ESRD-specific physiologic age: improving geriatric transplant prognostication

接受肾移植（KT）的终末期肾病（ESRD）老年人的寿命延长一倍 期待新的肾脏分配系统旨在更好地匹配受体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; 61-70岁的候选人下降10%，70岁以上的候选人下降24%。核心问题是， 器官共享网络（UNOS）决定，新分配系统的寿命匹配将是 基于估计移植后生存率（EPTS），这是一个仅包括实足年龄的简单模型， 糖尿病、透析时间和既往移植。EPTS在老年接受者中的预测能力较差; c- 老年人的EPTS统计量为0.59，低于年轻人的0.67。 我们假设，生理储备的措施将更准确地分层老年KT的风险 年龄比年龄大。我们的初步工作表明，弗里德脆弱表型， KT术后效果不佳虽然我们的发现令人鼓舞，但这种结构不太可能涵盖所有 与终末期肾病相关的生理储备的维度。很可能是油炸食品的某些特性 表型甚至与该人群无关。我们认为ESRD特异性的生理指标 除了虚弱和/或其他常规措施之外，储备将大大改善风险分层。 器官共享网络和器官移植界可能不愿意在有目的的节俭中增加一个新的变量， EPTS分数，这是争论了15年。我们的新方法得到了即将推出的UNOS的支持 主席，是在模型中以生理年龄取代生理年龄。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 生理年龄可改善老年ESRD患者的诊断。 为了实现这些目标，我们将利用现有数据，并在持续的纵向调查中收集新数据。 5,500名ESRD患者的队列研究。我们将从这些数据中提取有关生理储备成分的新数据， 母研究，并在辅助研究中额外招募2，342名新的ESRD患者， 生理储备成分是无法提取的。我们将测试以下目标：1）引出和 评估可能量化老年ESRD患者生理储备的新结构; 2）为了创建有效的， ESRD患者生理储备的可靠和普遍的测量; 3）测试是否替换 生理年龄与生理年龄相结合可改善老年受者的凝血功能。 这项工作将改善老年ESRD患者的诊断，这将有利于患者的选择， 知情同意书和病例组合调整的移植中心报告卡。我们的新方法， 生理年龄与生理年龄的时间年龄得到了UNOS领导层的支持， 对器官分配和优先顺序的影响，可能会改善老年KT候选人的获取。

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.