Prevalence and Clinical Significance of Relative Sarcopenia and Excess Adiposity in Adults with Chronic Kidney Disease

项目摘要/摘要 这项建议建立在候选人对临床研究和职业生涯所表现出的承诺之上 对成人慢性肾脏疾病(CKD)的身体成分和临床结果的兴趣。其核心是 这一全面的职业发展计划的组成部分包括：1)高级教学指导和 完成流行病学和临床研究的硕士学位，2)实现假设- 评估肥胖及其亲属增加的患病率和临床意义的驱动型研究项目 在国家健康和营养检查调查(NHANES)中，患有和不患有慢性肾脏病的成年人的骨量减少， 3)量身定做的指导和参加多学科进行中工作会议和研讨会，以及4) 通过与导师的持续协作进行主要数据收集和管理的经验 学习。首要目标是告知K23提案的发展情况，该提案最终将导致 改善慢性肾脏病患者的营养、身体成分和预后。 骨质疏松症是终末期肾病(ESRD)的一种常见并发症，与 发病率和死亡率。然而，成人非淋菌性骨质疏松症的患病率和临床意义 需要慢性肾脏病的透析尚未确定。肥胖在慢性肾脏病人群中也很常见，而且 与进展为终末期肾病相关。较高的脂肪质量与较高的肌肉质量密切相关； 因此，对骨质疏松症的传统定义可能不能涵盖相对于脂肪质量的低肌肉质量。 在脂肪质量较高的人群中，即相对石棺减少的人群中。对体重指数的测量不能区分 肌肉和脂肪质量之间的差异，因此可能会错误地对石棺减少和/或过度的个体进行分类 肥胖症。先前对CKD成人的身体成分的研究以高百分比的身体为基础定义肥胖 脂肪(%BF)；然而，对于患有石棺减少症的人来说，这是一个有限的肥胖指标：在两个患有 相同的脂肪质量，较低的瘦质量将导致较高的BF百分比。相反，脂肪质量指数(FMI千克/平方米)是 与瘦体重无关的肥胖度测量。拟议的研究将利用DXA机构 约14,000名NHANES参与者(包括1,075名CKD阶段3的参与者)提供了成分数据 至5)以产生针对年龄、性别和特定种族的阑尾瘦体重指数的标准偏差分数(Almi， Kg/m2)相对于FMI作为相对骨质疏松症的衡量标准。我们的初步数据表明，这一措施 与老年人的身体功能低下和意外残疾有关，而传统的 MEASURE并非如此。这项研究的目的是确定患者的患病率和相关程度 患有CKD的NHANES参与者与没有CKD的人相比，骨质疏松症和过度肥胖不同， 并确定相对骨质疏松症和过度肥胖是否与死亡风险增加有关 患有和不患有CKD的NHANES参与者。结果将确定CKD患者的风险最高，并向 未来的干预措施，以改善身体成分。

Project Summary/ Abstract This proposal builds upon the candidate's demonstrated commitment to a career in clinical research and interest in body composition and clinical outcomes in adults with chronic kidney disease (CKD). The core components of this comprehensive career development plan include: 1) advanced didactic instruction and completion of a Master's degree in Epidemiology and Clinical Research, 2) implementation of a hypothesis- driven research project evaluating the prevalence and clinical significance of increased adiposity and relative sarcopenia in adults with and without CKD in the National Health and Nutrition Examination Survey (NHANES), 3) tailored mentorship and participation in multidisciplinary work-in-progress conferences and seminars, and 4) experience with primary data collection and management through collaborations on the mentors' ongoing studies. The overarching goal is to inform the development of a K23 proposal that will ultimately lead to improved nutrition, body composition, and outcomes in patients with CKD. Sarcopenia is a frequent complication of end-stage renal disease (ESRD) and is associated with substantial morbidity and mortality. However, the prevalence and clinical significance of sarcopenia in adults with non- dialysis requiring CKD have not been established. Obesity is also common in the CKD population and is associated with progression to ESRD. Higher fat mass is strongly associated with higher muscle mass; therefore, conventional definitions of sarcopenia may fail to capture low muscle mass relative to fat mass among persons with higher fat mass, i.e. relative sarcopenia. Measures of body mass index do not distinguish between muscle and fat mass, and therefore may misclassify individuals with sarcopenia and/or excess adiposity. Prior studies of body composition in adults with CKD defined obesity based on a high percent body fat (%BF); however, this is a limited index of adiposity in those with sarcopenia: in two individuals with the same fat mass, a lower lean mass will result in a higher %BF. In contrast, fat mass index (FMI kg/m2) is a measure of adiposity that is independent of lean mass. The proposed study will leverage the DXA body composition data available in approximately 14,000 NHANES participants (including 1,075 with CKD stages 3 to 5) to generate age, sex and race-specific standard deviation scores for appendicular lean mass index (ALMI, kg/m2) relative to FMI as a measure of relative sarcopenia. Our preliminary data demonstrate that this measure was associated with poor physical function and incident disability in older adults while the conventional ALMI measure was not. The objectives of the study are to determine if the prevalence and degree of relative sarcopenia and excess adiposity differ in NHANES participants with CKD, compared to those without CKD, and to determine if relative sarcopenia and excess adiposity are associated with increased risk of mortality in NHANES participants with and without CKD. The results will identify CKD patients at greatest risk and inform future interventions to improve body composition.