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

描述（由申请人提供）： 这是卡门·A博士的K23奖申请书Peralta提出了一种新颖的多学科方法来理解肾功能下降的种族/民族差异。该奖项将使Peralta博士获得资源和保护时间，以实现以下职业发展目标：（1）成为肾脏疾病种族/民族差异领域的独立，转化临床研究人员;（2）成为应用遗传流行病学方法研究这些差异的专家;以及（3）利用社会人口学测量来提高对这些差异所涉及的复杂机制的理解。为了实现这些目标，Peralta博士组建了一个指导团队，由她的赞助商和主要导师Michael Shlipak博士（早期肾功能不全心血管并发症领域的专家）和两位共同导师：Neil Risch博士（遗传流行病学家）和Paula Braveman博士（健康社会决定因素专家）组成。肾脏疾病的流行目前影响着13%的美国成年人，并且进展为终末期肾脏疾病（ESRD）严重影响少数民族。非洲裔美国人和西班牙裔美国人是ESRD人群中增长最快的群体。尽管晚期肾脏疾病进展为ESRD的差异有充分的记录，但没有研究评估美国不同种族/族裔组的慢性肾脏疾病（CKD）或早期肾功能下降的发生率。尚不清楚某些种族/民族群体是否由于共同的遗传祖先而具有增加的遗传易感性，或者社会或环境因素是否解释了观察到的差异。使用来自动脉粥样硬化多种族研究（梅萨）的数据，Peralta博士将比较四个主要种族群体的肾功能下降率和CKD发病率，并测试可能的遗传和社会人口学机制来解释这些差异。提出了三个具体目标：目标1：比较四个主要种族/族裔组的肾功能下降率和慢性肾脏疾病发病率（高加索人、非洲裔美国人、西班牙裔美国人和华裔美国人）使用基于肌酐和胱抑素C的测量;目的2：评估遗传血统是否是种族群体中肾功能下降和慢性肾脏疾病事件的独立预测因子，并探讨目的3：评估个体和社区水平的社会经济特征与不同种族肾功能下降和肾脏疾病发病率的关系。 相关性：更好地了解肾功能障碍早期阶段肾功能下降的种族/民族差异所涉及的机制，可能会导致重要的干预措施和预防策略，以阻止这种昂贵的流行病。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Carmen A. Peralta, who proposes a novel, multi-disciplinary approach to understanding racial/ethnic 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 growing 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.