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

项目摘要/摘要 2016年，在美国发起透析的47,000人(约占所有透析事件的42% 那一年)患有肥胖症，体重指数(BMI)为每平方米30公斤≥。横穿 在BMI谱中，肾病患者通常在开始透析治疗后体重减轻。 然而，虽然患者的体重通常在透析的头几个月后稳定下来 如果没有肥胖，肥胖者通常会继续减肥。无论有没有肥胖的人都是 透析可能会由于肌肉萎缩和营养不良而减肥，最近的研究已经确定了体重 丢失是透析患者死亡的危险因素，与BMI无关。然而，一些体重减轻 在肥胖的透析患者中观察到的结果也可能反映了有意改善健康、活动能力或 获得肾移植的机会。目前，还没有指南来帮助临床医生区分 透析中肥胖患者的健康和高风险体重减轻。此外，典型的肥胖管理 考虑到以下因素，范例不容易移植到患有终末期肾病的肥胖者身上 这一人群中的慢性营养不良、炎症和石棺减少可能会改变 不同的减肥策略。因此，这项五年研究计划的首要目标是确定 在接受透析的肥胖者中，健康和高危体重减轻表型，并提供 在终末期肾脏疾病背景下改善肥胖管理的临床可行工具。我们会 通过进行三项不同但相互关联的研究来实现这一目标。在第一个研究中，我们将定性地 确定患者优先的减肥终点，以及患者、医生和其他利益相关者 透析中区分健康减肥和高危减肥的关键因素透视。在第二个 在这项研究中，我们将利用全国23,000名肥胖透析患者的数据集，并应用高和 低生理储备衍生出健康和高风险的减肥表型。然后我们会发展出一种重量- 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 将招募250名肥胖透析患者参加一项横跨美国五个地区的前瞻性纵向研究 各国评估营养、炎症和血流动力学生物标记物与 通常不会在登记数据中记录的健康轨迹的衡量标准，如骨肉减少、月经不调、 身体成分，以及患者优先的终点，如生活质量。在实现其目标的过程中，这 研究将提供迫切需要的知识和工具，以改善TENS的医疗管理 数以千计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中，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.