Identifying Healthy and High-Risk Weight Loss Phenotypes to Optimize Obesity Management in End Stage Kidney Disease

项目总结/摘要 2016年，在美国有47，000人开始透析（约占所有透析事件的42%）， 该年的患者）患有肥胖症，体重指数（BMI）≥ 30 kg/m2。跨 在BMI谱中，患有肾脏疾病的个体在开始透析治疗后通常会减轻体重。 然而，尽管患者的体重通常在透析的最初几个月后稳定， 如果没有肥胖症，肥胖症患者的体重往往会继续下降。无论是有肥胖症还是没有肥胖症的人， 由于肌肉萎缩和营养不良，透析可能会减轻体重，最近的研究发现， 损失是透析患者死亡的危险因素，与BMI无关。然而，一些减肥 在肥胖透析患者中观察到的结果也可能反映了有意改善健康、活动性或 获得肾脏移植。目前，还没有指导方针来帮助临床医生区分 在接受透析的肥胖患者中，健康和高危体重减轻。此外，典型的肥胖管理 考虑到以下因素，这种模式不容易转移到患有终末期肾病的肥胖人群中， 慢性营养不良、炎症和肌肉减少症可能会改变 不同的减肥策略。因此，这项为期五年的研究提案的总体目标是确定 健康和高风险的体重减轻表型肥胖的人谁是透析，并提供 临床上可行的工具，以改善肥胖管理的设置终末期肾病。我们将 通过开展三项不同但相互关联的研究来实现这一目标。在第一项研究中，我们将定性地 除患者、医生和其他利益相关者外，确定患者优先的体重减轻终点 透析中区分健康和高风险体重减轻的关键因素。在第二 研究中，我们将利用23，000名肥胖透析患者的国家数据集，并应用高和 低生理储备，以获得健康和高风险的减肥表型。我们将开发一个权重- 损失风险计算器工具，可预测与每个体重相关的住院和死亡风险 损失表型，使用动态预测联合模型和机器学习技术。在第三项研究中，我们 将在美国五个地区招募250名肥胖透析患者进行前瞻性纵向研究。 评估营养、炎症和血流动力学生物标志物之间的相关性， 通常未在登记数据中捕获的健康轨迹的测量，例如肌肉减少症，运动障碍， 身体组成和患者优先的终点，如生活质量。为了实现其目标， 研究将提供迫切需要的知识和工具，将改善医疗管理的几十个 成千上万的终末期肾病和肥胖症患者，确保临床医生能够更好地 将患者优先的结果纳入减肥干预措施的评估，并认识到， 减轻高风险减肥的影响。

Project Summary/Abstract In 2016, 47,000 individuals who initiated dialysis in the United States (~42% of all incident dialysis patients that year) had obesity, with a body mass index (BMI) of ≥ 30 kilograms per meters squared. Across the BMI spectrum, individuals with kidney disease commonly lose weight after initiating dialysis treatment. However, whereas body weight typically stabilizes after the first several months of dialysis among patients without obesity, those with obesity often continue to lose weight. Both people with and without obesity who are on dialysis may lose weight due to muscle wasting and malnutrition, and recent studies have identified weight loss as a risk factor for death among people on dialysis, independent of BMI. Yet, some of the weight loss observed among obese dialysis patients may also reflect deliberate attempts to improve health, mobility, or access to kidney transplantation. Currently, there are no guidelines to help clinicians to differentiate between healthy and high-risk weight loss among people with obesity on dialysis. Further, typical obesity management paradigms are not easily transferrable to obese people with end-stage kidney disease, given factors such as chronic malnutrition, inflammation, and sarcopenia in this population that may modify the risks and benefits of different weight loss strategies. Therefore, the overarching goal of this five-year research proposal is to define healthy and high-risk weight loss phenotypes among people with obesity who are on dialysis, and to provide clinically feasible tools to improve obesity management in the setting of end-stage kidney disease. We will accomplish this goal by conducting three distinct but interrelated studies. In the first study, we will qualitatively determine patient-prioritized endpoints of weight loss, in addition to patient, physician and other stakeholder perspectives on the key factors that differentiate healthy from high-risk weight loss on dialysis. In the second study, we will leverage a national dataset of 23,000 obese dialysis patients and apply constructs of high and low physiologic reserve to derive healthy and high-risk weight loss phenotypes. We will then develop a weight- loss risk calculator tool that predicts the risks of hospitalization and death that are associated with each weight loss phenotype, using dynamic predictive joint models and machine learning techniques. In the third study, we will enroll 250 obese dialysis patients in a prospective, longitudinal study across five regions in the United States to evaluate the association between nutritional, inflammatory, and hemodynamic biomarkers and measures of health trajectory that are not typically captured in registry data, such as sarcopenia, dynapenia, body composition, and patient-prioritized endpoints such as quality of life. In accomplishing its aims, this research will provide urgently needed knowledge and tools that will improve the medical management of tens of thousands of people with end-stage kidney disease and obesity, ensuring that clinicians will be better able to incorporate patient-prioritized outcomes into assessments of weight loss interventions, and recognize and mitigate the effects of high-risk weight loss.