Frailty and Risk Prediction in Older Adults Considering Kidney Transplantation

考虑肾移植的老年人的虚弱和风险预测

• 批准号: 9266718
• 负责人: DORRY L. SEGEV
• 金额: $ 61.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9266718
• 关键词: Address; Affect; Age; Aging; Allografting; Biology; Cessation of life; Characteristics; Clinical; Cohort Studies; Comorbidity; Data; Data Collection; Dialysis patients; Dialysis procedure; Elderly; End stage renal failure; Enrollment; Functional disorder; Funding; Goals; Hospitalization; Immunosuppression; Impaired cognition; Inflammation; Inflammatory; Interleukin-6; Kidney Transplantation; Lead; Link; Measures; Medical; Modeling; Nature; Operative Surgical Procedures; Organ Donor; Outcome; Parents; Pathway interactions; Patients; Physicians; Physiological; Population; Process; Prospective cohort study; Provider; Public Health; Publishing; Quality of life; Registries; Renal dialysis; Reperfusion Injury; Research; Risk; Sample Size; Sampling; Standardization; Syndrome; Transplantation; United States; age group; aged; base; clinical care; clinical decision-making; clinically relevant; cognitive function; cytokine; data registry; delayed graft function; design; disability; follow-up; frailty; improved; inflammatory marker; innovation; model design; mortality; novel; older patient; outcome prediction; population based; predictive modeling; prospective; public health relevance; response; tool; transplant registry

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.

描述（由申请人提供）：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E55。平均而言，接受肾脏移植（KT）的老年患者比透析具有生存益处。但是，老年患者的KT转诊远低于其他年龄组，几乎是年轻患者转诊率的1/7。关键挑战在于确定KT的适当候选人。无法预测哪些老年患者将从KT中受益并受到损害，这是患者，移植医师和参考肾病学家最关键的困境之一。迄今为止，使用基于注册表数据为年轻患者设计的模型对年龄较大的KT候选者进行了天真的评估。 我们假设，特定于老年患者的风险指标，但在国家注册表或其他常规研究中未捕获的风险指标将显着改善风险预测，从而大大改善临床决策， 推荐和临床护理。一个这样的重要指标是脆弱的，这是一种独立的生理储备降低的综合征，与住院增加，残疾和认知功能的下降以及医学和外科手术结果的预测相关。另外，系统性炎症已被确定为将脆弱性与多系统失调联系起来的途径。我们还假设评估年长患者特有的结果将与风险预测模型相关。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危险，尤其是I对透析，重大手术和免疫抑制的反应。对于老年人，常规的患者和同种异体移植生存模型可能不如考虑到这些重要后果的模型。 我们将前瞻性地量化600名较老的透析患者和1,000名年龄较大的KT接受者的脆弱的IL-6，其他炎症标记和结果。然后，我们将使用以前基于注册表数据设计的风险预测模型将这些新颖的发现与风险预测模型相结合，并使用将我们的预期人群标准化为注册人群的创新方法。我们的前瞻性数据与国家注册表数据的创新整合将为我们提供统计能力，以识别微妙但重要的预测因子，并结合了特定于老年人的指标的新颖性。基于此，我们将为ESRD的老年人设计Markov决策过程模型，并比较透析和KT之间的结果。 成功的决策过程模型将立即由患者，肾脏病医生和移植提供者使用。老年人的移植是一个增长的领域，但是风险预测是​​从利用与年龄无关的措施的基于人群的数据得出的。新颖的衰老指标（例如脆弱和IL-6）的结合，以及诸如残疾，认知能力下降和生活质量之类的结果将大大改善考虑KT的老年人的临床决策。这项研究将面临日益增长的公共卫生挑战，即在美国为300,000多名老年人决定适当的治疗选择。