Determinants of the Incidence and Outcome of Acute Renal Failure

描述（由申请人提供）： 博士Sushrut Waikar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弗朗西斯科接受内科培训，并将于2006年7月1日加入Bigham妇女医院的肾脏病学系。他目前是哈佛公共卫生学院公共卫生硕士学位的候选人。导师：加里柯汉博士是一位著名的肾脏流行病学家，长期以来一直成功地指导学员。沿着入选Waikar博士顾问委员会的主要研究人员团队，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）是住院患者常见的，往往是毁灭性的并发症。尽管进行了大量研究来阐明ARF的流行病学和病理生理学，但仍然存在重要差距。该提案旨在为ARF研究的两个主要领域做出贡献：1）解决可能影响ARF相关发病率和死亡率的种族/民族、性别和医院因素等尚未解决的流行病学问题; 2）确定新的尿液生物标志物，以早期识别急性肾损伤（阿基）及其后果。对于具体目标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，这是美国最大的住院全付费管理数据库，每年有500万至800万住院患者的数据;和B）研究患者数据登记处，布里格姆妇女医院和马萨诸塞州总医院开发的一个独特的数据库，其中包含超过30万名患者的相关管理、药物和实验室数据。对于特定目标2，我们将在一系列有肾损伤风险的患者中检测四种肾小管损伤标志物。我们将检测肾损伤分子1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、基质金属蛋白酶-9（MMP-9）和N-乙酰氨基葡萄糖苷酶（NAG）在血清肌酐升高（≥ 0.5 mg/dL;我们还将测试尿生物标志物是否可以识别目前的“亚临床”肾损伤，以及尿生物标志物升高可能预示临床结果的独立预后信息。在这个职业发展奖完成后，Waikar博士将拥有独特的技能和经验，使他能够成功地成为一名独立的临床研究者。

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.