Delineating the kidney brain axis in children with severe malaria (KID-BRAIN)

项目摘要/摘要 这一职业奖项的总体目标是将巴特博士打造成一名独立资助的内科科学家。 改善急性肾损伤(AKI)儿童的存活率，并确定将使 让孩子们茁壮成长。巴特博士将描述重症肾病儿童肾脏相关脑损伤的机制 疟疾。巴特博士是Makerere大学卫生学院的讲师和儿科肾病专家 科学。从他过去的研究工作中，他建立了基于证据的AKI诊断方法 和表型特征。他探索了护理点测试在评估AKI中的效用，并 重症疟疾AKI与非疟疾发热相关AKI演示的力学比较 血管内皮细胞激活和免疫激活的差异。他还评估了脑损伤和 急性营养不良和镰状细胞性贫血后急性KI患儿的神经学转归。他有 发表了一篇特邀综述，强调了儿童AKI的诊断和管理方面的挑战 概述了未来研究的优先事项，其中包括以下详细的神经发育评估 Aki用于患有严重疟疾的儿童。巴特博士将把75%的保护时间用于未来5年的工作 与他的导师一起了解脑肾相声的剧烈变化如何转化为长期损伤 并确定可修改的途径，以促进肾脏和大脑的适应性 严重疟疾后的康复。巴特博士在过去的基础上制定了一项教育计划 培训和解决研究培训缺口，一旦填补，将提供基础，推动他进入 独立研究生涯。这款K43将围绕神经行为方面的专门培训进行构建 评估以及生物标志物测试和解释。它将帮助巴特博士实现他的目标 它们是：(1)确定AKI表型与脑损伤的生物特征相关联的程度 和恢复(2)确定AKI和AKI表型与脑水肿相关的程度(3) 明确神经行为结局、脑损伤生物标志物和AKI表型之间的联系。博士 巴特将在肾脏和大脑生物标记物测试和解释方面获得一系列技能，在大脑方面 影像解释、数据分析和进行纵向研究，以及神经行为评估 孩子们。预计在完成这项裁决时，利用已开发的专门知识和产生的数据， 他将阐明严重疟疾中肾-脑串扰的可修改通路，为 R01的应用和未来干预研究的平台，以预防损伤，促进脑和 严重疟疾后的肾脏恢复。

Project summary/ abstract The overall goal of this career award is to build Dr Batte into an independently funded physician scientist improving survival of children with acute kidney injury (AKI) and identify interventions that will enable children to thrive. Dr Batte will delineate mechanisms of kidney-related brain injury in children with severe malaria. Dr Batte is a Lecturer and a Pediatric nephrologist at Makerere University college of health sciences. From his past research work, he has established evidence-based approaches to AKI diagnosis and phenotypic characterization. He has explored the utility of point-of-care tests in evaluating AKI, and has mechanistically compared severe malaria AKI and non-malaria febrile illnesses related AKI demonstrating differences in endothelial activation and immune activation. He has also evaluated brain injury and neurological outcomes of children with AKI following acute malnutrition and sickle cell anemia. He has published an invited review highlighting challenges in the diagnosis and management of AKI in children and outlined priorities for future research, which included detailed neuro-developmental assessments following AKI in children with severe malaria. Dr Batte will use the 75% protected time for the next 5 years working with his mentors to understand how acute changes in brain-kidney crosstalk translate to long-term injury and to identify modifiable pathways amenable to intervention to promote adaptive kidney and brain recovery following severe malaria. Dr Batte has developed an educational plan that builds on his past training and addresses research training gaps, that once filled will provide the basis to propel him into an independent research career. This K43 will be structured around specialized training in neurobehavioral evaluation along with biomarker testing and interpretation. It will help Dr Batte to achieve his objectives which are to; (1) determine the extent that AKI phenotypes are associated with biosignatures of brain injury and recovery (2) establish the extent that AKI and AKI phenotypes are associated with cerebral edema (3) define the association between neurobehavioral outcomes, brain injury biomarkers and AKI phenotypes. Dr Batte will attain a number of skill-sets in kidney and brain biomarker testing and interpretation, skills in brain imaging interpretation, data analysis and conduct of longitudinal studies, and neurobehavioral evaluation of children. It is expected that at completion of this award, with the developed expertise and data generated, he will elucidate modifiable pathways of kidney-brain cross talk in severe malaria, setting the stage for an R01 application and a platform for future intervention studies to prevent injury and promote brain and kidney recovery following severe malaria.