Investigations of the optimum serum bicarbonate level in renal disease

肾脏疾病最佳血清碳酸氢盐水平的研究

• 批准号: 8334733
• 负责人: Kalani Lukela Raphael
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334733
• 关键词: Acid-Base Equilibrium; Acids; Address; African American; Alkalies; Alternative Complement Pathway; Ammonia; Anatomy; Area; Attenuated; Basic Science; Bicarbonates; Biological; Blood; Blood Circulation; Bone Diseases; Catabolism; Cessation of life; Chronic; Chronic Kidney Failure; Cities; Clinical; Clinical Management; Clinical Research; Clinical Sciences; Complement; Complement Activation; Complex; Data; Dedications; Development; Development Plans; Diabetes Mellitus; Diabetic Nephropathy; Disease Progression; Elements; End stage renal failure; Excretory function; Faculty; Fibrosis; Gluconeogenesis; Glutamine; Goals; Human; Hypertension; Injury; Institution; Interdisciplinary Study; Intervention; Investigation; K-Series Research Career Programs; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Laboratories; Lead; Learning; Mediator of activation protein; Medicine; Mentors; Metabolism; Multicenter Trials; Nephrology; Nephrons; Normal Range; Observational Study; Oral; Outcome; Participant; Pathology; Pathway interactions; Patients; Physiological; Population; Process; Production; Prospective Studies; Proteins; Publications; Renin-Angiotensin-Aldosterone System; Research; Research Methodology; Research Personnel; Research Project Grants; Research Training; Residual state; Resources; Risk; Serum; Sodium Bicarbonate; Sodium Chloride; Suggestion; Supervision; Testing; Time; Training; Translational Research; Universities; Utah; Veterans; Writing; activation product; alpha ketoglutarate; base; blood pressure regulation; career development; comparative effectiveness; complement system; design; diabetic; effectiveness research; falls; group intervention; hazard; human TGFB1 protein; human disease; inhibitor/antagonist; innovation; member; novel strategies; novel therapeutics; premature; primary outcome; professor; prospective; randomized placebo controlled trial; research study; response; responsible research conduct; secondary outcome; skills; statistics; urinary

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. PUBLIC HEALTH RELEVANCE: Treatment with medicines that bring down high acid levels in the bloodstream of people with kidney disease might delay kidney failure. This research study will test to see if this treatment might be helpful in people with diabetes who have kidney disease and normal acid levels in the blood.

描述（由申请人提供）： 我是湖城和犹他州附属大学肾脏科的助理教授。2009年之前，我的研究背景是基础科学。在我的临床一年，我发现我想追求临床研究的额外培训。我的短期目标是通过在人类中进行回顾性、横断面和前瞻性研究来发展临床研究技能，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，我已确定Srinivasan Beddhu博士、Tom格林博士和Alfred Cheung博士作为我的指导团队。Beddhu博士一直担任主要导师，格林博士和张博士是共同导师。犹他州大学和弗吉尼亚州盐湖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），并致力于初级研究人员的发展。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的培训，负责任地进行研究的培训，参加研讨会，这将有助于我对统计学和替代临床研究方法有更深入的了解，参加一门课程，这将有助于我发展科学写作技能，进行前瞻性临床试验，进行观察性研究以扩大我的出版记录并获得该领域的曝光，最重要的是继续接受Beddhu，格林和Cheung博士的指导。 本提案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。它扩展了最近的研究，这些研究表明，低血清碳酸氢盐的碱性治疗可能会减缓慢性肾脏疾病的进展，以及我们的观察结果，即慢性肾脏疾病进展和死亡的风险与非裔美国人肾脏疾病和高血压研究（AASK）参与者的基线血清碳酸氢盐水平呈负相关。拟定的研究是一项在患有慢性肾脏疾病且血清碳酸氢盐在正常范围（22 - 28 mmol/L）的糖尿病受试者中进行的碳酸氢钠随机、安慰剂对照研究。将比较两组间尿转化生长因子-β 1和尿补体活化产物（Bb和MAC）的变化。我假设干预组的尿转化生长因子-β 1、Bb和MAC会降低。 总之，职业发展奖将使我能够将我之前在实验室的培训与目前在临床研究中的培训结合起来，以实现成为一名成功的翻译研究者的目标。我目前的重点领域是慢性肾脏病酸碱平衡的临床管理。随着我的导师和正在与资源和奉献精神，以促进年轻教师的发展机构的持续监督，我相信我会成功。 公共卫生关系： 用降低肾病患者血液中高酸水平的药物治疗可能会延缓肾衰竭。这项研究将测试这种治疗是否对患有肾脏疾病和血液中酸水平正常的糖尿病患者有帮助。