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）： 我是弗吉尼亚州盐湖城肾脏科学系和犹他大学肾脏科学系的助理教授。我的研究背景直到2009年是基础科学。在临床年份，我发现我想在临床研究中进行其他培训。我的短Tem目标是通过对人类进行回顾性，横断面和前瞻性研究来发展临床研究的技能，并开始在肾脏疾病中酸碱管理领域获得专业知识。 为了促进临床研究培训过程，我已经确定了Drs。 Srinivasan Beddhu，Tom Greene和Alfred Cheung是我的指导团队。 Beddhu博士一直担任主要导师和博士。 Greene和Cheung是联合官员。犹他大学和盐湖城弗吉尼亚大学拥有临床和转化科学中心等资源，重点是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），并致力于开发初级研究者。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中的培训，负责任的研究培训，参加研讨会，将有助于我对我对统计和替代性临床研究方法的更复杂的理解，从而有助于我采用一门课程，从而帮助我通过探索和扩展型号，以扩大前瞻性临床研究，从而扩大了探索，以扩大探索，以扩大探索，以扩大观察性，以扩大良好的态度，以实现观察性的研究，以实现观察的范围，以实现观察的范围，以实现观察的范围。博士。 Beddhu，Greene和Cheung。 该提案中的研究项目开始解决我们有关慢性肾脏疾病酸碱平衡的最佳管理的知识差距。它扩展了最近的研究，该研究表明，血清碳酸氢盐低的碱性疗法可能会减缓慢性肾脏疾病的进展，我们的观察结果是，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成反比，这与非裔美国肾脏疾病和高血压研究的参与者（AASK）。该研究提出的是一项在正常范围内患有慢性肾脏疾病和血清碳酸氢盐的糖尿病参与者中碳酸氢钠的随机，安慰剂对照研究（22-28 mmol/L）。两组之间将比较尿转化生长因子-BETA1和尿补体激活产物（BB和MAC）的变化。我假设干预组将减少尿转化生长因子-BETA1，BB和MAC。 总而言之，职业发展奖将使我能够与目前在临床研究中的培训中嫁给我在实验室的先前培训，以实现成为成功的转化调查员的目标。我目前的重点是慢性肾脏疾病中酸碱平衡的临床管理。在我的导师的持续监督下，并在一个拥有资源和奉献精神的机构中，我相信自己会成功。 公共卫生相关性： 用肾脏疾病患者血液中高酸水平的药物治疗可能会延迟肾衰竭。这项研究将测试，以查看这种治疗方法是否对血液中患有肾脏疾病和正常酸水平的糖尿病患者有帮助。