Racial/Ethnic Disparities in Kidney Function Decline: Genes or Environment?

项目概述：这是为卡门·A·佩拉尔塔博士申请K23奖的申请，他提出了一部小说， 多学科方法了解肾功能下降的种族/民族差异。本奖项 将使佩拉尔塔博士拥有资源和受保护的时间来实现以下职业发展目标：(1) 成为肾脏种族/民族差异领域的独立、翻译临床研究人员 (2)成为应用遗传流行病学方法研究这些疾病的专家 差异；以及(3)利用社会人口学测量来提高对复合体的理解 造成这些差异的机制。为了实现这些目标，佩拉尔塔博士组织了一项指导 她的团队由她的赞助商和主要导师Michael Shlipak博士(该领域的专家 早期肾功能障碍的心血管并发症)和两位共同导师：Neil Risch博士(遗传病 流行病学家)和Paula Braveman博士(健康的社会决定因素专家)。 肾脏疾病的流行目前影响着13%的美国成年人，并进展到末期 肾脏疾病(ESRD)对少数群体的影响各不相同。非洲裔美国人和西班牙裔美国人增长最快- ESRD人群中的ING组。尽管在晚期肾脏的进展中有很好的记录差异 从疾病到终末期肾病，还没有研究评估慢性肾脏疾病(CKD)或早期肾脏的发病率 在美国，跨种族/民族的功能衰退。目前尚不清楚某些种族/民族是否 由于共同的遗传祖先或社会或环境原因，遗传易感性增加- 心理因素解释了观察到的差异。使用动脉粥样硬化的多种族研究数据 (MESA)，佩拉尔塔博士将比较四个主要种族的肾功能减退率和CKD发生率 并测试可能的遗传和社会人口机制来解释这些差异。三 提出了具体目标：目标1：比较肾功能减退率和慢性肾脏发生率 疾病横跨四个主要种族/民族(高加索人、非裔美国人、拉美裔和中国人- 美国人)使用基于肌酐和胱抑素C的测量方法；目标2：评估遗传祖先是否 在种族群体中肾功能下降和慢性肾脏疾病发生的独立预测因素 探讨基因-环境相互作用在肾功能减退和肾脏发病中的作用；目的3： 评估个人和邻里层面的社会经济特征与肾脏的关系 不同种族之间的功能衰退和肾脏疾病的发生率。 相关性：更好地理解肾功能种族/民族差异的机制 肾功能不全早期的下降可能导致重要的干预和预防策略 在阻止这场代价高昂的流行病方面。。

Project Summary: This is an application for a K23 award for Dr. Carmen A. Peralta, who proposes a novel, multi-disciplinary approach to understanding racial/ethcnic disparities in kidney function decline. This award will allow Dr. Peralta the resources and protected time to achieve the following career development goals: (1) to become an independent, translational clinical researcher in the field of racial/ethnic disparities in kidney disease; (2) to become an expert in the application of genetic epidemiology methods to study these differences; and (3) to utilize sociodemographic measurements to improve understanding of the complex mechanisms involved in these disparities. To achieve these goals, Dr. Peralta has assembled a mentoring team comprised of her sponsor and primary mentor, Dr. Michael Shlipak (an expert in the field of cardiovascular complications of early kidney dysfunction), and two co-mentors: Dr. Neil Risch (a genetic epidemiologist) and Dr. Paula Braveman (an expert in social determinants of health). The epidemic of kidney disease currently affects 13% of U.S. adults, and the progression to end stage renal disease (ESRD) affects minorities disparately. African-Americans and Hispanics are the fastest grow- ing groups in the ESRD population. Despite well-documented disparities in progression of advanced kidney disease to ESRD, no studies have evaluated the incidence of chronic kidney disease (CKD) or early kidney function decline in the US across racial/ethnic groups. It is unknown whether certain racial/ethnic groups have an increased genetic predisposition due to a common genetic ancestry or whether social or environ- mental factors explain observed differences. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), Dr. Peralta will compare rates of kidney function decline and incident CKD across four major racial groups and test possible genetic and sociodemographic mechanisms to explain these differences. Three specific aims are proposed: Aim 1: To compare rates of kidney function decline and incident chronic kidney disease across four major racial/ethnic groups (Caucasians, African-Americans, Hispanics, and Chinese- Americans) using creatinine and cystatin C based measures; Aim 2: To evaluate whether genetic ancestry is an independent predictor of kidney function decline and incident chronic kidney disease within racial groups and to explore gene-environment interactions in kidney function decline and incident kidney; and Aim 3: To evaluate the association of individual and neighborhood-level socioeconomic characteristics with kidney function decline and incident kidney disease across racial groups. Relevance: A better understanding of the mechanisms involved in racial/ethnic disparities in kidney function decline at earlier stages of kidney dysfunction could lead to important interventions and prevention strategies in halting this costly epidemic. .