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

描述(申请人提供)：美国已经进行了超过7万例活体器官捐赠，其中肾脏和肺捐赠分别占90%和0.8%。虽然供体肾切除术后并发症的发生率为8-10%，供体肺叶切除术后供体并发症的发生率为20-60%，但活体肾或肺移植对供体的长期医疗和生活质量的影响尚未得到很好的研究。对肾脏捐赠者的观察性研究发现，高血压(30-35%)、慢性肾脏疾病(CKD)(1%)和2型糖尿病(5%)的患病率与美国总人口相似。据报道，捐献后心理损伤的风险增加了六倍，这是一系列控制不佳的小病例。总体而言，现有的研究受到以下因素的限制：1)供者随访率不完全，为30-60%；2)对照组不存在或在方法上存在缺陷。 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：由10,000名肾脏捐赠者和330名肺捐赠者组成的基于人群的历史前瞻性队列，以及参加卫生专业人员后续研究和护士健康研究(HPFS/NHS)的20,660名受试者组成的对照组，将被用来评估：(A)肾脏和肺捐赠者的死亡风险，以及(B)肾脏捐赠者的终末期肾脏疾病(ESRD)的风险。 研究2：一项横断面临床研究将在700名肾捐献者的330个肺样本中进行。 (A)评估肺捐赠者的肺功能障碍的风险；(B)确定活体器官捐赠是否显著增加总的并存负担、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；(C)确定肾脏捐赠者患慢性肾脏病、心血管疾病、高血压和糖尿病的累积风险。 研究3：一项为期12个月的前瞻性研究将在400名计划进行活体供肾切除的受试者中进行，以评估知情同意过程的多个方面。泊松回归和竞争风险模型将分别用于分析死亡率和终末期肾病的发病率。多元回归方法将用于评估肺功能障碍、CVD、CKD、HRQOL降低、心理损害和共病指数升高的风险。拟议的研究的动力在85-93%，以确定与不良捐赠者结局的令人望而却步的风险相关的特征，并描述活体器官捐赠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.