Should We Consider Sarcopenia in Pediatric Patients with Chronic Kidney Disease? A Preliminary Cross-sectional Analysis

doi:10.21203/rs.3.rs-2953906/v1

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Research Article

Should We Consider Sarcopenia in Pediatric Patients with Chronic Kidney Disease? A Preliminary Cross-sectional Analysis

https://doi.org/10.21203/rs.3.rs-2953906/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 11 Aug, 2023

Read the published version in Pediatric Nephrology →

You are reading this latest preprint version

Objective

We investigated sarcopenia and its traits in children and adolescents with chronic kidney disease.

Methods

Physical function was assessed using handgrip strength (HGS) and the 60-second sit-to-stand (STS-60). Body composition was assessed by bioelectrical impedance and anthropometry through mid-upper arm circumference (MUAC). Probable sarcopenia was considered as low HGS, whereas sarcopenia by adding low MUAC.

Results

Twenty-two patients were evaluated (11 ± 4 years and 59% boys). Sarcopenia prevalence was 50%. Low physical function by HGS and STS-60 was 59% and 100%, respectively, while low MUAC in 77%. HGS was positively associated with all body composition variables in the non-dialysis and peritoneal dialysis groups; on the other hand, the STS-60 was not significantly associated with any of the body composition variables.

Conclusion

Among pediatric patients with CKD, the prevalence of sarcopenia was high. Therefore, strategic interventions to body composition will likely confer positive benefits on HGS, but not on STS-60.

nutrition

muscle mass

muscle strength

dialysis

children

A successful treatment for pediatric patients with CKD depends on the complexity of factors¹. Nutritional status and body composition are important². In children and adolescents with CKD, cachexia and protein-energy wasting are common conditions³. Additionally, physical function play an important role⁴.

Low muscle strength is evidenced in the wide spectrum of pediatric patients⁵. This well-known sarcopenia trait has been associated with mortality in adults with CKD⁶. The ‘pediatric inactivity triad’ (i.e., exercise deficit disorder, pediatric dynapenia, and physical illiteracy) has been recently introduced to pediatric patients⁷. This triad may result in a cycle of decreased physical functioning and reduced physical activity, which occurs early in the disease process and progressively aggravates.

However, there are still gaps to comprehensively elucidate if sarcopenia should be considered for pediatric patients with CKD. Therefore, our study aimed to investigate sarcopenia in pediatric patients with CKD.

Study Design and Participants

This cross-sectional study was conducted at the pediatric nephrology division of Hospital da Criança de Brasília José de Alencar, Brazil, between March and May 2021. The study sample consisted of children and adolescents on dialysis and under non-dialysis treatment (CKD stages 3, 4, and 5). Pediatric patients (≥ 4 and < 18 years old) with a CKD diagnosis ≥ 3 months, and routinely attending the nephrology division were eligible. Those whose parents did not give consent, who had been hospitalized within the last three months, or with missing data on body composition and physical function were not included.

Clinical and demographic characteristics were obtained from medical records. Written informed consent was obtained from all participants and their parents. This research project was reviewed and approved by the Institutional Review Board (#4.579.842) and adhered to the Declaration of Helsinki.

Measurement of Body Composition and Anthropometry

Body composition was evaluated using an octopolar bioelectrical impedance analysis device (InBody S10). Surface electrodes were placed on both sides of the body on the dorsal surface of the hands and feet. The device assessed skeletal muscle mass (kg), fat mass (kg), and body fat (%). We measured anthropometric circumferences from the mid-upper arm circumference (MUAC) and waist circumference regions using inextensible tape. Triceps skinfold was measured with a standard skinfold caliper (Lange®). Body mass index (BMI) for age in z-score was classified as underweight, normal weight, and overweight⁸.

Assessment of Physical Function

Handgrip strength was evaluated using a hydraulic dynamometer (Saehan Corporation). The dominant arm for those with catheter access or arm without the arteriovenous fistula was assessed in the hemodialysis group. Patients were assessed in a seated position and elbows flexed at 90º. A total of three measurements were performed with a 1-min rest interval between attempts. The highest value was recorded for further analysis.

For the 60-second sit-to-stand test (STS-60), patients were asked to rise from a seated position without using their arms as quickly as possible for 60 seconds. If the patient did not have enough height to maintain feet on the floor, we used a step. The repetitions to complete the 60-second test was recorded.

Diagnoses of Sarcopenia

Age and gender normative reference values from healthy pediatrics were used for identifying body composition phenotypes, poor physical function, and sarcopenia. Low MUAC was defined as below the < 50th percentile values of a North American population⁹, as there is no Brazilian data available. Low handgrip strength was based on Brazilian data¹⁰ by using mean and standard deviation values, here named as ‘probable sarcopenia’ as recommended by the revised European Working Group in Sarcopenia in Older People consensus¹¹. As there is no Brazilian data available, low STS-60 was based on European data¹² by using the percentile 25. Sarcopenia was diagnosed as the presence of low handgrip strength in addition to low MUAC.

