Cardiovascular Disease in Children with Chronic Kidney Disease

慢性肾病儿童的心血管疾病

• 批准号: 8027221
• 负责人: MARK M. MITSNEFES
• 金额: $ 16.97万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8027221
• 关键词: Accounting; Acute; Adenosine Triphosphate; Adult; Area; Arrhythmia; Award; Biological Markers; Biological Markers; Cardiac; Cardiomyopathies; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Child; Childhood; Chronic Kidney Failure; Clinical; Clinical Research; Clinical Sciences; Clinical Trials Design; Congenital Heart Defects; Coronary Vessels; Death Rate; Development; Dialysis procedure; Disease; EFRAC; Energy Metabolism; Epidemiologic Studies; Ethics; Faculty; Fibrosis; Frequencies; Functional disorder; Funding; Goals; Grant; Heart; Heart Atrium; Heart Diseases; Heart Hypertrophy; Hypertrophic Cardiomyopathy; Hypertrophy; Intervention; Ischemia; Kidney Transplantation; Left; Left Ventricular Hypertrophy; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Manuscripts; Master of Science; Measurement; Medial; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolism; Methodology; Microscopic; Midcareer Investigator Award in Patient-Oriented Research; Mitral Valve Insufficiency; Morbidity - disease rate; Muscle; Myocardial; Myocardial dysfunction; Myocardium; Nephrology; Patients; Pediatric Hospitals; Peer Review; Phosphocreatine; Physiology; Postdoctoral Individual National Research Service Award; Prevention program; Property; Renal Replacement Therapy; Research; Research Methodology; Research Personnel; Research Project Grants; Resources; Restrictive Cardiomyopathy; Role; SECTM1 gene; Scientist; Secondary to; Severities; Sudden Death; Techniques; Technology; Time; Training; Training Programs; Translational Research; United States National Institutes of Health; Universities; Ventricular; Work; Writing; adipokines; adiponectin; base; career; design; experience; innovation; interest; mortality; patient oriented research; pressure; prevent; programs; sudden cardiac death; translational study; young adult

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in children and young adults with chronic kidney disease (CKD). The applicant's long-term career goal is to define biologic targets for interventions to prevent and slow progression of CVD in children with CKD through advancing Patient-Oriented Research (POR). Since early years of his career, the applicant's research has been focusing on elucidating the mechanisms of cardiovascular abnormalities in children with CKD through epidemiological and translational studies. He has maintained continuous funding at the federal level in this area of research. He currently has an R01 examining the role of adiponectin and other adipokines in the development of cardiovascular abnormalities in children with CKD. Dr. Mitsnefes is also a Co-investigator and a Co-Chair of the Cardiovascular Committee for the NIH funded CKiD study (U01 mechanism), a multicenter effort designed to study children with CKD. The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to study CVD in children with CKD. Specific aims of this award are: 1) further the candidate's own research and 2) mentor junior faculty and fellows who are pursuing POR in pediatric nephrology. The first aim will be based and build upon candidate's previous research and will examine early biological markers of myocardial dysfunction in children on maintenance dialysis and after kidney transplantation: 1) left ventricular myocardial circumferential strain (Ecc), and 2) muscle energy metabolism by 31Phosphorus Magnetic Resonance Spectroscopy (31P MRS), and 3) left atrial size and markers of diastolic function. The second aim is based upon applicant's previous mentoring experience: since 2003 Dr. Mitsnefes has mentored 8 research fellows, and has been senior author on 17 peer-reviewed articles with his mentee as the first author. The Mentoring Plan for early career faculty and research fellows will incorporate the existing T32, K12 and K30 training programs at Cincinnati Children's Hospital Medical Center to produce outstanding clinical scientists who go on to be independent investigators. It will consist of: 1) individualized mentoring of 2 junior faculty who are planning to apply for K23 awards; 2) intensive practical training in patient-oriented research within the context of the current research projects of candidate's R01 for 2 fellows as well as development of their own independent research projects (F32 award); 3) course work in fulfillment of Master's of Science degree in the Graduate Program in Clinical and Translational Research at the University of Cincinnati; 4) participation of fellows in established other didactic programs on manuscript and grant writing, design of clinical trials and clinical research methodology, and ethics in clinical research. Cincinnati Children's Hospital Medical Center provides an ideal setting for this award because of the commitment to POR and ongoing initiatives to promote innovative clinical research through the presence of a strong Center for Clinical and Translational Science and Training. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the major cause of death in children and young adults with chronic kidney disease (CKD). the mechanisms of cardiovascular disease (CVD) in children with chronic kidney disease (CKD). The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to better understand the mechanisms of heart problems in children on dialysis and with kidney transplant. This goal will be achieved by expansion of candidate's own research through using MRI technology to study early heart abnormalities, and by mentoring young investigators who are interested in studying heart problems in children with CKD. By understanding the cause of heart abnormalities, we hope to develop the program for prevention or treatment of this problem in children with CKD.

