Central Hub for Kidney Precision Medicine

摘要 现代生物医学研究的一个主要挑战是相对无法将 提高科学发现转化为重大治疗突破的速度。这一缺点有 在肾脏疾病中尤其引人注目，在那里随机临床试验的数量 在肾脏病学上发表的论文比所有其他内科专科都要少。慢性肾脏 疾病(CKD)是一个公共健康问题，在美国有2000多万人受到影响，几乎没有药物 除了肾素-血管紧张素系统的抑制剂外，其他药物已被证明可以减缓CKD的进展， 降低死亡率，或提高生活质量。急性肾损伤(AKI)影响高达10%的 在美国住院的患者，并与死亡率、住院时间延长、 以及CKD的后续发展或进展。目前还没有公认的治疗方法 预防或改善AKI病程的方法迫切需要帮助 定义CKD和AKI疾病亚组并确定关键细胞、途径和靶点 治疗。我们建议建立对CKD和AKI的多尺度理解，通过整合 肾脏疾病进展的细胞和器官水平特征的临床数据包括 疾病的基因组和表观基因组驱动因素的询问。我们计划建造肾脏精密 在强大的现有基础设施上，由经验丰富的 多学科团队，具有良好的成功记录。这样做的首要目标是 KPMP的中心中心应用是为了创造一个环境来促进科学严谨、患者 安全，以及取得重大进展所必需的成功的跨学科团队科学 肾脏疾病研究。为了实现这一目标，我们组建了一支具有以下专业知识的团队 数据协调中心管理、编程、生物统计、生物医学信息学和 流行病学，有超过25年的经验协调非常成功的大规模 纵向研究。我们的调查团队帮助建立了一个全球肾脏 研究生态系统，并率先开发了团队科学结构，以推动 肾小球疾病的精准医学方法。我们已经证明了我们有能力收集、 管理、汇总和确保所有KPMP数据和样本的质量控制，2)协调存储 和分发所有KPMP数据和样本，3)促进数据分析和可视化，4) 创建肾组织图谱，5)提供行政支持并建立必要的工作 小组，6)征求患者意见和反馈，7)开发和管理内部和 外部沟通、分析和发现，以及管理机会资金池，以 建立新的合作伙伴关系。

ABSTRACT A major challenge for modern biomedical research has been the relative inability to translate the increasing rate of scientific discovery into major therapeutic breakthroughs. This shortcoming has been particularly dramatic in kidney diseases, where the number of randomized clinical trials published in nephrology is fewer than all other specialties of internal medicine. chronic kidney disease (CKD) is a public health problem affecting more than 20 million people in the US, few drugs other than inhibitors of the renin-angiotensin system have been proven to slow CKD progression, lower mortality rates, or improve quality of life. Acute kidney injury (AKI) affects up to 10% of all hospitalized patients in the US, and is associated with mortality, prolonged hospital length of stay, and subsequent development or progression of CKD. Currently there is no accepted therapeutic approach to either prevention or amelioration of the course of AKI There is a critical need to help define CKD and AKI disease subgroups and identify critical cells, pathways and targets for novel therapies. We propose to establish a multiscale understanding of CKD and AKI, by integrating clinical data with the cell and organ level features of kidney disease progression including interrogation of genomic and epigenomic drivers of disease. We plan to build the Kidney Precision Medicine Project Central Hub on strong existing infrastructure led by a highly experienced, multidisciplinary team with a strong track record of success. The overarching objective of this Central Hub application for the KPMP is to create an environment to promote scientific rigor, patient safety, and the successful interdisciplinary team science necessary to result in major advances in kidney disease research. In order to accomplish this, we have assembled a team with expertise in data coordinating center management, programming, biostatistics, biomedical informatics, and epidemiology, with over 25 years of experience coordinating highly successful large-scale longitudinal research studies. Our investigative team was instrumental in establishing a global renal research ecosystem, and has pioneered development of a team science structure to advance a precision medicine approach to glomerular diseases. We have demonstrated our ability to 1) collect, curate, aggregate and ensure quality control of all KPMP data and samples, 2) coordinate storage and distribution of all KPMP data and samples, 3) facilitate data analyses and visualization, 4) create a kidney tissue atlas, 5) provide administrative support and establish necessary working groups, 6) solicit patient input and feedback, 7) develop and manage a website for internal and external communication, analysis and discovery, and 8) administer an Opportunity Pool of funds to form new partnerships.