Central Hub for Kidney Precision Medicine

摘要 现代生物医学研究面临的一个主要挑战是相对无法翻译 科学发现转化为重大治疗突破的速度越来越快。这一缺点 在肾脏疾病中尤其引人注目， 发表在肾脏病学上的文章比所有其他内科专业都少。慢性肾脏 慢性肾脏病（CKD）是一个影响美国2000多万人的公共卫生问题， 除了已证明能减缓CKD进展的肾素-血管紧张素系统抑制剂之外， 降低死亡率，或者提高生活质量。急性肾损伤（阿基）影响高达10%的 美国的住院患者，并与死亡率，住院时间延长， 以及随后CKD的发展或进展。目前没有公认的治疗方法， 预防或改善阿基过程的方法迫切需要帮助 定义CKD和阿基疾病亚组，并确定关键细胞、途径和新的治疗靶点。 治疗我们建议建立一个多尺度的了解CKD和阿基，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。我们计划建立肾脏精密 医药项目中心枢纽，由经验丰富， 多学科团队，具有良好的成功记录。本报告的总体目标 KPMP的中央枢纽应用程序是为了创造一个环境，以促进科学的严谨性，病人 安全，以及成功的跨学科团队科学，这是导致重大进展所必需的， 肾病研究。为了实现这一目标，我们组建了一个拥有以下专业知识的团队： 数据协调中心管理、编程、生物统计学、生物医学信息学，以及 流行病学，拥有超过25年的经验，协调非常成功的大规模 纵向研究。我们的调查团队在建立全球肾脏疾病 研究生态系统，并率先发展了团队科学结构，以推进 肾小球疾病的精准医疗方法。我们已经证明了我们的能力：1）收集， 管理、汇总并确保所有KPMP数据和样本的质量控制，2）协调存储 所有KPMP数据和样本的分发，3）促进数据分析和可视化，4） 建立肾脏组织图谱，5）提供行政支持，建立必要的工作机制 小组，6）征求病人的意见和反馈，7）开发和管理一个网站，供内部和 外部沟通、分析和发现，以及8）管理资金机会池， 建立新的伙伴关系。

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.