Sodium Nitrite Supplementation for Improving Physiological Function in Patients with Chronic Kidney Disease

补充亚硝酸钠改善慢性肾病患者的生理功能

• 批准号: 10669389
• 负责人: Matthew J Rossman
• 金额: $ 16.22万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10669389
• 关键词: Acute; Age; Aging; Anions; Antioxidants; Arteries; Ascorbic Acid; Biological; Biological Availability; Biology; Biomedical Research; Biometry; Blood Circulation; Blood Vessels; Cardiovascular Diseases; Carotid Arteries; Cause of Death; Center for Translational Science Activities; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Cognitive; Colorado; Conduct Clinical Trials; Consult; Data; Development; Development Plans; Disease; Doctor of Philosophy; Double-Blind Method; Elderly; Endothelium; Environment; Episodic memory; Equilibrium; Extramural Activities; Faculty; Functional disorder; Funding; Glomerular Filtration Rate; Goals; Human; Impaired cognition; Impairment; Infusion procedures; International; Intervention; Journals; Kidney; Kidney Diseases; Laboratories; Life Style; Mediating; Mentors; Mentorship; Modeling; Morbidity - disease rate; Motor; Movement; Mus; Nephrectomy; Nitrates; Nitric Oxide; Nitrites; Operative Surgical Procedures; Oral; Oxidative Stress; Patients; Performance; Pharmacology; Physiologic pulse; Physiological; Physiology; Placebo Control; Placebos; Postdoctoral Fellow; Property; Publishing; Randomized; Randomized Clinical Trials; Records; Renal Hypertension; Renal function; Research; Research Personnel; Research Project Grants; Research Training; Safety; Scientist; Short-Term Memory; Signaling Molecule; Sodium Nitrite; Supplementation; Testing; Therapeutic; Tissues; Training; United States National Institutes of Health; Universities; Vascular Diseases; Vascular Endothelial Cell; Vascular Endothelium; arterial stiffness; base; brachial artery; cardiovascular disorder risk; career development; circulating biomarkers; clinical risk; clinically relevant; cognitive function; comorbidity; design; disability; disability risk; efficacy evaluation; efficacy testing; evidence base; executive function; experience; improved; indexing; innovation; insight; meetings; mid-career faculty; middle age; mortality; motor disorder; novel; novel strategies; oral supplementation; oxidation; patient population; physically handicapped; preservation; prevent; processing speed; programs; seal; skill acquisition; skills; therapy development; vascular endothelial dysfunction

CANDIDATE: Matthew J. Rossman, Ph.D., is a postdoctoral fellow training in the integrative physiology of aging at the University of Colorado (CU) Boulder. In this K01 application, Dr. Rossman aims to determine the efficacy of a novel nitric oxide (NO) boosting compound, sodium nitrite, for improving vascular, motor (physical) and cognitive function in patients with chronic kidney disease (CKD). His immediate goal is to acquire the research training and professional skills necessary to transition to an independent, extramurally funded investigator. His long-­term goal is to establish his own research program with a focus on identifying novel, evidence-­based lifestyle and pharmacological interventions that prevent or delay the development of vascular, motor and cognitive dysfunction to reduce the risk of CVD and other comorbidities in CKD. CAREER DEVELOPMENT PLAN: Dr. Rossman’s career development plan consists of: 1) acquiring new research skills associated with the proposed research plan;; 2) training in renal physiology, CKD, motor and cognitive function, clinical trials and biostatistics through coursework and meetings with his mentorship team;; and 3) professional skill development through coursework;; attendance/presentations at weekly journal clubs, CU seminars and national scientific meetings;; and regular interactions with his mentor team. ENVIRONMENT: The environment for Dr. Rossman’s training plan will be outstanding. Dr. Rossman’s primary mentor Dr. Douglas Seals and his co-­mentor Dr. Michel Chonchol are internationally recognized, NIH funded scientists with strong records of successful mentoring in translational biomedical research pertaining to age-­ and disease-­related physiological dysfunction and CKD. Dr. Chonchol is also a board-­certified nephrologist and Director of Clinical Research in the Division of Renal Diseases and Hypertension at CU Denver. Consulting mentor Dr. McQueen is director of biostatistics at the CU Boulder Clinical & Translational Research Center and regularly provides mentoring/consulting to trainees and faculty conducting clinical trials. Consulting mentor Dr. Tamura is an associate professor at Stanford University with extensive experience assessing motor and cognitive function in patients with CKD. Consulting mentor Dr. Bryan is an expert in nitrite/NO biology and improving physiological function via nitrite supplementation. RESEARCH: CKD is a highly prevalent condition and CVD is the leading cause of death in patients with CKD. Increased CVD risk in CKD is largely attributable to the development of vascular dysfunction, primarily vascular endothelial dysfunction and large elastic artery stiffening. Reduced motor and cognitive function are also common in CKD and increase the risk of disability and mortality in these patients. Vascular, motor and cognitive dysfunction all are related to reduced NO bioavailability. Nitrite is a cytoprotective molecule and major storage form of NO with therapeutic potential for improving multiple domains of physiological dysfunction in CKD. The proposed research will test the efficacy of oral sodium nitrite therapy for improving vascular, motor and cognitive function in patients with CKD.

