Investigations of the optimum serum bicarbonate level in renal disease

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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.