Nutrition-Focused Physical Examination for Detecting Protein Energy Wasting in Children with Chronic Kidney Disease

Introduction

Undernutrition is known to occur in children with chronic kidney disease (CKD) and kidney failure (KF) and is governed by complex interactions between appetite, inflammation, dietary nutrient intake, comorbidities, increase energy expenditure, and metabolic rate. Protein energy wasting (PEW) is a distinct entity coined to describe the clinical consequences of anorexia, loss of muscle mass, and increased energy expenditure in the background of uremia.[1] In 2014, a revised criterion adapted from adult criterion was proposed for children that included five criteria – body mass index (BMI), mid-upper arm circumference (MUAC), biochemical measures [serum albumin, cholesterol, transferrin, C-reactive protein], reduced appetite, and short stature.[2] The chronic kidney disease in children (CKiD) study reported PEW to be present in 7–20%, which varied based on the number of criteria used.[2] Another study from a low middle income country revealed a higher burden of PEW in children with CKD 2–5 including those on dialysis and observed that anthropometry and appetite were more useful parameters compared to biochemical measures of assessment.[3] The diagnosis of PEW demands adequate facilities for blood tests and involves high costs. This could be a barrier for prompt diagnosis of PEW in under resourced regions. This calls for a need to explore point-of-care assessment tools to predict the risk of PEW that can be undertaken by health care professions, trained nurses, and dieticians.

Loss of muscle mass is a critical component of PEW. The CKiD study underscores the utility of MAC in assessing the severity of muscle loss and reports MAC to be associated with reduction in estimated glomerular filtration rate.[2] While MAC is a surrogate parameter for both muscle and fat loss, there is need to explore the role of a parameter that reflects muscle loss like mid-arm muscle area (MAMA) in these children. However, anthropometry parameters are known to have gaps in accuracy with questionable reliability in those with edema and bone deformities. A nutrition-focused physical examination (NFPE) serves as an important component of nutritional assessment, endorsed by the Accreditation Council for Education in Nutrition and Dietetics, that detects presence of fat loss (FL), muscle wasting (MW), and edema.[45] These simple bedside physical signs, though proposed for the assessment of nutrition in children, have not been studied in children with CKD.[6] This study was undertaken primarily to assess the profile of specific NFPE signs and MAMA in children with CKD (including dialysis). In addition, the role of NFPE as a point-of-care assessment in the diagnosis of PEW was studied.

Methods

This cross-sectional study was undertaken in children aged 2–18 years with CKD stages 2–4 and those on dialysis (for at least 1 month). The analysis reported here is a subset of an ongoing larger single-center study on PEW in children with CKD undertaken from April 2017 to June 2021. Recruitment of children was done at the pediatric CKD clinic of a tertiary care hospital. Those with bony deformities (in whom height could not be accurately recorded), sick children or those admitted in hospital within the last 1 month, and those who did not give consent for venipuncture for the study were excluded. Institutional ethical approval and informed consent from parents of children were obtained.

Diagnosis of PEW: Diagnosis of PEW was based on criteria used in the CKiD study.[2] Criteria included (a) biochemical parameters of serum cholesterol <100 mg/dL, serum albumin <3.8 g/dL, serum transferrin <140 mg/dL, and C reactive protein >3 mg/L; (b) BMI for height age <5^th centile, a marker of body mass; (c) MUAC <5^th centile, a marker of muscle mass; (d) decreased appetite; and (e) short stature defined by height for age <3^rd centile. Based on the number of criteria that each subject fulfilled, children were stratified as ^“Minimal PEW,” defined as fulfilling any parameters in two or more criteria of (a) through (e) or “Standard PEW” defined as any parameter fulfilled in three or more criteria or “Modified PEW” defined as fulfilling any parameter of the ≥3 or more criteria with short stature. For the purpose of this study, children were grouped into – a) those with PEW (who fulfilled any of the stratified categories) and b) those without PEW.

Body weight and height were recorded using a digital weighing scale (Tulaman Pvt. Ltd, India) to the nearest 0.05 kg and height recorded by a stadiometer (Standard steel, India) to the nearest 0.1 cm. Height for age percentile was calculated using reference charts of Indian Academy of Pediatrics.[7] BMI (weight in kg/height2) for height age (age at which the child’s current height is at 50^th centile) was calculated using CDC charts.[8] MUAC was measured using a nonmetal measuring tape to the nearest 0.1 cm and interpreted using reference charts based on centiles with a cut off of fifth centile being provided.[9] The assessment details of appetite and biochemical criteria are available in a previous study.[3]

Results

Eighty-six children with CKD stages 2–4 (50% males) and 40 on dialysis (60% males; 5 on hemodialysis and 35 on peritoneal dialysis) were studied. The median age (IQR) of those with CKD 2–4 and those on dialysis were 120.5 months (87,162) and 123.5 months (86,153.5), respectively. The median duration of CKD was 12 months (3,44) and duration on dialysis was 7.5 months (3,18). Most common etiology of CKD and kidney failure was congenital anomalies of kidney and the urinary tract (62%).

Discussion

This cross-sectional study reports a high burden of PEW in children with CKD, including those on dialysis. Importantly, this is one of the few studies in children with CKD that explores the role of NFPE – a noninvasive, cost-effective clinical tool to detect PEW. The findings of this study highlight the utility of NFPE parameters of MW and FL in the diagnosis of PEW in these children. MAMA found to have a low sensitivity to diagnose PEW in both groups. On the other hand, MW as a single parameter proved to have a high sensitivity and specificity to diagnose PEW in children with CKD and those on dialysis.

