Burden of Chronic Kidney Disease in HIV Infection

描述（由申请人提供）： 该申请的总体目标是支持研究者的教育和临床研究，从而在以患者为导向的研究中获得独立的职业生涯，重点是HIV相关肾脏疾病。通过职业发展奖以及教学和科学培训方案，将通过以下方式实现这些目标：1）接受研究方法，统计分析，科学交流和手稿准备2）获得临床研究生培训计划的正式指导以及队列设计/统计分析和遗传流行病学的高级课程，以及3）在约翰霍普金斯医学院和公共卫生学院以及韦尔奇预防、流行病学和临床研究中心提供的支持性环境中，在导师和合作者的指导和投入下实施研究提案。艾滋病毒感染者的生存率在高效抗逆转录病毒疗法（HAART）的帮助下得到了显著改善;因此，慢性疾病如肾脏疾病越来越受到关注。该提案的总体目标是使用血清肌酐和胱抑素C量化艾滋病毒感染者慢性肾脏疾病（CKD）的负担，并调查艾滋病毒和宿主相关因素是否参与艾滋病毒阳性个体CKD的发展和进展。本提案将使用两个独特的研究人群：1）来自多中心艾滋病队列研究（MACS）和妇女机构间艾滋病研究（WIHS）队列的大量、种族多样的艾滋病病毒阳性个体，并进行了延长随访; 2）通过约翰霍普金斯艾滋病服务招募的艾滋病病毒阳性个体的基于临床的研究人群。该提案将提供：1）目前美国HIV相关CKD的流行病学及其对死亡率的影响; 2）比较基于胱抑素C与血清肌酐肾功能评估的CKD患病率; 3）调查与HAART和HIV疾病分期相关的CKD发生和进展风险;和4）MYH 9与CKD进展和特定肾组织病理学发现的关联的验证。 公共卫生相关性：该提案将对筛查和识别高危人群中的CKD产生重要影响。它将确定CKD在HIV感染自然史中的影响，并确定HAART时期CKD的风险因素。它将产生一个潜在的机制，艾滋病毒相关的慢性肾脏病，这可能最终导致艾滋病毒相关的慢性肾脏病的诊断和预后标志物的发展。

DESCRIPTION (provided by applicant): The overall goal of this application is to support the education and clinical research of the investigator leading to an independent career in patient-oriented research focused on HIV-related kidney disease. With the career development award and a program of didactic and scientific training, the goals will be achieved by: 1) receiving direct mentorship in study methods, statistical analysis, scientific communication and manuscript preparation 2) obtaining formal instruction in the Graduate Training Program in Clinical Investigation and advanced courses in cohort design/ statistical analysis and genetic epidemiology and 3) implementing the research proposal with guidance and input from mentors and collaborators in the supportive environment offered by the Johns Hopkins Schools of Medicine and Public Health, and the Welch Center for Prevention, Epidemiology and Clinical Research. Survival of HIV-infected individuals has improved significantly with highly active antiretroviral therapy (HAART); consequently, chronic illnesses such as kidney disease are of increasing concern. The overall aim of the proposal is to quantify the burden of chronic kidney disease (CKD) in HIV-infected individuals using serum creatinine and cystatin C and to investigate whether HIV- and host-related factors are involved in the development and progression of CKD in HIV-positive individuals. This proposal will use two unique study populations: 1) a large, racially diverse population of HIV-positive individuals with extended follow-up from the Multicenter AIDS Cohort Study (MACS) and the Womens' Interagency HIV Study (WIHS) cohorts; and 2) a clinic-based study population of HIV-positive individuals recruited through the Johns Hopkins HIV/AIDS Service. This proposal will provide: 1) the current epidemiology of HIV-related CKD in the U.S. and its impact on mortality; 2) a comparison of the prevalence of CKD based on cystatin C versus serum creatinine estimates of kidney function; 3) an investigation of the risk of CKD development and progression related to HAART and HIV disease stage; and 4) a validation of the association of MYH9 with CKD progression and specific renal histopathologic findings. PUBLIC HEALTH RELEVANCE: This proposal will have important implications in screening and identifying CKD in this high risk population. It will determine the impact of CKD in the natural history of HIV infection and determine risk factors for CKD during the HAART era. It will yield a potential mechanism for HIV-related CKD which may ultimately lead to the development of diagnostic and prognostic markers for HIV-related CKD.