Sarcopenia, Relative Sarcopenia and Excess Adiposity in Chronic Kidney Disease

Abstract

Aims Conventional definitions of sarcopenia based on lean mass fail to capture low lean mass relative to fat mass, i.e., relative sarcopenia. Unlike percent body fat (%BF) and Quételet's (body mass) index (BMI, kg/m 2 ), definitions of obesity based on fat mass index (FMI, kg/m 2 ) are not confounded by lean mass. The objective is to determine the prevalence of sarcopenia, relative sarcopenia, and obesity in CKD, and determine if CKD is associated with relative sarcopenia and obesity, independent of demographics and comorbidities.Methods and Results DXA-derived appendicular lean mass index (ALMI, kg/m 2 ) and FMI were assessed in 13,980 NHANES participants. ALMI, FMI, and ALMI relative to FMI (ALMI FMI ) were expressed as sex-and race/ethnicity-specific standard deviation scores compared with young adults (T-scores) and by age (Z-scores). Sarcopenia was defined as ALMI T-score < -2, relative sarcopenia as ALMI FMI T-score < -2, and low lean mass relative to fat mass for age as ALMI FMI Z-score < -1. Obesity was defined using conventional BMI and %BF cutpoints and as sex-and race/ethnicity-specific FMI cutpoints. Glomerular filtration rate (GFR) was estimated using creatinine-(eGFR Cr ) and cystatin C-(eGFR Cys ). The prevalence of relative sarcopenia was higher than the prevalence of sarcopenia, especially in CKD stages 3b and 4 using eGFR Cr ; these CKD stages were associated with the highest FMI. CKD stage was independently associated with low ALMI FMI for age using eGFR Cys . BMI underestimated and %BF overestimated the prevalence of obesity compared with FMI. CKD was not independently associated with obesity by FMI. ConclusionsIn CKD, conventional definitions of sarcopenia underestimate muscle deficits and %BF overestimates the prevalence of obesity. CKD is independently associated with relative sarcopenia, but not excess adiposity.

Relative sarcopenia and mortality and the modifying effects of chronic kidney disease and adiposity

“…Because of the known sex and race/ethnicity differences in muscle mass, our definitions are sex and race/ethnicity specific. Compared with sarcopenia, we found a higher prevalence of relative sarcopenia in an NHANES cohort . Further, compared with sarcopenia, relative sarcopenia demonstrated stronger correlations with physical function in patients with rheumatoid arthritis and better discriminated those with poor physical functioning and a higher risk of incident disability in the general elderly population .…”

“…Given the nearly 40% prevalence of obesity in the general population of the United States, traditional estimates of muscle mass that do not account for body size fail to appreciate relatively low muscle mass in a substantial proportion of the population. This issue is particularly problematic in disease states such as CKD with a higher prevalence of obesity compared with the general population . Our study is the first to examine and detect a significant association of relative sarcopenia with mortality.…”

“…This misclassification would result in an overestimate of the association between sarcopenia and relative sarcopenia with mortality among those with CKD. Finally, we previously reported that stage 5 CKD was associated with lower FMI compared with those with less advanced CKD . The NHANES cohort used for this study contains few individuals with eGFR <15 mL/min/1.73 m 2 thereby limiting the generalizability to those with advanced CKD …”

“…We hypothesized that both sarcopenia and relative sarcopenia are associated with mortality regardless of CKD status. Given the known higher prevalence of relative sarcopenia compared with sarcopenia in NHANES participants, we hypothesized that relative sarcopenia contributes to a higher proportion of deaths at the population level [population attributable risk (PAR)]. A number of prior studies have observed a survival advantage of overweight and mildly or moderately obese persons compared with those with normal weight among the elderly and chronic disease states (often termed the ‘obesity paradox’) .…”

“…A reduction in skeletal muscle mass and strength, sarcopenia, can gradually occur with age 1,2 and is associated with mortality across many populations 3,4 including patients with end stage renal disease, 5,6 among whom more than 20% have sarcopenia. 7,8 Patients with chronic kidney disease (CKD) not requiring dialysis also have a high prevalence of sarcopenia [9][10][11] although previous studies evaluating associations between sarcopenia and mortality in CKD have shown inconsistent results. [12][13][14] Muscle mass is directly correlated with fat mass such that with higher fat mass, there is generally a compensatory increase in muscle mass.…”