Novel Control Group to Expand the Scope of the RELIVE Living Kidney Donor Study

描述(申请人提供)：尽管有近50年的临床经验，但活体肾脏捐赠的长期安全性尚不确定。在捐赠之前，活体肾脏捐赠者要经过仔细的体检。有肾脏或心血管疾病或危险因素(如糖尿病或高血压)以及其他严重疾病(如癌症)的候选捐赠者被排除在外。以前的一些研究试图通过比较活体肾脏捐赠者和未经筛查的普通人群队列的结果来评估活体捐献的风险。然而，这些未经筛选的队列不允许进行有意义的比较，因为它们不可避免地包括条件可能会阻止捐赠的个人。此外，以前对活体供者结局的大多数调查只检查了死亡率或终末期肾病(ESRD)的患病率。相反，我们提议的研究将使用两个现有的数据来源来比较描述良好的活体肾脏捐赠者队列的长期结果，这些人在捐赠年龄匹配，与相似的特征和筛选的对照组。我们将确定，在活体肾脏捐赠后，死亡、终末期肾病、慢性肾脏疾病、心血管疾病、高血压和/或贫血是否比这些匹配的非捐赠者更常见，否则他们本可以足够健康地进行捐赠。活体肾脏捐赠者数据来自肾和肺活体捐赠者评估(REIVE)数据库，该数据库包含1963至2007年间在美国三个移植中心之一捐献的8951名活体肾脏捐赠者的详细信息。通过与国家死亡指数(NDI)、医疗保险和医疗补助服务中心(CMS)、社会保障死亡总档案(SSDMF)和移植接受者科学登记/器官采购和移植网络(SRTR/OPTN)的数据链接，丰富了REIVE数据，以进一步确定死亡和ESRD。此外，一组存活的复发捐赠者(N=2,857)在2010至2012年间参与了后续调查和体检，以检测终末期肾病和肾脏相关疾病，如慢性肾脏疾病、心血管疾病、高血压和贫血。控制数据将从覆盖1971至2004年间大部分年份的6个横断面国民健康和营养检查调查(NHANES)队列中收集，并通过NDI和CMS联系对死亡率和健康状况进行最新的纵向跟踪。在NHANES参与时，有关于各种健康状况的数据，允许选择与活体肾脏捐赠筛查过程相似的控制措施的算法。重生捐赠和NHANES参与者的年份范围在很大程度上是重叠的，允许对年龄和出生队列匹配的配对进行类似的后续调查。由于这项研究将使用适当的对照组，包括最长的随访时间，并评估多种结果，因此它将提供迄今为止对活体肾脏捐赠的最佳长期评估。 公共卫生相关性：肾和肺活体捐赠者评估研究(REIVE)项目研究了1963至2007年间在美国三个移植中心捐献的活体肾脏捐赠者的医疗和生活质量结果。为了帮助医生、以前的捐赠者和正在考虑活体肾脏捐赠的人了解捐赠肾脏对预期寿命、未来的肾脏健康和整体健康的影响，我们计划将来自Relve研究的近9000名活体捐赠者与参与另一项关注美国整体健康的研究(NHANES)的人进行比较。来自NHANES的配对对照组将被选为在各个方面与复发的肾脏捐赠者相似且同样健康，除了没有捐赠肾脏之外。由于捐赠者和对照组之间的唯一区别将是肾脏捐赠，我们将能够对与捐赠本身相关的肾脏捐赠者的结果得出更准确的结论。

DESCRIPTION (provided by applicant): Despite nearly 50 years of clinical experience, the long-term safety of living kidney donation is not confidently known. Prior to donation, living kidney donors undergo careful medical screening. Candidate donors with kidney or cardiovascular disease or risk factors (such as diabetes or hypertension), and other serious medical conditions such as cancer are excluded. Some previous studies attempted to estimate the risk of living donation by comparing the outcomes of living kidney donors to unscreened general population cohorts. However, these unscreened cohorts do not allow for meaningful comparison, as they inevitably included individuals with conditions that would preclude donation. In addition, most previous investigations of living donor outcomes have examined only mortality or the prevalence of end-stage renal disease (ESRD). In contrast, our proposed study will use two existing data sources to compare long-term outcomes of a well-described cohort of living kidney donors matched at the age of donation to similarly-characterized and screened controls. We will determine whether death, ESRD, chronic kidney disease, cardiovascular disease, hypertension, and/or anemia become more common following living kidney donation than in these matched non-donors who would otherwise have been healthy enough to donate. Living kidney donor data are derived from the Renal and Lung Living Donors Evaluation (RELIVE) database, containing detailed information on 8,951 living kidney donors who donated at one of three US transplant centers between 1963 and 2007. The RELIVE data have been enriched with linkages to data from the National Death Index (NDI), Centers for Medicare & Medicaid Services (CMS), Social Security Death Master File (SSDMF), and Scientific Registry of Transplant Recipients/Organ Procurement and Transplantation Network (SRTR/OPTN) for additional ascertainment of death and ESRD. In addition, a subset of surviving RELIVE donors (N= 2,857) participated in follow-up surveys and physical assessments between 2010 and 2012 to detect ESRD and kidney-related morbidities such as chronic kidney disease, cardiovascular disease, hypertension, and anemia. Control data will be assembled from six cross-sectional National Health and Nutrition Examination Survey (NHANES) cohorts covering most years between 1971 and 2004, with newly available longitudinal follow-up of mortality and health status from NDI and CMS linkages. Data are available on myriad health conditions existing at the time of NHANES participation, allowing a selection algorithm for controls approximating the screening process for living kidney donation. The year ranges for RELIVE donations and NHANES participants are largely overlapping, allowing similar follow-up for age- and birth-cohort matched pairs. Because this study will use an appropriate control group, include the longest follow-up, and assess multiple outcomes, it will provide the best long-term assessment of live kidney donation to date. PUBLIC HEALTH RELEVANCE: The Renal and Lung Living Donors Evaluation Study (RELIVE) project studied medical and quality of life outcomes for living kidney donors who donated between 1963 and 2007 at three US transplant centers. In order to help doctors, previous donors, and people who are considering living kidney donation understand how donating a kidney affects life expectancy, future kidney health, and overall health, we plan to compare the nearly 9,000 living donors from the RELIVE study with people who participated in another study that looked at overall health in the United States (NHANES). The matched controls from NHANES will be chosen to be similar to and just as healthy as the RELIVE kidney donors in every way, except for not having donated a kidney. Since the only difference between the donors and the controls will be the kidney donation, we will be able to draw more accurate conclusions about kidney donor outcomes that are connected to the donation itself.