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: 10764142
• 负责人: Matthew J Rossman
• 金额: $ 7.56万
• 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/10764142
• 关键词: Biological; Biology; Biomedical Research; Biometry; Blood Vessels; Board Certification; Cardiovascular Diseases; Cause of Death; Child; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Trials; Colorado; Development; Development Plans; Doctor of Philosophy; Elasticity; Environment; Extramural Activities; Functional disorder; Funding; Goals; International; Intervention; Juice; Kidney; Kidney Diseases; Mentored Research Scientist Development Award; Mentors; Mentorship; Motor; Movement; Nitrates; Nitric Oxide; Nitric Oxide Pathway; Nitrites; Patients; Physiological; Physiology; Productivity; Records; Renal Hypertension; Research; Research Assistant; Research Personnel; Research Training; Risk Reduction; Scientist; Sodium Nitrite; Supplementation; Time; Training; United States National Institutes of Health; Universities; Vascular Diseases; Wages; arterial stiffness; cardiovascular disorder risk; career development; cognitive function; comorbidity; disability; disability risk; efficacy testing; improved; innovation; insight; mortality; novel; oral supplementation; preservation; prevent; professor; programs; randomized, clinical trials; seal; skill acquisition; skills; vascular endothelial dysfunction

ABSTRACT AWARDEE: Matthew J. Rossman, Ph.D., is an Assistant Research Professor in the Department of Integrative Physiology at the University of Colorado (CU) Boulder. With his K01 award, Dr. Rossman aims to test the efficacy of daily inorganic nitrate supplementation for improving vascular, motor and cognitive function in patients with chronic kidney disease (CKD). His immediate goal is to obtain the research training and professional skills needed to transition to an independent, extramurally funded investigator. His long-term goal is to establish a research program with a focus on identifying novel interventions that improve vascular, motor and cognitive function to reduce the risk of cardiovascular disease (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; and 3) professional skill development. ENVIRONMENT: The environment for Dr. Rossman’s training plan is 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. Dr. Chonchol is a board-certified nephrologist and Director of Clinical Research in the Division of Renal Diseases and Hypertension at CU Anschutz. Dr. Rossman’s mentorship team also includes experts in biostatistics; motor and cognitive function in patients with CKD; and nitrate/nitrite/NO biology and improving physiological function via nitrate supplementation. RESEARCH: CVD is the leading cause of death in patients with CKD. Increased CVD risk in CKD is largely attributable to 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 CKD. Targeting the nitrate-nitrite-nitric oxide (NO) pathway with inorganic nitrate represents a novel, safe and innovative approach for enhancing NO and improving multiple domains of physiological dysfunction in CKD. Dr. Rossman’s research is testing the efficacy of supplementation with nitrate-rich beetroot juice for improving vascular, motor and cognitive function in patients with CKD in a randomized clinical trial. NEED FOR RESEARCH CONTINUITY SUPPLEMENT: Dr. Rossman is in the final two years of his K01 award and, as such, transitioning to full research independence. Dr. Rossman is expecting a child in January of 2023. To sustain his research productivity and allow Dr. Rossman to devote his time to activities critical for remaining competitive in biomedical research, Dr. Rossman is requesting salary support for a clinical research coordinator for 1 year. The clinical research coordinator will handle key logistical, technical and administrative responsibilities for Dr. Rossman’s K01-supported clinical trial. Dr. Rossman will provide direct oversight of the clinical research coordinator while devoting his time to critical professional development activities.

摘要 获奖者：Matthew J. Rossman博士，是综合系的助理研究教授 生理学在科罗拉多大学（CU）博尔德。凭借K 01奖，罗斯曼博士的目标是测试 每日补充无机硝酸盐对改善老年人血管、运动和认知功能的疗效 慢性肾脏病（CKD）患者。他的近期目标是获得研究培训， 专业技能需要过渡到一个独立的，校外资助的调查。他的长期目标是 是建立一个研究计划，重点是确定新的干预措施，改善血管，运动， 和认知功能，以降低心血管疾病（CVD）和其他CKD合并症的风险。 职业发展计划：罗斯曼博士的职业发展计划包括：1）获得新的 与拟议研究计划相关的研究技能; 2）肾脏生理学、CKD、运动和 认知功能、临床试验和生物统计学;以及3）专业技能发展。 环境：罗斯曼博士的培训计划的环境是杰出的。罗斯曼医生的第一个 导师道格拉斯西尔斯博士和他的共同导师米歇尔Chonchol博士是国际公认的，NIH资助的 具有成功指导记录的科学家。Chonchol医生是一名经过委员会认证的肾病学家， CU Anschutz肾脏疾病和高血压部临床研究主任。博士 罗斯曼的导师团队还包括生物统计学专家;运动和认知功能的患者， CKD;和硝酸盐/亚硝酸盐/NO生物学和通过硝酸盐补充改善生理功能。 研究：CVD是CKD患者死亡的主要原因。CKD中CVD风险增加主要是 归因于血管功能障碍，主要是血管内皮功能障碍和大动脉弹性 硬化运动和认知功能降低在CKD中也很常见，并增加残疾风险 和CKD的死亡率。用无机硝酸盐靶向硝酸盐-亚硝酸盐-一氧化氮（NO）途径代表了一种新的治疗方法。 一种新的、安全的和创新的方法，用于增强NO和改善多个生理领域， CKD中的功能障碍。罗斯曼博士的研究正在测试补充富含硝酸盐的甜菜根的功效 在一项随机临床试验中，果汁用于改善CKD患者的血管、运动和认知功能。 研究持续性的需求：Rossman博士在他的K 01的最后两年 #24453;，并逐步向完全独立的研究方向转变。罗斯曼医生一月份就要生了 2023年。为了维持他的研究生产力，并让罗斯曼博士把他的时间投入到关键活动， 为了保持在生物医学研究领域的竞争力，罗斯曼博士正在为一项临床研究申请工资支持。 一年的协调员。临床研究协调员将处理关键的后勤、技术和行政事务。 Rossman博士的K 01支持的临床试验的责任。罗斯曼博士将直接监督 临床研究协调员，同时致力于关键的专业发展活动。

项目成果

Chronic mitochondria antioxidant treatment in older adults alters the circulating milieu to improve endothelial cell function and mitochondrial oxidative stress.

老年人的慢性线粒体抗氧化治疗可改变循环环境，以改善内皮细胞功能和线粒体氧化应激。

• DOI: 10.1152/ajpheart.00270.2023
• 发表时间: 2023
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Murray,KevinO;Ludwig,KatelynR;Darvish,Sanna;Coppock,McKinleyE;Seals,DouglasR;Rossman,MatthewJ
• 通讯作者: Rossman,MatthewJ