Investigations of the optimum serum bicarbonate level in renal disease

描述(由申请人提供)： 我是弗吉尼亚州盐湖城大学和犹他州附属大学肾脏科的助理教授。在2009年之前，我的研究背景是基础科学。在我的临床年里，我发现我想要在临床研究方面进行更多的培训。我的短期目标是通过在人类身上进行回顾、横断面和前瞻性研究来发展临床研究的技能，并开始在肾脏疾病的酸碱管理领域获得专业知识。为了促进临床研究培训过程，我已经指定斯里尼瓦桑·贝德胡博士、汤姆·格林博士和阿尔弗雷德·张博士作为我的指导团队。贝德胡博士一直担任主要导师，格林博士和张博士是联合导师。犹他大学和弗吉尼亚州盐湖城拥有的资源包括临床和翻译科学中心，专注于发展跨学科研究项目，国家临床和解剖病理学参考实验室(ARUP实验室)，以及致力于发展初级研究人员。职业发展计划的关键要素包括完成MSCI学位和接受比较有效性研究的培训，接受负责任的研究工作培训，参加有助于我对统计学和替代临床研究方法有更深入了解的研讨会，参加有助于我发展科学写作技能的课程，进行前瞻性临床试验，开展观察性研究以扩大我的出版记录并获得在该领域的曝光率，以及最重要的是继续接受Beddhu、Greene和Cheung博士的指导。这项建议中的研究项目开始解决我们在慢性肾脏疾病酸碱平衡最佳管理方面的知识空白。它对最近的研究进行了扩展，这些研究表明，对血清碳酸氢盐水平较低的人进行碱性治疗可能会减缓慢性肾脏疾病的进展，我们观察到，在非裔美国人肾脏疾病和高血压研究(AASK)的参与者中，慢性肾脏疾病进展和死亡的风险与基线血清碳酸氢盐水平呈负相关。这项研究是一项随机、安慰剂对照研究，适用于患有慢性肾脏疾病且血清碳酸氢盐在正常范围(22-28 mmoL/L)的糖尿病患者。比较两组间尿转化生长因子-β1和尿补体激活产物(BB和MAC)的变化。我假设干预组的尿中转化生长因子-β1、BB和MAC会减少。总而言之，职业发展奖将使我能够将我以前在实验室接受的培训与目前的临床研究培训结合起来，实现成为一名成功的翻译研究员的目标。我目前关注的领域是慢性肾脏疾病的酸碱平衡的临床管理。在导师的持续监督下，通过在一所拥有资源和奉献精神的机构促进年轻教职员工的发展，我有信心我会成功。

DESCRIPTION (provided by applicant): I am an Assistant Professor in the Division of Nephrology at the Salt Lake City VA and affiliated University of Utah. My research background until 2009 was in the basic sciences. During my clinical year I found that I wanted to pursue additional training in clinical research. My short-tem goals are to develop skills in clinical research by conducting retrospective, cross-sectional, and prospective studies in humans and to begin to achieve expertise in the area of acid-base management in renal disease. To facilitate the clinical research training process, I have identified Drs. Srinivasan Beddhu, Tom Greene, and Alfred Cheung as my mentoring team. Dr. Beddhu has been serving as the primary mentor and Drs. Greene and Cheung are co-mentors. The University of Utah and Salt Lake City VA have resources such as the Center for Clinical and Translational Sciences, a focus on developing interdisciplinary research projects, a national clinical and anatomic pathology reference laboratory (ARUP Laboratories), and a commitment to the development of junior investigators. Key elements of the career development plan include completion of the MSCI degree and training in comparative effectiveness research, training in the responsible conduct of research, attending seminars that will help me develop a more sophisticated understanding of statistics and alternative clinical research methodologies, taking a course that will help me develop skills in scientific writing, performing prospective clinical trals, conducting observational studies to expand my publication record and gain exposure in the field, and most importantly continuing to be mentored by Drs. Beddhu, Greene, and Cheung. The research project in this proposal begins to address gaps in our knowledge regarding the optimum management of acid-base balance in chronic kidney disease. It expands on recent studies that suggest that alkaline therapy in those with low serum bicarbonate might slow chronic kidney disease progression, and our observation that the risk of chronic kidney disease progression and death was inversely related to baseline serum bicarbonate level among participants in the African American Study of Kidney Disease and Hypertension (AASK). The study proposed is a randomized, placebo-controlled study of sodium bicarbonate in diabetic participants with chronic kidney disease and serum bicarbonate in the normal range (22 - 28 mmol/L). Changes in urinary transforming growth factor-beta1 and urinary complement activation products (Bb and MAC) will be compared between the groups. I hypothesize that the intervention group will have reductions in urinary transforming growth factor-beta1, Bb, and MAC. In summary, the career development award will allow me to marry my prior training in the laboratory with current training in clinical research to achieve the goal of becoming a successful translational investigator. My current area of focus is in the clinical management of acid-base balance in chronic kidney disease. With continued supervision by my mentors and by being at an institution with the resources and dedication to facilitate the development of young faculty members, I am confident that I will be successful.