Kidney Tubule Cell Function and Future Risk of Acute Kidney Injury

这是亚历山大·布伦医学博士在德纳的指导下第二次提交CDA2申请 里夫金是圣地亚哥退伍军人医学中心的研究员。这项提案将使布伦博士成为 独立的临床调查员，并将严格评估肾小管功能障碍的标志物 与急性肾损伤的发展、进展和恢复有关。 候选人：布伦博士的职业目标是：1)提高对肾小管之间的联系的理解 功能障碍和AKI；2)熟练掌握新的生物标志物方法学并将其翻译给患者- 以研究为导向；3)获得生物标志物分析的先进统计方法方面的专业知识；4) 制定独立的研究计划。为了实现这些目标，他组建了一个多学科的 由主要导师Dena Rifkin组成的导师团队，Dena Rifkin是荣誉奖的领先退伍军人研究人员 在肾脏疾病的研究设计方面的资金和丰富的经验，以及以下其他共同导师 顾问：Joachim IX，肾脏疾病肾小管方面的成熟专家 临床试验的实施以及对收缩压干预试验(SPRINT)的认识 被用于目标1，并被用于目标2；Edward Siew，医学博士，临床研究和 AKI中的生物标记物在验证用于诊断的急性肺损伤生物标记物(有效)方面具有专业知识 AIM 3和罗尼特·卡茨博士，他是一位在肾脏研究、协作史方面拥有专业经验的统计学家 与Bullen博士、Rifkin博士和IX博士合作，以及使用SPRINT和有关数据的经验。 研究：Aki在CKD的非线性进展中起着重要作用。当时的因素，患者 对未来AKI风险的易感的健康的人不仅可能对AKI的风险有洞察力，而且对CKD也有帮助。 布伦博士的总体假设是，对肾小管细胞功能障碍的测量不仅可以为临床提供 对未来的AKI风险评估有用，但也可能为导致AKI的机制提供重要的见解 尖锐地，并促进了它的复苏。在目标1中，他将对飞行员评估的肾小管功能障碍的标记物进行扩展。 数据并检查标志物的纵向变化以确定肾小管功能恶化的轨迹 预测超过单一基准值的AKI。他之前在Sprint的工作评估了 稳定的门诊患者和继发AKI的风险，继发于脱水/低血压。在《目标2》中，他将扩大 他的研究旨在调查AKI的其他原因，评估肾小管细胞功能障碍与 健康时间和因感染而发生AKI的未来风险，这是退伍军人中AKI的常见原因。最后，在AIM中 3，他将在ICU入院时检查有效队列中的小管功能，并确定 功能标记物是否可预测急性肾损伤的短期风险，并决定肾小管功能障碍的标记物 在AKI发作期间的变化。

This is a second submission of a CDA2 application by Alexander Bullen MD, under the mentorship of Dena Rifkin, a researcher at VA Medical Center in San Diego. This proposal will establish Dr. Bullen as an independent clinical investigator and will rigorously evaluate how markers of tubular dysfunction are associated with development, progression, and recovery of acute kidney injury. Candidate: Dr. Bullen’s career goals are: 1) to improve understanding on associations between tubular dysfunction and AKI; 2) to become proficient at novel biomarkers methodology and translation to patient- oriented research; 3) to gain expertise in advanced statistical methods for biomarker analyses; and 4) to develop an independent research program. To accomplish these goals, he has assembled a multidisciplinary mentorship team comprised of a primary mentor, Dena Rifkin, a leading VA researcher with Merit Award funding and extensive experience in research design in kidney disease and the following additional co-mentors and advisors: Joachim Ix, an established expert on tubular aspect of kidney disease in design and implementation of clinical trials as well as insight to the Systolic Blood Pressure Intervention Trial (SPRINT) utilized for Aim 1 and REGARDS utilized for Aim 2; Edward Siew, MD, an expert in clinical research and biomarkers in AKI with expertise in the Validating Acute Lung Injury Biomarkers for Diagnosis (VALID) used for Aim 3, and Ronit Katz PhD, a statistician with expertise experience in kidney research, collaborative history with Drs. Bullen, Rifkin, and Ix, and experience in utilizing the SPRINT and REGARDS data. Research: AKI plays an important role in the non-linear progression of CKD. Factors at the time when patients are healthy that predispose to future AKI risk are likely to give insights not only to risk of AKI but also to CKD. Dr. Bullen’s overall hypothesis is that measurement of tubular cell dysfunction may not only provide clinical utility for future AKI risk assessment but may also provide important insights to mechanisms leading to AKI acutely, and to its recovery. In Aim 1, he will expand upon the markers of tubule dysfunction evaluated in pilot data and examine longitudinal changes in markers to determine if trajectories of worsening tubule function predict AKI above and beyond a single baseline value. His prior work in SPRINT evaluates tubule function in stable outpatients and risk for subsequent AKI secondary to dehydration/hypotension. In Aim 2, he will expand his research to investigate other causes of AKI, evaluating the association between tubule cell dysfunction at times of health and future risk of AKI due to infection, a common cause of AKI among Veterans. Finally, in Aim 3, he will examine tubule function at the time of ICU admission among the VALID cohort and determine whether the function markers predict short-term risk of AKI and determine how tubule dysfunction markers change during episodes of AKI.