Trajectories of Kidney Dysfunction in Older Adults with Chronic Kidney Disease

描述(由申请人提供)： 在退伍军人人群中，慢性肾脏疾病(CKD)的患病率从18-44岁成年人的5%上升到85岁成年人的近50%。CKD定义为估计的肾小球滤过率(EGFR)和60ml/min/1.73m2。CKD与许多不良结局相关，包括终末期肾病(ESRD)的发展以及更高的死亡率、心血管疾病(CVD)、CKD相关并发症和功能下降。虽然患有CKD的老年退伍军人肾功能异常的存在明显与不良的健康结局有关，但这些患者中的许多人都有多种合并症，并在一系列器官系统中减少了功能储备。高血压、糖尿病和心血管疾病的患病率以及虚弱和残疾的负担在患有CKD的老年人中是相当严重的。在老年人群中，这些其他疾病的存在可能会削弱单纯以疾病为导向的方法的价值，该方法只关注内在肾脏异常在了解肾功能轨迹中的作用。相比之下，个性化的、以患者为中心的方法优先考虑患者的目标和偏好，并认识到老年人观察到的体征和症状通常是多因素的，反映了一个或多个慢性诱因和急性诱发事件之间的复杂相互作用。考虑到这一点，我们提出了一个增量研究议程，以更好地了解老年退伍军人不同纵向肾功能轨迹的预测因素、结果和意义。只有少数先前的研究评估了肾功能的纵向轨迹。这些研究表明，慢性肾脏病患者的肾功能轨迹有很大的异质性，许多患者遵循非线性疾病轨迹。此外，定性工作表明，CKD预期病程的不确定性似乎是患者和提供者的一个重要担忧。在目标1中，我们将使用多水平变化回归模型确定与患有CKD的老年退伍军人中EGFR轨迹下降相关的长期易感因素和短期诱发因素。除了传统的衡量肾脏疾病负担的指标外，我们还将评估一系列与老年人特别相关的时变因素，如药物的使用和剂量以及同时发生的健康事件，如急性疾病和住院。在目标2中，我们将评估不同的EGFR轨迹与传统CKD结局和与老年CKD相关的非传统、以患者为中心的结局(例如，疗养院入院)的相关性。最后，在目标3中，我们将检验老年退伍军人如何看待与CKD自我管理相关的挑战，并使用名义团体技术(NGT)沿不同的EGFR轨迹在特定点对其进行优先排序。了解这些障碍将使我们能够更好地让患者参与共同决策和解决问题的策略，并设计直接针对这些障碍的以患者和家庭为中心的干预措施。老年人特别容易受到健康状况变化或尖锐侮辱的影响。然而，先前的研究没有解决老年CKD患者健康的动态变化如何影响EGFR轨迹。此外，从患者的角度来看，我们不知道EGFR轨迹的意义。为了填补这些知识空白，我们提出了一种综合的方法，使用先进的统计方法和创新的定性成分，将确定(1)与EGFR轨迹下降相关的时变和基于事件的因素，(2)与EGFR轨迹相关的以患者为中心的结果，以及(3)患者报告的在EGFR轨迹中的特定点CKD自我管理的障碍。

DESCRIPTION (provided by applicant): In the VA population, the prevalence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, increases from <5% among adults 18-44 years old to nearly 50% among those >85 years old. CKD is associated with many adverse outcomes including the development of end-stage renal disease (ESRD) as well as higher rates of mortality, cardiovascular disease (CVD), CKD- related complications and functional decline. While the presence of abnormalities in kidney function in older Veterans with CKD are clearly associated with adverse health outcomes, many of these patients have multiple co-morbid conditions and diminished functional reserve across a range of organ systems. The prevalence of hypertension, diabetes, and CVD and the burden of frailty and disability are substantial in older adults with CKD. In the geriatric population, the presence of these other conditions may diminish the value of a purely disease-oriented approach that focuses only on the role of intrinsic kidney abnormalities in understanding trajectories of kidney function. In contrast, an individualized, patient-centered approach prioritizes patient goals and preferences and recognizes that observed signs and symptoms in older adults are often multi-factorial reflecting the complex interplay between one or more chronic predisposing and acute precipitating events. With this in mind, we propose an incremental research agenda to better understand the predictors, outcomes and significance of different longitudinal trajectories of kidney function in older Veterans. Only a few prior studies have evaluated longitudinal trajectories of kidney function. These studies demonstrate that there is substantial heterogeneity in kidney function trajectories in patients with CKD and that many patients follow a non-linear disease trajectory. Furthermore, qualitative work has suggested that uncertainty about the expected course of CKD appears to be an important concern among both patients and providers. In Aim 1, we will identify long- term predisposing factors and short-term precipitating factors associated with a decline in eGFR trajectory among older Veterans with CKD using multilevel change regression models. In addition to traditional measures of kidney disease burden, we will evaluate a range of time-varying factors of special relevance to older adults such as use and dosing of medications and intercurrent health events such as acute illness and hospitalization. In Aim 2, we will evaluate the association of different eGFR trajectories with both traditional CKD outcomes and nontraditional, patient-centered outcomes of relevance to older adults with CKD (e.g., nursing home admission). Finally, in Aim 3, we will examine how older Veterans view and prioritize challenges related to CKD self-management at specific points along different eGFR trajectories using the nominal group technique (NGT). Knowledge of these barriers will allow us to better engage patients in shared-decision making and problem solving strategies as well as design patient- and family-centered interventions directly targeting these barriers. Older adults are particularly vulnerable to changes in health status or acute insults. However, prior studies have not addressed how dynamic changes in the health of older CKD patients impact eGFR trajectory. Further we do not know the significance of eGFR trajectory from the patient's perspective. To fill these knowledge gaps we propose a comprehensive approach using both advanced statistical methods and an innovative qualitative component that will identify (1) time-varying and event-based factors associated with a decline in eGFR trajectory, (2) patient-centered outcomes associated with eGFR trajectory, and (3) patient-reported barriers to CKD self-management at specific points in eGFR trajectory.