Muscle and fat loss leading to cachexia can result from undernutrition and chronic inflammatory states. The process involves gluconeogenesis, breakdown of adipocytes, release of acute phase reactants, and inflammatory cytokines that facilitate muscle degradation.[11] Further, there is evolving evidence to suggest that specific biomarkers like leptin, 25 hydroxyvitamin D levels, and interleukin -1 play a specific role in CKD-related cachexia.[121314] In pursuit of developing an inclusive criterion reflective of the complex interplay of nutrition and inflammation, the PEW criterion was proposed for adults. Thereafter, the criterion was adapted for use in children with CKD. In contrast to the CKiD study, we have reported the burden of PEW in children from a low middle income country to be as high as 59% in those with CKD2-4 and 58% in those with kidney failure.

Among the five criteria, anthropometry parameters of MAC, BMI, and height were useful to diagnose PEW in children with CKD and kidney failure. MAC and BMI, though cannot differentiate between fat and muscle mass, have been useful anthropometry parameters for PEW assessment in children with CKD.[3151617] Though MAC has been noted to be useful for assessment of undernutrition and frailty in these children,[318] it is a surrogate parameter that reflects subcutaneous fat tissue, bone, and muscle and may not be an ideal tool to specifically detect MW. The role of MAMA in determining MW or PEW has not been studied in children. In adults with CKD, MAMA was noted to be significantly associated with daily total protein intake.[19] One study from Egypt observed 66% of children on hemodialysis to have reduced muscle mass based on MAMA.[20] We observed low MAMA to be more commonly prevalent in the group with CKD (77%) than in those on dialysis (55%), while low MAC was noticed in lesser proportion of children in both groups (57 and 47.5%, respectively). This could possibly speculate the presence of reduced muscle mass and preserved/increased fat mass in these children. Besides, C-zeroT low MAMA found to have low sensitivity to diagnose PEW in both groups, making it a weak screening tool for PEW. This may be explained by the fact that MAMA reflects the upper-arm regional muscle area that may not be representative of MW present in other areas of the body.

The NFPE is a comprehensive approach that includes visual and tactile assessments for muscle and fat loss in children. Areas of the body that reflect MW and FL are specific and mutually exclusive. While muscles that best represent wasting are quadriceps, deltoids, temporalis, pectoralis, trapezius, supra and infraspinatus, and gastrocnemius, FL is well identified over the triceps, mid axillary line, iliac crest, buttocks, below ribs, and face.[10] In infants and toddlers, differentiating fat and muscle loss could be a challenge. The youngest child in this study being 7 years of age was not a limitation to undertaking NFPE. The pediatric specific NFPE provides guidance on the body areas that need to be examined for MW (temple, clavicle, shoulder, scapula, thigh, knee, and calf) and FL (face, arms, chest, and buttocks). Prominent bone structure at the clavicle, shoulder, scapula, knee sites, and flat or hollow areas in the upper or lower legs suggests that MW and hollow facial cheeks, depressions between ribs, and flat buttocks are key signs of FL. Our findings reveal severe MW and FL to be predominantly evident in children on dialysis. The parameters of FL, MW, and edema are components of NFPE that are incorporated into the SGNA. Signs of MW and FL were seen to highly correlate with the severity of SGNA rating of malnutrition in adults and children.[2021]

In the context of CKD, edema is a known confounding factor for nutritional assessment in CKD. Edema could be a result of protein losses through PD, proteinuria in those with underlying glomerular disease, and fluid retention. However, despite moderate edema being present in the majority, severe FL and MW were observed in about one-fifth to one-fourth of the cohort, respectively. Interestingly, low MAC was more commonly noted in children on dialysis compared to those with CKD 2–4 despite 47.5% of them presenting with edema. These findings suggest that certain physical findings may still be useful even in the presence of edema in a population with a high burden of undernutrition.

The clinical skill of NFPE is underutilized by clinicians, nurses, and dieticians in routine care of children with CKD. Some of the key reasons relate to lack of training and limited awareness of the tool and time constrains. Dieticians and nurses trained in adult related NFPE may find it unfamiliar to undertake such an assessment in children.[22] NFPE has received attention especially in the past few years and has been included in the training curriculum for registered dieticians. Hands on workshops and efforts to include NFPE into telehealth services are gaining momentum.[2324252627] A recent global survey on kidney nutrition care reveals low implementation of formal nutrition assessment for patients with CKD across the globe.[26] Empowering registered dieticians and nurses with methodical training for the point-of-care assessment of nutrition status is critical.[2829] NFPE is one such tools that have the potential for use at any level of health care delivery.

This is one of the very few studies that focused on the role of NFPE to identify undernutrition and PEW in children with CKD. The high burden of PEW in this population makes it feasible to study surrogate assessment tools. As a point-of-care assessment tool, NFPE could be easier compared to interpretation of BMI/MAMA using reference charts indexed to age/gender and height. Identifying specific signs for individual compartments of muscle and fat loss through NFPE provides added benefit as BMI cannot differentiate muscle from fat tissue. However, small sample size with small numbers in each of the categories of PEW limited further analysis of exploring the role of NFPE in detecting severity of PEW. Importantly, implementation of NFPE could be time consuming and demanding patient cooperation and trained assessors.

Conclusion

Clinical signs of MW and FL based on NFPE have a diagnostic ability to identify children with PEW. These findings reiterate the importance and relevance of NFPE in the assessment of children with CKD. Besides, NFPE has the potential to be instituted by trained nurses and dieticians as a point-of-care assessment for PEW in any health care context.