ESRD-specific physiologic age: improving geriatric transplant prognostication

接受肾移植(KT)的终末期肾病(ESRD)老年患者寿命延长一倍 期望值。新的肾脏分配系统旨在更好地匹配受者和同种异体移植物的寿命， 已经生效两年了。在此期间，老年人获得KT的机会急剧下降；费率 61-70岁的应聘者下降10%，70岁的应聘者下降24%。核心问题是，美国 器官共享网络(UNOS)决定，新分配系统的长寿匹配将是 基于估计的移植后存活(EPTS)，一个简单的模型，只包括年龄段， 糖尿病、透析时间和移植前。EPTS在老年受助者中的预测能力较差； 老年受助者的EPTS统计量为0.59，低于年轻受助者的c统计量0.67。 我们假设，生理储备的测量将更准确地将老年KT中的风险分层 受助人的年龄要比实际年龄大。我们的初步工作表明，油炸脆性表型与 术后预后不佳。虽然我们的发现令人鼓舞，但这一结构不太可能涵盖所有 与终末期肾病相关的生理储备维度。很可能油炸脆性的一些属性 表型与这一群体甚至没有关系。我们相信ESRD特有的生理指标 储备，超越脆弱性和/或其他常规措施，将极大地改善风险分层。 UNOS和移植社区可能不愿为刻意节俭的 EPTS评分，争论了15年。我们的新方法，得到即将到来的联合国操作系统的支持 主席，是在模型中以生理年龄取代时序年龄。我们的首要目标是 研究将开发一种生理年龄计算器，并测试是否用 生理性年龄改善老年ESRD患者的预后。 为了实现这些目标，我们将利用现有数据并在持续的纵向范围内收集新数据 5500例终末期肾病患者的队列研究。我们将提取有关生理储备成分的新数据 家长研究并在辅助研究中招募另外2342名新的ESRD患者，该研究将直接测量 不能抽象的生理储备成分。我们将测试以下目标：1)引发和 评估可能量化老年ESRD患者生理储备的新结构；2)创建有效的、 对终末期肾病患者进行可靠的、可推广的生理储备测量；3)测试是否替代 具有生理年龄的年龄段改善了老年受者的预后。 这项工作将改善老年ESRD患者的预后，这将有利于患者的选择， 知情同意，以及病例组合调整后的移植中心成绩单。我们的新方法来取代 具有生理年龄的时间年龄得到了联合国操作系统领导层的支持，并可能立即 对器官分配和优先顺序的影响，可能会改善老年KT候选人的机会。

Older adults with end stage renal disease (ESRD) who receive kidney transplantation (KT) double their life expectancy. The new kidney allocation system, designed to better match longevity of recipients and allografts, has been in effect for 2 years. During this time, access to KT among older adults has plummeted; with rates declining 10% for candidates aged 61-70 and 24% for those aged >70. The core problem is that the United Network for Organ Sharing (UNOS) decided that longevity matching for the new allocation system would be based on Estimated Post-Transplant Survival (EPTS), a simple model that only includes chronologic age, diabetes, time on dialysis, and prior transplant. EPTS has poor predictive power among older recipients; the c- statistic of EPTS for older recipients is 0.59, which is lower than the c-statistic of 0.67 for younger recipients. We hypothesize that a measure of physiologic reserve will more accurately stratify risk among older KT recipients than chronologic age. Our preliminary work suggests that the Fried frailty phenotype, is associated with poor post-KT outcomes. While our findings are encouraging, it is unlikely that this construct captures all the dimensions of physiologic reserve associated with ESRD. It is likely that some attributes of the Fried frailty phenotype are not even relevant for this population. We believe an ESRD-specific measure of physiologic reserve, beyond frailty and/or other conventional measures, would greatly improve risk stratification. UNOS and the transplant community might be reluctant to add a new variable to the purposefully parsimonious EPTS score, which was debated for 15 years. Our novel approach, supported by the upcoming UNOS president, is to replace chronologic age with physiologic age in the model. The overarching goal of our research will be to develop a physiologic age calculator and test whether replacing chronologic age with physiologic age improves prognostication for older adults with ESRD. To achieve these goals, we will leverage existing data and collect new data within an ongoing longitudinal cohort study of 5,500 ESRD patients. We will abstract new data on components of physiologic reserve from the parent study and enroll an additional 2,342 new ESRD patients in an ancillary study which will directly measure the physiologic reserve components that cannot be abstracted. We will test the following aims: 1) To elicit and evaluate novel constructs that might quantify physiologic reserve in older ESRD patients; 2) To create a valid, reliable, and generalizable measure of physiologic reserve for ESRD patients; 3) To test if replacing chronologic age with physiologic age improves prognostication in older recipients. This work would improve prognostication for older adults with ESRD, which would benefit patient selection, informed consent, and case-mix adjusted transplant center report cards. Our novel approach to replacing chronologic age with physiologic age has the support of UNOS leadership and could have an immediate impact on organ allocation and prioritization, possibly improving access for older KT candidates.