Clinical Center: Medical and Quality of Life Outcomes after Live Kidney or Lung D

描述（由申请人提供）：在美国已经进行了70，000多例活体器官捐献，其中肾脏和肺部捐献分别占90%和0.8%。尽管已知供体肾切除术的术后供体并发症发生率为8-10%，供体肺叶切除术的术后供体并发症发生率为20-60%，但活体肾或肺捐献后的供体长期医疗和生活质量结局尚未得到充分研究。在肾脏捐献者中进行的观察性研究发现，高血压（30-35%）、慢性肾脏疾病[CKD]（1%）和2型糖尿病（5%）的患病率与美国总体人群相似。在一个小的，控制不好的系列中报告了捐献后心理障碍的风险增加了6倍。总体而言，现有研究受到以下限制：1）供体随访率不完整，为30-60%; 2）对照组缺失或方法学缺陷。 一个由10个临床中心组成的联盟在此提议进行三项流行病学研究。 研究1：将使用一个基于人群的历史前瞻性队列（包括10，000名肾脏供体和330名肺供体沿着）以及一个比较组（包括20，660名入组卫生专业人员随访研究和护士健康研究（HPFS/NHS）的受试者）来评价：（a）肾脏和肺供体的死亡风险和（B）肾脏供体的终末期肾病（ESRD）风险。 研究2：将在700例肾脏供体、330例肺移植患者的样本中进行横断面临床研究。 供体和1，030名配偶、兄弟姐妹和配偶对照，以：（a）评估肺供体肺功能障碍的风险;（B）确定活体器官捐献是否显著增加总共病负担、健康相关生活质量（HRQoL）受损、精神健康障碍或心理功能障碍的风险;和（c）确定肾脏供体中CKD、心血管疾病（CVD）、高血压和糖尿病的累积风险。 研究3：将在400例计划接受活体供肾切除术的受试者中进行一项为期12个月的前瞻性研究，以评估知情同意过程的多个方面。将分别使用Poisson回归和竞争风险模型分析死亡率和ESRD发生率。将使用多变量回归方法评估肺功能障碍、CVD、CKD、HRQoL降低、心理障碍和合并症指数升高的风险。拟议的研究具有85-93%的把握度，以确定与不良供体结局的禁止性风险相关的特征，并描述活体器官捐献的长期心理社会影响。

DESCRIPTION (provided by applicant): More than 70,000 live organ donations have been performed in the U.S. Of these, kidney and lung donations constitute 90% and 0.8%, respectively. Although, the rates of postoperative donor complications are known to be 8-10% for donor nephrectomy and 20-60% for donor lung lobectomy, the donor long-term medical and quality of life outcomes following live kidney or lung donation have not been well studied. Observational studies in kidney donors have found prevalent disease rates similar to the overall U.S. population for hypertension (30-35%), chronic kidney disease [CKD] (1%) and type 2 diabetes mellitus (5%). A six-fold increased risk of postdonation psychological impairment has been reported in small, poorly controlled series. In the aggregate, existing studies are limited by 1) incomplete donor follow-up rates of 30-60% and 2) absent or methodologically deficient comparator groups. A consortium of 10 clinical centers herein propose to perform three epidemiologic studies. Study 1: A population-based, historical, prospective cohort of 10,000 kidney donors and 330 lung donors along with a comparison group of 20,660 subjects enrolled in the Health Professionals Follow-up Study and the Nurses Health Study (HPFS/NHS) will be utilized to evaluate: (a) the risk of death in both kidney and lung donors and (b) the risk of end stage renal disease (ESRD) in kidney donors. Study 2: A cross-sectional clinical study will be performed in a sample of 700 kidney donors, 330 lung donors and 1,030 yoke, sibling and spousal controls to: (a) evaluate the risk of pulmonary dysfunction in lung donors; (b) determine whether live organ donation significantly increases the risk of total comorbid burden, impaired health-related quality of life (HRQoL), mental health disturbance or psychological dysfunction; and (c) determine the cumulative risk of CKD, cardiovascular disease (CVD), hypertension and diabetes mellitus in kidney donors. Study 3: A 12-month prospective study will be performed in 400 subjects scheduled for live donor nephrectomy, to assess multiple aspects of the informed consent process. Poisson regression and competing risk model will be used to analyze death rates and the incidence of ESRD, respectively. Multivariate regression methods will be used to assess the risks of pulmonary dysfunction, CVD, CKD, diminished HRQoL, psychological impairment and elevated comorbid indices. The proposed studies are powered at 85-93% to identify characteristics associated with prohibitive risks of adverse donor outcomes and to delineate the long-term psychosocial effects of live organ donation.