Non Invasive Assessment of Microcirculation Function and Kidney Disease

微循环功能与肾脏疾病的无创评估

• 批准号: 10437477
• 负责人: Rakesh Malhotra
• 金额: $ 19.45万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10437477
• 关键词: Acute; Affect; Albuminuria; Assessment tool; Basement membrane; Blood Vessels; Blood capillaries; California; Cardiovascular Diseases; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Diabetes Mellitus; Dietary Proteins; Disease Progression; Doctor of Philosophy; Educational workshop; End stage renal failure; Enrollment; Future; Gender; Glomerular Filtration Rate; Glucose; Hemorrhage; Histology; Histopathology; Hyperemia; Hypertension; Individual; Intervention Studies; Kidney; Kidney Diseases; Laser-Doppler Flowmetry; Lasers; Lead; Learning; Measurement; Measures; Mentors; Mentorship; Methods; Microcirculation; Microscopic Angioscopy; Microvascular Dysfunction; Monitor; Nephrectomy; Operative Surgical Procedures; Oral; Outcome; Pathogenesis; Pathogenicity; Pathologic; Pathologist; Patients; Peripheral; Persons; Pharmaceutical Preparations; Phase; Physiological; Play; Population; Prognosis; Proteins; Renal carcinoma; Renal function; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Skin; Statistical Methods; Stimulus; Structure of glomerular mesangium; Techniques; Technology; Time; Tissues; Titrations; Training; Translations; Universities; Urologist; boys; career; cigarette smoking; clinical predictors; clinical risk; density; design; disease prognosis; experience; follow-up; glomerulosclerosis; health assessment; hemodynamics; high risk; human old age (65+); improved; insight; kidney biopsy; male; minimally invasive; multidisciplinary; non-invasive monitor; novel; patient oriented research; programs; rate of change; recruit; response; skills; treatment response

PROJECT SUMMARY This is a submission of a K23 application by Dr. Rakesh Malhotra, MD, MPH, a nephrologist at University of California San Diego (UCSD). Through this proposal Dr. Malhotra intends to establish himself as an independent investigator studying non-invasive microvascular measurements in chronic kidney disease (CKD). Candidate: Dr. Malhotra’s training objectives include; 1) to become proficient in the measurement of non- invasive microvascular techniques and translation to patient-oriented research; 2) to gain expertise in advanced statistical methods relevant to clinical trials; and 3) to learn the necessary skills to develop an independent research program and to design and lead clinical trials. Dr. Malhotra will accomplish these objectives through mentorship, coursework, and participation in workshops. He has assembled a multidisciplinary team of scientists including Dr. Joachim Ix, an expert clinical trialist (primary mentor), Dr. Boy Houben, a leader in the field of microcirculation (co-mentor); Dr. Matthew Allison, a leader in the field of vascular health and assessment (co-mentor) and Dr. Florin Vaida, a PhD level biostatistician (statistical co- mentor). In addition, Dr. Haiyan Zhang a renal pathologist with experience in nephropathology and Dr. Ithaar Derweesh a urologist with expertise in minimally invasive surgery will participate as a consultant without pay. Research: Renal microcirculation plays an important role in the pathogenesis of CKD. The kidney biopsy is the standard technique to assess abnormalities in renal microvasculature, but is invasive and rarely done. Dr. Malhotra’s overall hypothesis is that the non-invasive microvascular measurements may improve our understanding of the renal microcirculation, and improve our ability to identify those at risk of kidney disease progression. In Aim 1, Dr. Malhotra will evaluate the relationship between non-invasive microvascular measurements (skin capillary density and % recruitment (by capillaroscopy) and heat-induced skin %- hyperemia (by laser Doppler)) with glomerular sclerosis among 100 individuals with CKD undergoing kidney biopsy and 50 persons with CKD undergoing nephrectomy for suspected kidney cancer. In Aim 2a, Dr. Malhotra will evaluate the association of clinical risk factors with microvascular dysfunction as assessed with capillaroscopy and laser Doppler among 200 CKD subjects. In Aim 2b, Dr. Malhotra will determine the associations between skin microvascular function and longitudinal changes in kidney function in the 200 CKD subjects. Lastly, in Aim 3, Dr. Malhotra will evaluate whether acute changes in % capillary recruitment in response to a dietary protein load is correlated with concurrent changes in eGFR, as measure of RFR in 20 CKD subjects. Both the training and research plans will lay the groundwork for use of non-invasive microvascular techniques in clinical trials to allow assessment of renal hemodynamics and monitor responses to therapies and clinical outcomes in the next and independent phase of Dr. Malhotra’s career.

项目总结 这是肾病学家Rakesh Malhotra博士提交的K23申请，医学博士，公共卫生硕士，在 加州大学圣地亚哥分校(UCSD)。通过这项提议，马尔霍特拉博士打算将自己确立为 研究慢性肾脏疾病非侵入性微血管测量的独立研究人员 (CKD)。 应聘者：马尔霍特拉博士的培训目标包括：1)熟练掌握非 侵入性微血管技术和转化为以患者为中心的研究；2)获得专业知识 与临床试验相关的先进统计方法；以及3)学习必要的技能，以制定 独立研究计划，并设计和领导临床试验。马尔霍特拉博士将实现这些目标 通过指导、课程作业和参加研讨会来实现目标。他已经组建了一支 多学科科学家团队，包括临床试验专家约阿希姆九世博士(主要导师)、博伊博士 胡本，微循环领域的领导者(共同导师)；Matthew Allison博士，微循环领域的领导者 血管健康和评估(共同导师)和弗洛林·瓦伊达博士，博士级别的生物统计学家(统计联合 导师)。此外，具有肾脏病理经验的肾脏病理学家张海燕博士和伊萨尔博士 拥有微创手术专业知识的泌尿科医生德韦什将以顾问的身份参加，但不支付报酬。 研究：肾微循环在CKD发病机制中起重要作用。肾活检是 这是评估肾微血管异常的标准技术，但具有侵入性且很少使用。Dr。 Malhotra的总体假设是，无创微血管测量可能会改善我们的 了解肾脏微循环，并提高我们识别肾脏疾病风险的能力 进步。在目标1中，Malhotra博士将评估非侵入性微血管与 测量(皮肤毛细血管密度和募集率(通过毛细管镜)和热诱导皮肤%- 100例慢性肾脏病患者肾脏充血(激光多普勒)伴肾小球硬化 活检和50例慢性肾脏病患者因疑似肾癌而接受肾切除术。在Aim 2a中，Dr。 Malhotra将评估临床危险因素与微血管功能障碍的关系，评估方法为 200例慢性肾脏病患者毛细支气管镜和激光多普勒检查结果分析在Aim 2b中，Malhotra博士将确定 200例慢性肾脏病患者皮肤微血管功能与肾功能纵向变化的关系 研究对象。最后，在目标3中，Malhotra博士将评估毛细血管重新充盈率的急剧变化 对饮食蛋白质负荷的反应与EGFR的同步变化相关，作为20例RFR的衡量标准 CKD受试者。培训和研究计划都将为使用非侵入性 用于评估肾脏血流动力学和监测反应的临床试验中的微血管技术 马尔霍特拉博士职业生涯的下一个独立阶段的治疗和临床结果。