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.
(Relevance to Public Health) Proper identification of obesity and sarcopenia is imperative to determine associated risks to these metabolic conditions and to design and assess targeted treatment strategies. BMI, the current standard used to identify individuals at risk of metabolic disease, has significant limitations. The proposed study is the first step in a rigorous evaluation of sex- and race-specific fat mass index (kg/m2) and appendicular lean mass index (kg/m2) adjusted for fat mass index based on NHANES DXA data as superior indices of metabolic risk in chronic kidney disease patients. The findings will fill a vital knowledge gap regarding the contribution of lean mass and fat mass to metabolic disease in chronic kidney disease.
