Determinants of chronic kidney disease in African-American live kidney donors

非裔美国活体肾捐献者慢性肾病的决定因素

• 批准号: 9144380
• 负责人: Allan B Massie
• 金额: $ 15.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9144380
• 关键词: Accounting; Advisory Committees; African American; Age; Ancillary Study; Biological; Biology; Biometry; Caring; Caucasians; Cessation of life; Chronic Kidney Failure; Clinical Research; Cohort Studies; Collection; Communities; Complex; Counseling; Data; Decision Making; Doctor of Philosophy; Donor Selection; End stage renal failure; Epidemiologist; Epidemiology; Etiology; Evaluation; Female; Foundations; Friends; Funding; Gender; General Population; Genes; Genetic; Genetic Determinism; Genotype; Goals; Health; Hypertrophy; Individual; Informed Consent; Interview; Investigation; Kidney; Kidney Diseases; Knowledge; Lead; Leadership; Life; Light; Living Donors; Measurement; Medical; Medical Records; Mentored Research Scientist Development Award; Mentors; Modeling; Nephrectomy; Nephrology; Obesity; Operative Surgical Procedures; Organ Donor; Outcome; Parents; Participant; Patients; Physicians; Physiology; Population; Prevention; Prospective Studies; Recruitment Activity; Research; Research Design; Research Proposals; Risk; Risk Factors; Saliva; Sampling; Specimen; Subgroup; Testing; Time; Training; Transplant Recipients; Transplant Surgeon; Transplantation; United States; United States National Institutes of Health; Variant; Visit; abstracting; age related; cardiovascular disorder epidemiology; career; caucasian American; clinical decision-making; cohort; design; disorder risk; epidemiology study; experience; follow-up; genetic epidemiology; high risk; improved; novel; patient oriented research; patient safety; professor; programs; prospective; risk variant

 DESCRIPTION (provided by applicant): Allan B. Massie, PhD, is an Assistant Professor of Surgery and Epidemiology at Johns Hopkins. He seeks a Mentored Research Scientist Development Award in order to gain training and experience in nephrology, genetic epidemiology, and the conduct of cohort studies and to transition to independent research. Every year, 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a relative, friend, or stranger with end-stage renal disease (ESRD). The largest cohort study of kidney donors to date - the foundation of the conventional wisdom that "live kidney donation is safe" - involved a > 99% Caucasian population. However, African-American (AA) donors are at elevated risk of post-donation ESRD and death compared to Caucasians. Unfortunately, risk prediction in this critically important population is poor, hampering donor screening and informed consent, depriving AA kidney donors of accurate information about their personal risk after kidney donation, and limiting opportunities to mitigate long-term risk in this population. The proposed research is nested within an ongoing, NIH-funded multicenter cohort study of AA donors. The aims of the project are: 1) to identify the association between high-risk variants of the APOL1 gene and CKD following donation in AA live kidney donors; 2) to identify risk factors for long-term eGFR decline in AA kidney donors; and 3) to compare post-donation eGFR trajectories in AA donors to those in AA nondonors. Aim 1 will implement a nested case-cohort study within the parent study; Aim 2 will draw on donor medical records obtained via the parent study; and Aim 3 will compare eGFR calculated from medical records of the parent study to data from the ARIC and CARDIA cohorts. The proposed research leverages a large cohort of AA donors, but is distinct from the parent study in its study design, novel collection of biologica specimens to understand genetic determinants, and novel collection of longitudinal data to study eGFR trajectories. The research proposal outlines a detailed proposal to give Dr. Massie the training required to complete the research, under the leadership of mentor Dr. Dorry Segev MD PhD and Dr. Josef Coresh MD PhD, drawing from the advice of an advisory team that includes experts in nephrology, genetic epidemiology, study design, and biostatistics. Dr. Segev is a transplant surgeon, Director of Clinical Research in the Division of Transplantation at Johns Hopkins, and PI of the parent study for the proposed research. Dr. Coresh is an epidemiologist, Director of the Cardiovascular Epidemiology Program at Johns Hopkins and leader of the Chronic Kidney Disease Consortium. Dr. Massie hopes eventually to lead independent research programs investigating long-term outcomes of transplant recipients and live organ donors. Completion of the proposed aims will improve risk prediction for AA live kidney donors and prospective donors, aid in medical decision-making, enhance informed consent, and provide vital information relevant to the long-term health outcomes of the 14,000 AA live kidney donors living in the United States.

 描述（由申请人提供）：Allan B。Massie博士是约翰霍普金斯大学外科和流行病学助理教授。他寻求指导研究科学家发展奖，以获得肾脏病学，遗传流行病学和队列研究的开展方面的培训和经验，并过渡到独立研究。在美国，每年有6000名健康人接受活体供肾切除术，以使患有终末期肾病（ESRD）的亲属，朋友或陌生人受益。迄今为止最大的肾脏捐献者队列研究-传统智慧的基础，“活体肾脏捐献是安全的”-涉及> 99%的白人人群。然而，与白人相比，非洲裔美国人（AA）捐赠者的捐赠后ESRD和死亡风险较高。不幸的是，这一至关重要的人群的风险预测很差，阻碍了供体筛选和知情同意，剥夺了AA肾脏供体关于其肾脏捐献后个人风险的准确信息，并限制了减轻这一人群长期风险的机会。拟议的研究是嵌套在一个正在进行的，NIH资助的AA捐助者的多中心队列研究。该项目的目的是：1）确定AA活体肾脏供体中APOL 1基因的高风险变体与捐赠后CKD之间的关联; 2）确定AA肾脏供体中长期eGFR下降的风险因素;和3）比较AA供体与AA非供体的捐赠后eGFR轨迹。目标1将在母研究中实施嵌套病例队列研究;目标2将利用通过母研究获得的供体病历;目标3将比较根据母研究病历计算的eGFR与ARIC和CARDIA队列的数据。拟议的研究利用了一个大型AA供体队列，但在研究设计、新的生物学标本收集以了解遗传决定因素以及新的纵向数据收集以研究eGFR轨迹方面与母研究不同。研究提案概述了一项详细的提案，在导师Dorry Segev MD PhD和Josef Coresh MD PhD博士的领导下，为Massie博士提供完成研究所需的培训，并听取了包括肾脏病学，遗传流行病学，研究设计和生物统计学专家在内的咨询团队的建议。Segev博士是一名移植外科医生，约翰霍普金斯移植部临床研究主任，也是拟议研究的母研究的PI。Coresh博士是一位流行病学家，约翰霍普金斯大学心血管流行病学项目主任，慢性肾脏病联盟的领导人。Massie博士希望最终能够领导独立的研究项目，调查移植受体和活体器官捐赠者的长期结果。拟议目标的完成将改善AA活体肾脏捐献者和潜在捐献者的风险预测，帮助医疗决策，增强知情同意，并提供与生活在美国的14，000名AA活体肾脏捐献者的长期健康结果相关的重要信息。