Should we consider sarcopenia in pediatric patients with chronic kidney disease? A preliminary cross-sectional analysis.

BACKGROUND: Pediatric patients with chronic kidney disease (CKD) frequently present an inadequate nutritional profile and musculoskeletal impairments. We investigated sarcopenia and its related traits in children and adolescents with CKD. METHODS: A cross-sectional study that enrolled pediatric patients with CKD (≥ 4 and < 18 years old). Physical function was assessed by handgrip strength and the 60-s sit-to-stand (STS-60) tests. Body composition measurement was performed by bioelectrical impedance analysis and anthropometry through mid-upper arm circumference (MUAC). Normative reference values from healthy pediatrics were used for identifying poor physical function and low MUAC. Probable sarcopenia was considered as low handgrip strength, whereas sarcopenia was defined by adding low MUAC. RESULTS: Twenty-two pediatric patients with CKD (11 ± 4 years and 59% boys) were evaluated; eight on peritoneal dialysis (36%), six on hemodialysis (27%), and eight non-dialysis (36%). Regarding sarcopenia traits, we observed low physical function by handgrip strength and STS-60 in 59% and 100% of the patients, respectively, while low MUAC in 77%. Probable sarcopenia was found in 9% and sarcopenia in 50%, but prevalence did not differ among stages. Handgrip strength was strongly associated with MUAC (r = 0.90; p < 0.001); 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 and its related traits was high. Nephrology professionals should consider the assessment of sarcopenia in this population, while more evidence is needed to determine its prognostic value. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Comparison of Dietary Patterns and Daily Food Intake Across Kidney Disease Stages in England: An A-Posteriori Cluster Analysis.

OBJECTIVE: Dietary patterns are rapidly becoming a major focus of medical nutrition therapy in chronic kidney disease (CKD) and the analysis of dietary patterns has emerged as a practical approach to evaluate qualitative as well as quantitative aspects of overall diet. In an a-posteriori data-driven approach, dietary patterns are based on the actual food intake of the population evaluated. Investigation of dietary patterns in CKD is not well-described, and to our knowledge, has not been conducted in a UK-based cohort. METHODS: Adult participants with a diagnosed kidney condition (CKD 1-5 not requiring dialysis) were recruited into a multicenter observational cross-sectional study. Dietary intake was assessed using the European Prospective Investigation of Cancer in Norfolk Food Frequency Questionnaire. Logistic Principal Component Analysis was used to identify food group clusters. Differences between groups were assessed using univariate general linear modeling. RESULTS: In total, 696 patients were included. The mean age was 64.7 (±14.0) years, 61% of the cohort were male. Most participants were White British (89%). The mean estimated glomerular filtration rate was 36.6 (±20.9) mL/minute/1.732. We found differences in food group intake across stages (e.g., greater intake of nuts and seeds intake in CKD 1-2 versus CKD 4) and across sex (e.g., females had a higher intake of fruit and vegetables versus males). Comparison with the reference cohort revealed that, overall, the CKD cohort had reduced intakes of food stuffs such as cereals and cereal products, but higher intakes of groups such as meat and meat products. There were limited differences in micronutrients, although vitamin B2 and calcium were higher in earlier stages. CONCLUSION: Overall, the findings from a novel a-posteriori approach underline the complex diversity of food patterns in CKD. The findings from our study may inform dieticians and other health-care providers about the need to consider treatment modalities and stages when giving dietary recommendations.

Skeletal Muscle Texture Assessment Using Ultrasonography: Comparison with Magnetic Resonance Imaging in Chronic Kidney Disease.

Skeletal muscle dysfunction is common in chronic kidney disease (CKD). Of interest is the concept of "muscle quality," of which measures include ultrasound-derived echo intensity (EI). Alternative parameters of muscle texture, for example, gray level of co-occurrence matrix (GCLM), are available and may circumvent limitations in EI. The validity of EI is limited in humans, particularly in chronic diseases. This study aimed to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Images of the thigh were acquired using a 3 Tesla MRI scanner. Quantification of muscle (contractile), fat (non-contractile), and miscellaneous (connective tissue, fascia) components were estimated. Anatomical rectus femoris cross-sectional area was measured using B-mode 2D ultrasonography. To assess muscle texture, first (i.e., EI)- and second (i.e., GLCM)-order statistical analyses were performed. Fourteen participants with CKD were included (age: 58.0 ± 11.9 years, 50% male, eGFR: 27.0 ± 7.4 ml/min/1.73m2, 55% Stage 4). Higher EI was associated with lower muscle % (quadriceps: ß = -.568, p = .034; hamstrings: ß = -.644, p = .010). Higher EI was associated with a higher fat % in the hamstrings (ß = -.626, p = .017). A higher angular second moment from GLCM analysis was associated with greater muscle % (ß = .570, p = .033) and lower fat % (ß = -.534, p = .049). A higher inverse difference moment was associated with greater muscle % (ß = .610, p = .021 and lower fat % (ß = -.599, p = .024). This is the first study to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Our preliminary findings suggest ultrasound-derived texture analysis provides a novel indicator of reduced skeletal muscle % and thus increased intramuscular fat.