候选人：Matthew J. Rossman 博士，博士后，接受综合生理学培训 科罗拉多大学（CU）博尔德分校的老龄化研究。在此 K01 申请中，Rossman 博士旨在确定 新型一氧化氮 (NO) 增强化合物亚硝酸钠对于改善血管、运动功能的功效 慢性肾脏病（CKD）患者的（身体）和认知功能。他的近期目标是 获得过渡到独立的校外研究所需的研究培训和专业技能 资助调查员。他的长期目标是建立自己的研究计划，重点是确定 新颖的、基于证据的生活方式和药物干预措施可以预防或延缓疾病的发展 血管、运动和认知功能障碍，以降低 CKD 中 CVD 和其他合并症的风险。职业 发展计划：Rossman 博士的职业发展计划包括：1) 获得新的研究成果 与拟议研究计划相关的技能；2) 肾脏生理学、CKD、运动和认知方面的培训 通过课程作业和与导师团队的会议了解功能、临床试验和生物统计学；；3) 通过课程进行专业技能发展；参加 CU 每周期刊俱乐部/发表演讲 研讨会和全国科学会议；以及与他的导师团队的定期互动。环境： 罗斯曼博士的培训计划的环境将是非常出色的。罗斯曼博士的主要导师博士。 Douglas Seals 和他的合作导师 Michel Chonchol 博士是国际公认的、由 NIH 资助的科学家 在与年龄和年龄有关的转化生物医学研究方面拥有成功指导的良好记录 疾病相关的生理功能障碍和 CKD。 Chonchol 博士也是一名经过委员会认证的肾脏病专家， 科罗拉多大学丹佛分校肾脏疾病和高血压科临床研究主任。咨询 导师 McQueen 博士是 CU Boulder 临床与转化研究中心生物统计学主任 定期为进行临床试验的学员和教师提供指导/咨询。咨询导师Dr. Tamura 是斯坦福大学的副教授，在评估运动和运动方面拥有丰富的经验。 CKD 患者的认知功能。咨询导师 Bryan 博士是亚硝酸盐/NO 生物学方面的专家， 通过补充亚硝酸盐改善生理功能。研究：CKD 是一种非常普遍的疾病 CVD 是 CKD 患者死亡的主要原因。 CKD 中 CVD 风险增加的主要原因 导致血管功能障碍，主要是血管内皮功能障碍和大弹性动脉功能障碍 硬化。运动和认知功能下降在 CKD 中也很常见，并会增加残疾风险 和这些患者的死亡率。血管、运动和认知功能障碍都与 NO 减少有关 生物利用度。亚硝酸盐是一种细胞保护分子，也是 NO 的主要储存形式，具有治疗潜力 改善 CKD 生理功能障碍的多个领域。拟议的研究将测试其功效 口服亚硝酸钠治疗可改善 CKD 患者的血管、运动和认知功能。