Determinants of the Incidence and Outcome of Acute Renal Failure

描述(由申请人提供)： Sushrut Waikar博士在耶鲁大学医学院获得医学博士学位，在加州大学旧金山分校接受内科培训，并将于2006年7月1日加入比格姆妇女医院的肾病学系。他目前是哈佛大学公共卫生学院公共卫生硕士学位的候选人。导师：Gary Curhan博士是一位著名的肾脏流行病学家，有成功指导学员的长期记录。与为Waikar博士的咨询委员会挑选的一批领先的研究人员一起，Curhan博士将确保Waikar博士的研究培训、项目和整体职业发展的成功。研究：急性肾功能衰竭(ARF)是住院患者常见且往往具有破坏性的并发症。尽管在阐明ARF的流行病学和病理生理学方面做出了相当大的努力，但仍然存在重要的差距。这项建议旨在促进ARF研究的两个主要领域：1)解决有关种族/民族、性别和医院因素等尚未解决的流行病学问题，这些问题可能影响与ARF相关的发病率和死亡率；2)寻找新的尿液生物标志物，以便能够早期识别急性肾损伤(AKI)及其后果。出于具体目的1，我们将使用两个大型数据库来调查住院患者中ARF的流行病学：a)全国住院患者样本，这是美国最大的全付费住院管理数据库，每年有500万至800万入院数据；b)研究患者数据注册表，这是布里格姆妇女医院和马萨诸塞州综合医院开发的一个独特的数据库，其中包含超过300,000名患者的相关管理、用药和实验室数据。为了达到特定的目的2，我们将在一组有肾损伤风险的患者中检测四种肾小管损伤的标志物。我们将检测肾损伤分子1(Kim-1)、中性粒细胞明胶酶相关脂蛋白(NGAL)、基质金属蛋白酶-9(MMP-9)和N-乙酰-氨基葡萄糖苷酶(NAG)，以确定AKI在血肌酐(=0.5 mg/dL)升高前至少24小时的识别能力；我们还将测试尿生物标记物是否可以识别当前‘亚临床’肾损伤，以及尿生物标记物升高可能预示哪些关于临床结果的独立预后信息。在完成这一职业发展奖后，Waikar博士将拥有独特的技能和经验组合，这将使他能够作为一名独立的临床研究员取得成功。

DESCRIPTION (provided by applicant): Dr. Sushrut Waikar received his MD degree from Yale University School of Medicine, trained in internal medicine at the University of California, San Francisco, and will join the nephrology faculty at Bigham and Women's Hospital on July 1, 2006. He is currently a candidate for the MPH degree from the Harvard School of Public Health. Mentor: Dr. Gary Curhan is a renowned renal epidemiologist with a long track record of successfully mentoring trainees. Along with a team of leading researchers selected for Dr. Waikar's advisory committee, Dr. Curhan will ensure the success of Dr. Waikar's research training, project, and overall career development. Research: Acute renal failure (ARF) is a common and often devastating complication in hospitalized patients. Despite considerable research efforts to clarify the epidemiology and pathophysiology of ARF, important gaps remain. This proposal aims to contribute to two major areas in ARF research: 1) to address unresolved epidemiologic questions regarding race/ethnicity, sex, and hospital factors that may influence the incidence of and mortality associated with ARF; and 2) to identify novel urinary biomarkers to enable the early identification of acute kidney injury (AKI) and its consequences. For Specific Aim 1 we will use two large databases to investigate the epidemiology of ARF in hospitalized patients: a) the Nationwide Inpatient Sample, the largest all-payer administrative database of hospitalizations in the United States with data on 5 to 8 million admissions annually; and b) the Research Patient Data Registry, a unique database developed at Brigham and Women's Hospital and Massachusetts General Hospital which contains linked administrative, medication, and laboratory data on over 300,000 patients. For Specific Aim 2 we will test four markers of tubular injury in a spectrum of patients at risk of kidney injury. We will test kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and N-acetyl-glucosaminidase (NAG) for the ability to identify AKI at least 24 hours prior to a rise in serum creatinine of (= 0.5 mg/dL; we will also test whether urinary biomarkers can identify currently 'sub-clinical' kidney injury, and what independent prognostic information on clinical outcomes may be heralded by urinary biomarker elevations. At the completion of this career development award, Dr. Waikar will have a unique combination of skills and experience that will enable him to succeed as an independent clinical investigator.