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants.

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85-0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

A Systematic Review of Handgrip Strength Measurement in Clinical and Epidemiological Studies of Kidney Disease: Toward a Standardized Approach.

In chronic kidney disease (CKD), handgrip strength (HGS) is recommended as a surrogate measure of protein-energy status and functional status. However, it is not routinely used because of inconsistencies such as the optimal timing of the HGS measurement and unclear guidance regarding technique. We aimed to determine the extent of variation in the protocols and methods of HGS assessment. We aimed to identify clinical and epidemiological studies conducted on CKD that reported on the use of HGS as an outcome. A systematic literature search identified n = 129 studies with a total participant population of n = 35,192. We identified large variations in all aspects of the methodology including body and arm position, repetitions, rest time, timing, familiarization, and how scores were calculated. The heterogeneous methodologies used reinforce the need to standardize HGS measurement. After reviewing previously employed methodology in the literature, we propose a comprehensive HGS assessment protocol for use in CKD.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

BACKGROUND: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. OBJECTIVE: This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). METHODS: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. RESULTS: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. CONCLUSIONS: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clearly defined but may involve reductions in mitochondrial function, mass and biogenesis. Here we report on the effect of non-dialysis dependent CKD (NDD-CKD) on mitochondrial mass and basal expression of transcription factors involved in mitochondrial biogenesis compared to a healthy control cohort (HC). In addition, we sought to investigate the effect of a 12-week exercise-training programme on these aspects of mitochondrial dysfunction in a NDD-CKD cohort.For the comparison between NDD-CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis (VL) of n=16 non-dialysis dependent CKD patient's stage 3b-5 (NDD-CKD) and n=16 healthy controls matched for age, gender and physical activity (HC). To investigate the effect of exercise training, VL biopsies were collected from n=17 NDD-CKD patients before and after a 12-week exercise intervention that was comprised of aerobic exercise (AE) or a combination of aerobic exercise and resistance training (CE). Mitochondrial mass was analysed by citrate synthase activity and mitochondrial protein content by Porin expression, whilst the expression of transcription factors involved in mitochondrial biogenesis were quantified by real-time qPCR. NDD-CKD patients exhibited a significant reduction in mitochondrial mass when compared to HC, coupled to a reduction in PGC-1α, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression. 12-weeks of exercise training resulted in a significant increase in PGC-1α expression in both groups, with no further changes seen across indicators of mitochondrial biogenesis. No significant changes in mitochondrial mass were observed in response to either exercise programme. NDD-CKD patients exhibit reduced skeletal muscle mitochondrial mass and gene expression of transcription factors involved in mitochondrial biogenesis compared to HC. These reductions were not restored following 12-weeks of exercise training implying exercise resistance in this cohort. The reasons for this lack of improvement are currently unknown and require further investigation, as reversing the dysregulation of these processes in NDD-CKD may provide a therapeutic opportunity to improve muscle fatigue and dysfunction in this population.

Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study.

BACKGROUND: People with chronic kidney disease (CKD) report high levels of physical inactivity, a major modifiable risk factor for morbidity and mortality. Understanding the biological, psychosocial and demographic causes of physical activity behaviour is essential for the development and improvement of potential health interventions and promotional initiatives. This study investigated the prevalence of physical inactivity and determined individual correlates of this behaviour in a large sample of patients across the spectrum of kidney disease. METHODS: A total of 5656 people across all stages of CKD (1-2, 3, 4-5, haemodialysis, peritoneal dialysis and renal transplant recipients) were recruited from 17 sites in England from July 2012 to October 2018. Physical activity was evaluated using the General Practice Physical Activity Questionnaire. Self-reported cardiorespiratory fitness, self-efficacy and stage of change were also assessed. Binominal generalized linear mutually adjusted models were conducted to explore the associations between physical activity and correlate variables. This cross-sectional observational multi-centre study was registered retrospectively as ISRCTN87066351 (October 2015). RESULTS: The prevalence of physical activity (6-34%) was low and worsened with disease progression. Being older, female and having a greater number of comorbidities were associated with greater odds of being physically inactive. Higher haemoglobin, cardiorespiratory fitness and self-efficacy levels were associated with increased odds of being active. Neither ethnicity nor smoking history had any effect on physical activity. CONCLUSIONS: Levels of physical inactivity are high across all stages of CKD. The identification of stage-specific correlates of physical activity may help to prioritize factors in target groups of kidney patients and improve the development and improvement of public health interventions.

