There are a number of limitations in the methodology used in this study. Pubertal status was not documented in this study. Using body composition measures relative to height-age carries the assumption that children of the same height-age will have the same pubertal status. Childhood CKD, especially those with advanced CKD, tends to have a higher incidence of delayed puberty. Foster et al. [10] studied body composition in children with CKD and expressed LBM and FM which were adjusted for sex, age, and pubertal status thus permitting a more accurate comparison of pediatric CKD patients with healthy controls.

Anorexia is an important component of previous criteria of PEW both in adults as well as children with CKD [3]. Yadav et al. did not assess this important patient-reported outcome, but instead measured total protein and energy intake by dietary recall. One important factor in determining the total caloric intake is the use of dietary supplements, which may be a major determinant of the incidence of PEW in children. Caloric supplements, actually taken not as prescribed, should be included in the calculation of total energy and protein intakes. The absence of such dietary management in anorexic patients could indeed result in high incidence of PEW in CKD patients. Data from the International Pediatric Peritoneal Dialysis Network [11] showed that the overall incidence of overweight is actually higher than that of underweight in children with CKD stage 5 on peritoneal dialysis, and that the geographically variable BMI status in pediatric CKD patients is highly dependent on the use of dietary supplements and in particular via tube or gastrostomy feeding. Yadav et al. disclosed that the compliance for nutritional supplement intake was poor in their patients partly due to cost (as the patients pay for all medications and supplements) and partly due to refusal by the child. These investigators did not ascertain actual total food intake including actual amounts of supplements consumed. None of the patients in this study were on tube or gastrostomy feeds. This could be an important contributory factor to the high incidence of PEW in this study compared to published results from the CKiD study [5].

Yadav et al. did not screen for factors contributing to PEW and muscle wasting. One important factor is the influence of physical activity (PA) and sedentary behavior (SB) on body composition in their study of children with CKD. Total PA and PA at moderate and high intensities may protect against the prevalence of muscle wasting and higher FM in older adults. SB, particularly screen time, may have detrimental effects on body composition. Daily duration of PA may have an important impact on body composition, more specifically proportion of LBM to FM [12]. Furthermore, recent evidence suggests that inflammation and hormone disturbance such as hyperparathyroidism and vitamin D deficiency [4] as well as growth hormone resistance [13] are important mediators of cachexia/PEW in CKD. rhGH has been FDA-approved for treatment of growth failure in children with CKD. In addition to its impact on linear growth, GH is important in maintaining normal LBM and FM [14]. Indeed there is experimental evidence that rhGH therapy is associated with reversal of cachexia/PEW and prevention of muscle wasting in CKD [15]. Randomized trials of rhGH in adult CKD patients showed benefits including weight gain, increased LBM, and improved muscle performance [16]. There was no information on GH therapy in Yadav’s study.

Other confounding factors to be considered in screening for PEW include sex, race, and CKD diagnosis. Foster et al. [10] showed that muscle deficits were greater in girls than boys, and greater in non-African American than African American children with CKD. Patients with glomerulonephritis had higher appendicular LBM than patients with congenital abnormalities of the kidney and urinary tract (CAKUT). Fluid overload in participants with glomerulonephritis and volume depletion in participants with CAKUT are possible explanations for this finding. Again, these factors were not considered in Yadav’s study.