Statistical Analyses

Normality of data was checked with the Shapiro-Wilk test and histogram visual inspections. The continuous variables of the different pediatric CKD groups were compared by one-way analysis of variance or Kruskal-Wallis tests. To compare categorical variables, Fisher’s exact test was adopted. Pearson’s or Kendall's correlation tests analyzed the association between physical function and body composition. The strength of the correlation was classified as weak (r = < 0.30), moderate (r = 0.30 to 0.60), strong (r = 0.60 to 0.90), very strong (r = 0.90 to 0.99), and perfect (r = 1.0). We used the SPSS (version 26.0, IBM Corp.) and GraphPad Prism (version 8.0, GraphPad Software). A p-value ≤ .05 was considered to indicate statistical significance.

Characterization

Forty-nine pediatric patients from the division of nephrology were invited to participate and assessed according to eligibility criteria. Thirteen were not eligible and 14 did not consent. The final analyzed sample consisted of 22 patients, eight non-dialysis (36%), six on hemodialysis (27%), and eight on peritoneal dialysis (36%). The overall mean age was 11 ± 4 years, most of the patients were boys (59%). For the comparisons in physical function and body composition, no differences were seen among the CKD groups.

Prevalence of Sarcopenia and its Traits

Low handgrip strength (i.e., probable sarcopenia) was found in 59% (n = 13), while sarcopenia in 50% (n = 11). The hemodialysis group showed frequencies ≥ 50% for all the phenotypes, but no significant differences were found among the groups (Fig. 1).

Association between Physical Function and Body Composition

Handgrip strength showed to be positively associated with all body composition variables in the non-dialysis and peritoneal dialysis groups. The hemodialysis group showed significant associations for handgrip strength only with muscle mass (r = .91; p = .011), which was also strong and very strongly associated with the other groups (r = .87; p = .005 and r = .96; p = < .001, respectively). STS-60 performance did not show any significant association with body composition in all groups.

In the present study, we found that sarcopenia and traits (e.g., poor physical function and low MUAC) were prevalent in all groups of pediatric patients with CKD. Moreover, we also found strong to very strong positive associations between handgrip strength and body composition (i.e., muscle mass, fat mass, MUAC, and waist circumference) only in those non-dialysis and peritoneal dialysis groups. On the other hand, STS-60 was not significantly associated with any of the body composition variables. These data demonstrate that pediatric patients with CKD have poor musculoskeletal health and need preventive interventions to countermeasure such phenotypes.

Physical function and body composition assessments are challenging in CKD patients. Children and adolescents undergoing dialysis and following a kidney transplant have muscle strength below the normative values and those on dialysis had a lower exercise capacity and were physically inactive¹³. Handgrip strength seems to be more impaired in the advanced stages (i.e., kidney failure)¹⁴. Thus, this well-established sarcopenia trait (i.e., low muscle strength) is a common feature in pediatric patients with CKD.

Loss of muscle mass, myopathy, and central activation failure are involved in the process leading to muscle weakness⁵. Our evidence showed that sarcopenia, despite being an age-related condition, is prevalent and may be seen at early ages (i.e., pediatric) due to the catabolic environment promoted by the CKD itself. This emphasizes the importance of screening and monitoring for sarcopenia traits even at early ages. Our findings Also demonstrated handgrip strength to be more strongly associated with body composition than STS-60. This may be explained because an STS-based test does not require a maximal voluntary muscular contraction, demanding other physical components such as balance, which barely imposes physical exertion. Although not the STS-60, in CKD adults, STS-5 showed a weak association with lower limb strength by leg extension¹⁵. Therefore, STS-based tests may not be as reliable as handgrip strength for assessing maximal muscle strength also in pediatric patients with CKD.

There is not yet a well-established pharmacological treatment for CKD-related conditions in pediatric patients concerning physical function and body composition, but the existence of an ‘inactivity triad’ (i.e., exercise deficit disorder, pediatric dynapenia, and physical illiteracy) in pediatric patients with CKD⁷ reinforces the need for well-tailored interventions with the combination of exercise/physical activity and nutrition, which might be a key element for the prevention of muscle loss and poor physical function.

The present study has strengths. We included patients from different stages and kidney replacement therapies, picturing part of the CKD spectrum. Also, we measured physical function from different body limbs, while previous studies have not. Nevertheless, we recognize some limitations. Despite the sample being represented by part of the CKD spectrum, we had a small sample size available. The absence of a control healthy group (i.e., without CKD) does not allow a clear comprehension of how CKD affects physical function and body composition in pediatrics. Lastly, the high frequency (all patients) of low STS performance may have been biased due to the reference values and criteria applied and should be carefully interpreted.

We may conclude that poor physical function and sarcopenia were prevalent conditions in pediatric patients with CKD. Moreover, physical function by handgrip strength was strongly associated with body composition, but not in the hemodialysis group. These findings indicate that physical function may interact with body composition and should be routinely assessed in pediatric nephrology divisions. Thus, early therapeutic interventions aiming at benefits in musculoskeletal health (i.e., exercise/physical activity and nutrition) should be considered in pediatric patients with CKD, as they may modify poor physical function and promote healthier growing until adulthood.