描述（由申请人提供）：心血管疾病（CVD）是慢性肾病（CKD）儿童和年轻人发病和死亡的主要原因。申请人的长期职业目标是通过推进以患者为导向的研究（POR）来确定干预措施的生物学目标，以预防和减缓 CKD 儿童 CVD 的进展。自职业生涯早期以来，申请人的研究一直致力于通过流行病学和转化研究阐明 CKD 儿童心血管异常的机制。他在这一研究领域一直获得联邦层面的持续资助。他目前正在进行一项 R01 研究，研究脂联素和其他脂肪因子在 CKD 儿童心血管异常发展中的作用。 Mitsnefes 博士还是 NIH 资助的 CKiD 研究（U01 机制）心血管委员会的联合研究员和联合主席，该研究是一项旨在研究 CKD 儿童的多中心项目。该 K24 计划的目的是为候选人提供受保护的时间和资源，以建立一个综合计划来研究 CKD 儿童的 CVD。该奖项的具体目标是：1) 进一步推进候选人自己的研究，2) 指导在儿科肾病学领域从事 POR 研究的初级教员和研究员。第一个目标将基于候选人之前的研究，并将检查维持性透析和肾移植后儿童心肌功能障碍的早期生物标志物：1) 左心室心肌圆周应变 (Ecc)，2) 通过 31 磷磁共振波谱 (31P MRS) 检测肌肉能量代谢，3) 左心房大小和舒张功能标志物。第二个目标是基于申请人之前的指导经验：自2003年以来，Mitsnefes博士已经指导了8名研究员，并以他的导师为第一作者，成为17篇同行评审文章的资深作者。针对早期职业教师和研究员的指导计划将纳入辛辛那提儿童医院医疗中心现有的 T32、K12 和 K30 培训计划，以培养未来成为独立研究人员的杰出临床科学家。它将包括： 1) 对 2 名计划申请 K23 奖项的初级教师进行个性化指导； 2）在候选人R01当前研究项目的背景下，对2名研究员进行以患者为导向的研究的强化实践培训，以及开发自己的独立研究项目（F32奖）； 3）完成辛辛那提大学临床和转化研究研究生课程理学硕士学位的课程工作； 4) 研究员参与已建立的其他教学项目，内容涉及手稿和拨款写作、临床试验设计和临床研究方法以及临床研究伦理。辛辛那提儿童医院医疗中心为该奖项提供了理想的环境，因为它致力于 POR 并通过强大的临床和转化科学与培训中心不断开展促进创新临床研究的举措。 公共卫生相关性：心血管疾病 (CVD) 是患有慢性肾病 (CKD) 的儿童和年轻人死亡的主要原因。慢性肾病（CKD）儿童心血管疾病（CVD）的机制。该 K24 计划的目的是为候选人提供受保护的时间和资源，以建立一个全面的计划，以更好地了解接受透析和肾移植的儿童的心脏问题机制。这一目标将通过使用 MRI 技术研究早期心脏异常来扩展候选人自己的研究，并指导对研究 CKD 儿童心脏问题感兴趣的年轻研究人员来实现。通过了解心脏异常的原因，我们希望制定预防或治疗 CKD 儿童这一问题的计划。