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

项目总结/摘要 该提案建立在候选人对临床研究事业的承诺基础上， 对慢性肾脏病（CKD）成人的身体组成和临床结果感兴趣。核心 这一全面的职业发展计划的组成部分包括：1）先进的教学指导， 完成流行病学和临床研究硕士学位，2）实施假设- 一项研究项目，评估肥胖和相对肥胖的患病率和临床意义。 在国家健康和营养检查调查（NHANES）中患有和不患有CKD的成人中的肌肉减少症， 3)有针对性的指导和参与多学科的工作进展会议和研讨会，以及4） 通过与导师的持续合作，积累了主要数据收集和管理的经验 问题研究总体目标是为K23提案的制定提供信息，该提案最终将导致 改善CKD患者的营养、身体组成和结局。 肌肉减少症是终末期肾病（ESRD）的常见并发症， 发病率和死亡率。然而，在成人非肌肉萎缩症的患病率和临床意义， 尚未确定需要CKD的透析。肥胖在CKD人群中也很常见， 与进展为ESRD相关。较高的脂肪量与较高的肌肉量密切相关; 因此，肌肉减少症的常规定义可能无法捕获相对于脂肪质量的低肌肉质量 在具有较高脂肪量的人中，即相对少肌症。体重指数的测量并不能区分 肌肉和脂肪量之间的差异，因此可能会将肌肉减少症和/或过度的个体错误分类 肥胖症之前对CKD成人身体组成的研究基于高百分比的身体定义肥胖 脂肪（%BF）;然而，这是肌肉减少症患者肥胖的有限指数：在两个患有 相同的脂肪量，较低的瘦体重将导致较高的BF %。相比之下，脂肪质量指数（FMI kg/m2）是 与瘦体重无关的肥胖测量。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 3期患者）的成分数据 至5）以产生非典型瘦体重指数（ALMI， kg/m2）作为相对少肌症的量度。我们的初步数据表明， 与老年人的身体功能差和意外残疾有关，而传统的ALMI 措施不是。研究的目的是确定是否患病率和程度的相对 患有CKD的NHANES参与者的肌肉减少症和过度肥胖与没有CKD的参与者相比不同， 并确定相对肌肉减少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受试者。结果将确定CKD患者的最大风险，并告知 未来的干预措施，以改善身体组成。

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.