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

描述(由申请人提供)： 这是对卡门·A·佩拉尔塔博士的K23奖项的申请，他提出了一种新的、多学科的方法来理解肾功能下降的种族/民族差异。这项奖励将使佩拉尔塔博士拥有资源和受保护的时间，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、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差异的专家；以及(3)利用社会人口测量方法，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，佩拉尔塔博士组建了一个指导团队，成员包括她的赞助人和主要导师迈克尔·什利帕克博士(早期肾功能障碍的心血管并发症领域的专家)，以及两位共同导师：尼尔·里施博士(遗传流行病学家)和保拉·布雷夫曼博士(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，而进展到终末期肾脏疾病(ESRD)对少数族裔的影响也不同。非洲裔美国人和西班牙裔美国人是ESRD人口中增长最快的群体。尽管晚期肾脏疾病进展到终末期肾病的差异得到了很好的证明，但还没有研究评估美国不同种族/民族的慢性肾脏疾病(CKD)或早期肾功能下降的发病率。目前尚不清楚某些种族/民族群体是否由于共同的遗传祖先而具有更高的遗传倾向，或者社会或环境因素是否解释了观察到的差异。使用动脉粥样硬化多种族研究(MESA)的数据，佩拉尔塔博士将比较四个主要种族群体的肾功能减退和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。提出了三个具体目标：目标1：使用基于肌酐和胱抑素C的测量方法比较四个主要种族/民族(高加索人、非裔美国人、西班牙裔和华裔美国人)的肾功能下降和慢性肾脏疾病的发生率；目标2：评估遗传血统是否是种族内肾功能下降和慢性肾脏疾病发生的独立预测因素，并探讨基因-环境交互作用在肾功能下降和发生肾脏疾病中的作用；以及目标3：评估个人和邻里水平的社会经济特征与跨种族群体肾功能下降和发生肾脏疾病的关系。 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，可能导致重要的干预措施和预防战略，以遏制这一代价高昂的流行病。

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.