Frailty and Risk Prediction in Older Adults Considering Kidney Transplantation

描述（由申请人提供）：终末期肾病（ESRD）不成比例地影响老年人：约60%的透析患者年龄在55岁以上。平均而言，接受肾移植（KT）的老年患者的生存率高于透析。然而，老年患者转介KT的比例远低于其他年龄组，几乎是年轻患者转介率的1/7。关键的挑战在于为KT确定合适的候选人。无法预测哪些老年患者将受益于KT，哪些将受到伤害，这是患者，移植医生和转诊肾病学家最关键的困境之一。到目前为止，老年KT候选人已经天真地使用基于登记数据为年轻患者设计的模型进行了评估。 我们假设，特定于老年患者的风险指标，但未在国家登记或其他常规研究中获得，将显著改善风险预测，从而改善临床决策， 转诊和临床护理。其中一个重要指标是虚弱，这是一种独立的生理储备减少综合征，与住院率增加、残疾和认知功能下降相关，并可预测医疗和手术结果。此外，全身性炎症已被确定为连接虚弱与多系统失调的途径。我们还假设，评估老年患者的特定结局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，老年人有残疾、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，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。 我们将对600名老年透析患者和1,000名老年KT接受者的虚弱、IL-6、其他炎症标志物和结局的相关性进行前瞻性量化。然后，我们将这些新的发现与我们先前基于登记数据设计的风险预测模型相结合，使用一种将我们的前瞻性人群标准化为登记人群的创新方法。我们的前瞻性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，并结合老年人特有的指标的新颖性。在此基础上，我们将为ESRD老年人设计一个马尔可夫决策过程模型，比较透析和KT之间的结果。 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。老年人移植是一个不断发展的领域，但风险预测已来自基于人群的数据，利用年龄无关的措施。新的衰老指标（如虚弱和IL-6）和结果（如残疾，认知下降和生活质量）的结合将大大改善考虑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，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.