Novel Risk Factors for Kidney Stone Formation

描述(由申请人提供)： 埃里克·N·泰勒博士希望成为一名内科科学家，为肾脏疾病患者的护理做出实质性、持久的贡献。有指导的职业发展奖将使泰勒博士能够培养作为一名独立临床调查员的成功职业生涯的以下先决条件：1)生物统计学和流行病学方面的高级技能；2)有时间从事重点研究项目；3)由经验丰富、成功的临床研究人员进行密切的长期指导。 泰勒博士的研究兴趣是肾结石，这是一种常见的、昂贵的、痛苦的疾病。这项建议的目标是解决营养和肾结石领域的争议，并确定肾结石形成的新生活方式、激素和遗传危险因素。使用前瞻性研究设计，他将在三个大的队列中研究特定饮食和生活方式因素与症状性肾结石形成风险之间的关系：卫生专业人员跟踪研究(N=51,000名男性)、护士健康研究I(N=121,000名老年女性)和护士健康研究II(N=116,000名年轻女性)。这些因素包括草酸盐、非乳制品钙和植酸盐的饮食摄入量，以及非类固醇抗炎药(NSAIDs)的使用。此外，他还将使用嵌套式病例对照设计(N=1500)研究胰岛素抵抗(通过空腹血浆胰岛素水平来评估)与肾结石形成风险之间的关系。他还将研究维生素D受体和钙敏感受体基因的特定多态与肾结石发病风险之间的关系(N=3000)。最后，他将研究这些基因多态对24小时尿钙排泄的影响(N=1500)。 总体而言，泰勒博士预计，他的研究将带来预防结石疾病的更好策略。除了为泰勒博士提供在肾结石形成风险因素研究方面积累经验和专业知识的独特机会外，职业发展奖还将使他精通先进的流行病学和分析技术。在完成这一职业发展奖后，泰勒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调查员取得成功。

DESCRIPTION (provided by applicant): Dr. Eric N. Taylor hopes to become a physician-scientist who will make substantial, lasting contributions to the care of patients with renal disease. A mentored career development award will allow Dr. Taylor to develop the following prerequisites for a successful career as an independent clinical investigator: 1) advanced skills in biostatistics and epidemiology; 2) protected time to pursue a focused research program; and 3) close, long-term mentorship by experienced, successful clinical investigators. Dr. Taylor's research interest is nephrolithiasis, which is a common, costly, and painful disease. The goals of this proposal are to resolve controversies in the field of nutrition and nephrolithiasis and to identify novel lifestyle, hormonal, and genetic risk factors for kidney stone formation. Using a prospective study design, he will examine the association between specific dietary and lifestyle factors and the risk of symptomatic kidney stone formation in three large cohorts: the Health Professionals Follow-up Study (N=51,000 men), the Nurses' Health Study I (N= 121,000 older women), and the Nurses' Health Study II (N=116,000 younger women). These factors include the dietary intake of oxalate, non-dairy calcium, and phytate, and the use of non-steroidal anti-inflammatory drugs (NSAIDs). In addition, he will study the relation between insulin resistance, as assessed by fasting levels of plasma insulin, and the risk of kidney stone formation using a nested case-control design (N=1500). He also will examine the association between specific polymorphisms of the vitamin D receptor and the calcium-sensing receptor genes and the risk of incident nephrolithiasis (N=3000). Finally, he will examine the effect of these genetic polymorphisms on the 24-hour urinary excretion of calcium (N=1500). Overall, Dr. Taylor anticipates that his research will result in better strategies to prevent stone disease. In addition to providing Dr. Taylor a unique opportunity to develop experience and expertise in the study of risk factors for kidney stone formation, the career development award will allow him to become proficient with advanced epidemiologic and analytic techniques. At the completion of this career development award, Dr. Taylor will have a unique combination of skills and experience that will enable him to succeed as an independent clinical investigator.