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（K 01）的提案中，阿曼达Hyre安德森博士，公共卫生硕士，概述了她的职业目标，职业发展计划，环境，指导框架和研究项目，以检查慢性肾脏病（CKD）中急性肾损伤（阿基）的可修改和生化预测因子和后果。安德森博士在杜兰大学完成了流行病学硕士和博士培训，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，也是慢性肾功能不全队列（CRIC）研究的共同研究者。安德森博士计划从事独立研究者的职业生涯，研究CKD中阿基的流行病学，肾功能随时间下降的表征和预测，以及未充分检查的合并症和结局（例如，非心血管合并症）。她的长期目标是作为一名积极的调查员担任常设教师职位。为了使她能够在获奖期间从指导科学家过渡到独立研究者，安德森博士将1）通过课程和肾脏病学查房寻求改善肾脏疾病的知识，2）通过课程和指导追求复杂统计方法的扩展曲目，第三章通过沃顿商学院完成领导力发展计划并参与CRIC研究，加强她的领导能力监督活动，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R 01申请以进一步推进她的独立研究计划。拟议的K 01研究项目的总体目标是确定阿基的可改变和生化风险因素，并检查阿基对不同人群中发病率和死亡率的影响，这些人群均具有非常好的特征，患有CKD的CRIC参与者。更具体地说，该项目的目标是：1）检查血糖控制不良、血压控制不充分、体重指数升高以及使用肾素-血管紧张素系统阻断剂、利尿剂和非甾体抗炎药作为CKD背景下阿基的可改变风险因素，2）研究炎症和肾损伤标志物以及CKD严重程度作为CKD中阿基的风险因素，以及3）检查阿基对CKD患者随后的死亡率和发病率的影响。所有拟定的研究将在CRIC研究的队列框架内进行，使用考克斯比例风险模型、混合效应增长曲线模型和具有时间更新暴露的边际结构模型。将在随访期间发生阿基的CRIC参与者中采用创新的混合效应方法，以比较阿基发作前后肾功能下降的斜率。这项研究将有可能确定潜在的可改变的，因此，临床上可操作的阿基风险因素，并提高我们对阿基对CKD病程影响的理解。

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.