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及其附属犹他大学肾病科的助理教授。 2009 年之前我的研究背景是基础科学。在我的临床年中，我发现我想接受临床研究方面的额外培训。我的短期目标是通过对人类进行回顾性、横断面和前瞻性研究来培养临床研究技能，并开始获得肾脏疾病酸碱管理领域的专业知识。 为了促进临床研究培训过程，我已经确定了博士。 Srinivasan Beddhu、Tom Greene 和 Alfred Cheung 是我的导师团队。 Beddhu 博士一直担任主要导师，Drs.格林和张是共同导师。犹他大学和弗吉尼亚州盐湖城拥有临床和转化科学中心等资源，专注于开发跨学科研究项目、国家临床和解剖病理学参考实验室（ARUP 实验室），并致力于培养初级研究人员。职业发展计划的关键要素包括完成 MSCI 学位和比较有效性研究培训、负责任的研究行为培训、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、参加有助于我培养科学写作技能的课程、进行前瞻性临床试验、进行观察性研究以扩大我的发表记录并获得该领域的曝光度，最重要的是继续接受 Dr. 的指导。 Beddhu、格林和张。 该提案中的研究项目开始解决我们在慢性肾脏病酸碱平衡最佳管理方面的知识空白。它扩展了最近的研究，这些研究表明，对低血清碳酸氢盐的人进行碱疗法可能会减缓慢性肾脏病的进展，并且我们观察到，在非裔美国人肾脏病和高血压研究 (AASK) 的参与者中，慢性肾脏病进展和死亡的风险与基线血清碳酸氢盐水平呈负相关。拟议的研究是一项针对患有慢性肾病且血清碳酸氢盐处于正常范围（22 - 28 mmol/L）的糖尿病参与者的碳酸氢钠的随机、安慰剂对照研究。将比较各组之间尿转化生长因子-β1 和尿补体激活产物（Bb 和 MAC）的变化。我假设干预组的尿转化生长因子-β1、Bb 和 MAC 会减少。 总之，职业发展奖将使我能够将之前在实验室的培训与当前的临床研究培训结合起来，以实现成为一名成功的转化研究者的目标。我目前的重点领域是慢性肾脏病酸碱平衡的临床管理。在我的导师的持续监督下，以及在一个拥有资源和奉献精神促进年轻教师发展的机构中，我相信我会取得成功。

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.