Frailty and Risk Prediction in Older Adults Considering Kidney Transplantation

描述(由申请人提供)：终末期肾病(ESRD)对老年人的影响不成比例：大约60%的透析患者年龄在e55岁。平均而言，接受肾移植(KT)的老年患者比透析患者的存活率更高。然而，老年患者转诊KT的比例比其他年龄组低得多，几乎是年轻患者转诊比例的1/7。关键的挑战在于确定KT的合适候选人。无法预测哪些老年患者将从KT中受益，哪些将受到损害，这是患者、移植医生和咨询肾脏科医生面临的最关键的难题之一。到目前为止，根据登记数据，使用为年轻患者设计的模型对年长的KT候选人进行了幼稚的评估。我们假设，专门针对老年患者的风险度量，但没有纳入国家登记或其他常规研究，将显著改善风险预测，从而提高临床决策， 转诊和临床护理。其中一个重要的衡量标准是虚弱，这是一种独立的综合征，表现为与住院人数增加、残疾和认知功能下降相关的生理储备减少，并预测内科和手术结果。此外，全身性炎症已被认为是将虚弱与多系统失调联系起来的一条途径。我们还假设，评估特定于老年患者的结果将增加风险预测模型的临床相关性。特别是，与年轻患者相比，老年人面临残疾、认知能力下降和生活质量下降的风险，特别是对透析、大手术和免疫抑制的反应。对于老年人来说，患者和同种异体移植物存活的传统模型可能不像考虑这些重要后果的模型那样相关。我们将前瞻性地量化600名老年透析患者和1000名接受KT的老年患者的脆弱性、IL-6、其他炎症标志物和预后之间的关系。然后，我们将把这些新的发现与我们以前根据登记册数据设计的风险预测模型结合起来，使用一种创新的方法，将我们的预期人口与登记册人口标准化。我们的预期数据与国家登记数据的创新整合将为我们提供统计能力，以确定微妙但重要的预测因素，并结合针对老年人的指标的新颖性。在此基础上，我们将为老年ESRD患者设计一个马尔可夫决策过程模型，比较透析和KT的结果。一个成功的决策过程模型将立即被患者、肾病学家和移植提供者使用。老年人的移植是一个不断发展的领域，但风险预测是利用与年龄无关的措施从基于人群的数据中得出的。结合新的衰老指标，如虚弱和IL-6，以及结果，如残疾，认知能力下降，和生活质量，将极大地改善考虑KT的老年人的临床决策。这项研究将解决日益增长的公共卫生挑战，即为美国30多万接受透析的老年人决定适当的治疗方案。

DESCRIPTION (provided by applicant): End stage renal disease (ESRD) disproportionately affects older adults: approximately 60% of dialysis patients are aged e55. On average, older patients who undergo kidney transplantation (KT) have a survival benefit over dialysis. However, referral for KT in older patients is much lower than for other age groups, at almost 1/7th the rate of referral for younger patients. The key challenge lies in identifying the appropriate candidates for KT. The inability to predict which older patients would benefit from KT, and which would be harmed, is one of the most critical dilemmas for patients, transplant physicians and referring nephrologists. To date, older KT candidates have been naively evaluated using models designed for younger patients based on registry data. We hypothesize that risk metrics specific to older patients, but not captured in national registries or other conventional studies, will significantly improve risk prediction and thus clinical decision-making, referral, and clinical care. One such important metric is frailty, an independent syndrome of decreased physiologic reserve associated with increased hospitalizations, disability and declining cognitive function, and predictive of medical and surgical outcomes. Additionally, systemic inflammation has been identified as a pathway linking frailty to multisystem dysregulation. We also hypothesize that evaluating outcomes specific to older patients will add clinical relevance to risk prediction models. In particular, compared with younger patients, older adults are at risk for disability, cognitive decline, and decreased quality of life, particularly i response to dialysis, major surgery, and immunosuppression. For older adults, conventional models of patient and allograft survival may not be nearly as relevant as ones which take into account these important consequences. We will prospectively quantify the association of frailty, IL-6, other inflammatory markers, and outcomes in 600 older incident dialysis patients and 1,000 older KT recipients. We will then integrate these novel findings with a risk prediction model we previously designed based on registry data, using an innovative approach of standardizing our prospective population to the registry population. The innovative integration of our prospective data with national registry data will provide us the statistical power to identify subtle but important predictors combined with the novelty of metrics specific to older adults. Based on this, we will design a Markov decision process model for older adults with ESRD, comparing outcomes between dialysis and KT. A successful decision process model will be immediately usable by patients, nephrologists, and transplant providers. Transplantation in older adults is a growing field, but risk prediction has been derived from population-based data utilizing age-independent measures. The incorporation of novel aging metrics, such as frailty and IL-6, and outcomes, such as disability, cognitive decline, and quality of life, will greatly improve clinical decision-making in older adults considering KT. This research will address the growing public health challenge of deciding appropriate treatment options for over 300,000 older adults on dialysis in the US.