Long-term outcomes among living kidney donors with isolated medical abnormalities

 描述(申请人提供)：肾移植供不应求。增加活体肾脏捐赠者的数量是一项主要优先事项。从历史上看， 活体捐献者在捐献时是健康的，没有孤立的医学异常(IMA)。最近，美国总体人口结构发生了变化，作为回应，移植中心现在包括患有IMA的捐赠者，如高血压前期(Pre-HTN)、肥胖和代谢综合征。在一般人群水平上，患有IMA的个人，特别是非裔美国人(AA)，更有可能发展为共病，如糖尿病、HTN和慢性肾脏疾病。最近的数据表明，AA活体肾脏捐赠者更有可能在捐献前有IMA。目前尚不清楚活体捐赠将对这些共病的发展产生什么影响，以及是否存在可归因于捐赠的风险的种族差异。目前评估活体捐赠者长期健康风险的方法并不准确，严重依赖于家庭和社会历史等传统因素。使用放射成像的形态测量方法(如血管钙化；脂肪分布)已成为心血管风险的有力预测指标。捐献前成像通常在捐献者评估期间获得，以评估肾脏解剖，可用于确定捐献后合并症的新的形态测量风险预测指标。我假设，形态测量方法将极大地改善对捐献后并发症的预测，包括直接归因于捐赠的风险。鉴于IMA患者在风险预测和分层方面的显著知识差距，我提议进行一项辅助研究，该研究将利用R01资助的活体捐赠者队列研究的数据，创建所研究的最大的IMA捐赠者队列，并将解决独特的目标：(1)探索新的形态测量方法和传统风险因素与按种族分层的捐赠后共病的关联；(2)开发预测捐赠后并发症的风险工具；以及(3)估计活体肾脏捐赠的风险。利用从常规捐献前成像获得的新的形态测量方法是创新的、高度实用的，并将创造出目前尚不存在的对活体捐赠者结局的风险预测水平。准确的风险预测将改善知情同意、捐赠者在医疗决策中的自主权，并将改变美国活体肾脏捐赠者选择的做法。阿拉巴马大学伯明翰分校的资源和基础设施，包括美国最多的AA活体肾脏捐赠者，与拟议的目标非常一致，并将提供必要的基础，以确保拟议的项目成功完成。导师奖将使我有机会专注于建立新的风险预测研究方面的专业知识，并增加我对少数群体中的健康差距和慢性病流行病学的接触，从而促进我作为一名独立调查员的成长。这一额外的培训将为我作为一名外科医生-科学家和R01基金的长期职业目标提供信息。

 DESCRIPTION (provided by applicant): The demand for kidney transplantation continues to exceed the supply. Increasing the number of living kidney donors is a major priority. Historically, living donors were healthy and free of isolated medical abnormalities (IMA) at the time of donation. Recently, general US population demographics have changed, and in response, transplant centers now include donors with IMAs such as pre-hypertension (pre-HTN), obesity, and metabolic syndrome. At a general population level, individuals with IMAs, particularly African Americans (AA), are more likely to develop comorbidities, such as diabetes, HTN, and chronic kidney disease. Recent data suggest that AA living kidney donors are more likely to have a pre-donation IMA. It remains unclear what impact, if any, living donation will have on development of these comorbidities, and whether racial disparities in risk attributable to donation exist. Current methods for assessing living donor long-term health risks are imprecise, relying heavily on traditional factors such as family and social histories. Morphometric measures (e.g. vascular calcifications; fat distribution), using radiologic imaging, have emerged as strong predictors of cardiovascular risk. Pre-donation imaging, routinely acquired during donor evaluations to assess renal anatomy, can be leveraged to identify novel morphometric risk predictors for post-donation comorbidities. I hypothesize that morphometric measures will greatly improve prediction of post-donation comorbidities, including risk directly attributable to donation. Given significant knowledge gaps in risk prediction and stratification of donors with IMAs, I propose an ancillary study that will leverage data from an ongoing R01-funded cohort study of live donors to create the largest cohort of IMA donors studied and will address unique aims: (1) explore the association of novel morphometric measures and traditional risk factors with post-donation comorbidity stratified by race; (2) develop a risk tool for predicting post-donation comorbidities; and (3) estimate risk attributable to living kidney donation. Utilization o novel morphometric measures obtained from routine pre- donation imaging is innovative, highly practical, and will create a level of risk prediction of living donor outcomes that currently does not exist. Precise risk prediction will improve informed consent, donor autonomy in medical decision making, and will change the practice of live kidney donor selection in the US. Resources and infrastructure at the University of Alabama at Birmingham, including the most AA living kidney donors in the US, are keenly in-line with the proposed aims, and will provide the necessary foundation to see the proposed project to its successful completion. The mentored award will foster my growth as an independent investigator by affording me opportunities to focus on building an expertise in novel risk prediction research and enhancing my exposure to health disparities and chronic disease epidemiology in minority populations. This additional training will inform my path toward long-term career goals of research independence as a surgeon-scientist and R01 funding.