Disclosure

The authors have no relevant financial or non-financial interests to disclose.

Acknowledgments

We thank all parents who allowed their children to participate in this study. Also, special thanks to the nephrology staff for supporting the data collection and to the Hospital da Criança de Brasília José Alencar for providing all the infrastructure and facilities.

Authors’ contributions

HSR: conceptualization, methodology, supervision, project administration, writing – original draft.

ACB, RSB, GID, and CCG: conceptualization, methodology, investigation, data collection, visualization, writing – review & editing.

TJW, and MPD: methodology, writing – review & editing.

NDG: resources, supervision, methodology, writing – review & editing.

Data availability statement

Data is available upon request.

Funding statement

No funding was received for conducting this study.

Conflict of interest disclosure

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval statement

This research project was reviewed and approved by the Institutional Review Board of Hospital da Criança de Brasília José Alencar (#4.579.842).

Patient consent statement

Written informed consent was obtained from all participants and their parents.

Kaspar CDW, Bholah R, Bunchman TE (2016) A Review of Pediatric Chronic Kidney Disease. Blood Purif 41:211–217
Mastrangelo A, Paglialonga F, Edefonti A (2014) Assessment of nutritional status in children with chronic kidney disease and on dialysis. Pediatr Nephrol 29:1349–1358
Mak RH (2016) Cachexia in children with chronic kidney disease: challenges in diagnosis and treatment. Curr Opin Support Palliat Care 10:293–297
Hogan J, Schneider MF, Pai R et al (2020) Grip strength in children with chronic kidney disease. Pediatr Nephrol 35:891–899
Alaylı G, Özkaya O, Bek K et al (2008) Physical function, muscle strength and muscle mass in children on peritoneal dialysis. Pediatr Nephrol 23:639–644
Ribeiro HS, Neri SGR, Oliveira JS et al (2022) Association between sarcopenia and clinical outcomes in chronic kidney disease patients: A systematic review and meta-analysis. Clin Nutr 41:1131–1140
Wilkinson TJ, O’Mahoney LL, Highton P et al (2022) Physical activity and the ‘pediatric inactivity triad’ in children living with chronic kidney disease: a narrative review. Ther Adv Chronic Dis 13:1–15
Ministério da Saúde. Orientações para a coleta e análise de dados antropométricos em serviços de saúde: Norma Técnica do Sistema de Vigilância Alimentar e Nutricional - SISVAN, Brasília (2011) https://bvsms.saude.gov.br/bvs/publicacoes/orientacoes_coleta_analise_dados_antropometricos.pdf
Addo OY, Himes JH, Zemel BS (2017) Reference ranges for midupper arm circumference, upper arm muscle area, and upper arm fat area in US children and adolescents aged 1–20 y. Am J Clin Nutr 105:111–120
Ferreira AC, de Shimano C, Mazzer AC (2011) Força de preensão palmar e pinças em indivíduos sadios entre 6 e 19 anos. Acta Ortopédica Bras 19:92–97
Cruz-Jentoft AJ, Bahat G, Bauer J et al (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48:16–31
Haile SR, Fühner T, Granacher U et al (2021) Reference values and validation of the 1-minute sit-to-stand test in healthy 5–16-year-old youth: a cross-sectional study. BMJ Open 11:e049143
Painter P, Krasnoff J, Mathias R (2007) Exercise capacity and physical fitness in pediatric dialysis and kidney transplant patients. Pediatr Nephrol 22:1030–1039
Bakr AElB, Hasaneen AM, AbdelRasoul BM, Helal Bassiouni D (2018) Assessment of Nutritional Status in Children With Chronic Kidney Disease Using Hand Grip Strength Tool. J Ren Nutr 28:265–269
Wilkinson TJ, Xenophontos S, Gould DW et al (2019) Test–retest reliability, validation, and “minimal detectable change” scores for frequently reported tests of objective physical function in patients with non-dialysis chronic kidney disease. Physiother Theory Pract 35:565–576

Download PDF

Journal Publication

published 11 Aug, 2023

Read the published version in Pediatric Nephrology →

Editorial decision: Major Revisions Needed
28 Jun, 2023
Reviewers agreed at journal
04 Jun, 2023
Reviewers invited by journal
22 May, 2023
Editor assigned by journal
19 May, 2023
First submitted to journal
18 May, 2023

You are reading this latest preprint version

Should We Consider Sarcopenia in Pediatric Patients with Chronic Kidney Disease? A Preliminary Cross-sectional Analysis

Status:

Journal Publication

Version 1

Abstract

Objective

Methods

Results

Conclusion

Figures

INTRODUCTION

MATERIALS AND METHODS

Study Design and Participants

Measurement of Body Composition and Anthropometry

Assessment of Physical Function

Diagnoses of Sarcopenia

Statistical Analyses

RESULTS

Characterization

Prevalence of Sarcopenia and its Traits

Association between Physical Function and Body Composition

DISCUSSION

CONCLUSION

Declarations

References

Status:

Journal Publication

Version 1