expanded repertoire of sophisticated statistical methods through coursework and mentoring, 3) strengthen her leadership capabilities by completing a leadership development program through the Wharton School of Business and engaging in CRIC Study oversight activities, 4) leverage interactions with mentors and consultants to refine her research plan and support her career development, and 5) submit an R01 application to further her independent research program. The overall goal of the proposed K01 research project is to identify modifiable and biochemical risk factors for AKI, and to examine the impact of AKI on morbidity and mortality among a diverse group of extremely well- characterized CRIC participants with CKD. More specifically, the aims of the project are: 1) to examine poor glycemic control, inadequate control of blood pressure, elevated body mass index, and use of renin- angiotensin-system blockade, diuretics, and nonsteroidal anti-inflammatory drugs as modifiable risk factors for AKI in the setting of CKD, 2) to investigate inflammatory and kidney injury markers, as well as CKD severity, as risk factors for AKI in CKD, and 3) to examine the impact of AKI on subsequent mortality and morbidity in CKD. All proposed investigations will occur within the cohort framework of the CRIC Study utilizing Cox proportional hazards models, mixed effects growth curve models, and marginal structural models with time-updated exposures. An innovative mixed effects approach will be employed among CRIC participants who experience AKI during follow-up to compare the slope of kidney function decline before and after the AKI episode. This study will make possible the identification of potentially modifiable, and thus, clinically-actionable, risk factors for AKI, and improve our understanding of the impact of AKI on the course of CKD.