Muscle power and physical dysfunction: A model for tailoring rehabilitation in chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is characterized by adverse physical function. Mechanical muscle power describes the product of muscular force and velocity of contraction. In CKD, the role of mechanical muscle power is poorly understood and often overlooked as a target in rehabilitation. The aims of this study were to investigate the association of mechanical power with the ability to complete activities of daily living and physical performance. METHOD: Mechanical muscle power was estimated using the sit-to-stand-5 test. Legs lean mass was derived using bioelectrical impedance analysis. Physical performance was assessed using gait speed and 'timed-up-and-go' (TUAG) tests. Self-reported activities of daily living (ADLs) were assessed via the Duke Activity Status Index. Balance and postural stability (postural sway and velocity) was assessed using a FysioMeter. Sex-specific tertiles were used to determine low levels of power. RESULTS: One hundred and two non-dialysis CKD participants were included (age: 62.0 (±14.1) years, n = 49 males (48%), eGFR: 38.0 (±21.5) ml/min/1.73m2 ). The mean relative power was 3.1 (±1.5) W/kg in females and 3.3 (±1.3) W/kg in males. Low relative power was found in 34% of patients. Relative power was an independent predictor of ADLs (ß = .413, p = .004), and TUAG (ß = -.719, p < .001) and gait speed (ß = .404, p = .003) performance. Skeletal muscle mass was not associated with any outcomes. CONCLUSION: Knowledge of the factors that mediate physical function impairment is crucial for developing effective interventions. Incorporation of power-based training focusing primarily on movement velocity may present the best strategy for improving physical function in CKD, above those that focus on increasing muscle mass.

Determinants of patient activation and its association with cardiovascular disease risk in chronic kidney disease: A cross-sectional study.

BACKGROUND: Patient activation describes the knowledge, skills and confidence in managing one's own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Patients with non-dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK. OUTCOME MEASURES: Patient activation was measured using the PAM-13. Demographic and health-related variables, self-reported symptom burden, health-related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia. RESULTS: 743 patients were included (eGFR: 32.3 (SD 17.1) mL/min/1.73 m2 , age 67.8 (SD 13.9) years, 68% male). The mean PAM score was 55.1 (SD 14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P = .004), greater number of comorbidities (P = .026) and lower haemoglobin (P = .025). Patients with low activation had a 17% greater number of CVD risk factors (P < .001). Risk factors in those with low activation were being older (P < .001) and having diabetes (P < .001). CONCLUSION: This study showed that only a minority of CKD patients are activated for self-management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation. PATIENT OR PUBLIC CONTRIBUTION: Patients were involved in the design of main study.

Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population.

BACKGROUND: Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. METHODS: Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. RESULTS: In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was 'feeling tired'; and 4) being female independently increased the likelihood of reporting more symptoms. CONCLUSIONS: Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. TRIAL REGISTRATION: The study was registered prospectively as ISRCTN11596292 .

Utility of Ultrasound as a Valid and Accurate Diagnostic Tool for Sarcopenia: Sex-Specific Cutoff Values in Chronic Kidney Disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) have aberrant changes in body composition, including low skeletal muscle mass, a feature of "sarcopenia." The measurement of the (quadriceps) rectus femoris (RF) cross-sectional area (CSA) is widely used as a marker of muscle size. Cutoff values are needed to help discriminate the condition of an individual's muscle (eg, presence of sarcopenia) quickly and accurately. This could help distinguish those at greater risk and aid in targeted treatment programs. METHODS: Transverse images of the RF were obtained by B-mode 2-dimensional ultrasound imaging. Sarcopenic levels of muscle mass were defined by established criteria (1, appendicular skeletal muscle mass [ASM]; 2, ASM/height2 ; and 3, ASM/body mass index) based on the ASM and total muscle mass measured by a bioelectrical impedance analysis. The discriminative power of RF-CSA was assessed by receiver operating characteristic curves, and optimal cutoffs were determined by the maximum Youden index (J). RESULTS: One hundred thirteen patients with CKD (mean age [SD], 62.0 [14.1] years; 48% male; estimated glomerular filtration rate, 38.0 [21.5] mL/min/1.73m2 ) were included. The RF-CSA was a moderate predictor of ASM (R2 = 0.426; P < .001) and total muscle mass (R2 = 0.438; P < .001). With a maximum J of 0.47, in male patients, an RF-CSA cutoff of less than 8.9 cm2 was deemed an appropriate cutoff for detecting sarcopenic muscle mass. In female patients, an RF-CSA cutoff of less than 5.7 cm2 was calculated on the basis of ASM/height2 (J = 0.71). CONCLUSIONS: Ultrasound may provide a low-cost and simple means to diagnose sarcopenia in patients with CKD. This would allow for early management and timely intervention to help mitigate the effects in this group.

Characteristics of effective home-based resistance training in patients with noncommunicable chronic diseases: a systematic scoping review of randomised controlled trials.

Skeletal muscle atrophy, dysfunction, and weakness are consequences of noncommunicable diseases which result in exercise and functional limitations which contribute to poor quality of life and increased mortality. Home-based resistance training may promote skeletal muscle health. Electronic-based systematic searches were performed identifying randomised controlled trials utilising home-based resistance training in patients with noncommunicable diseases defined as cancer, cardiovascular disease, diabetes mellitus (type 1 and 2), chronic kidney disease (including dialysis), and chronic respiratory disease (asthma, chronic obstructive pulmonary disease, pulmonary hypertension). A comparator group was defined as one containing "non-exercise" or "usual care". Of the 239 studies identified (published between 1996 and 2020), 22 met the inclusion criteria. Sixteen studies contained an adjunct aerobic training component. Study designs and outcome measures showed large variation. Reporting of the principles of training applied within interventions was poor. Heterogeneity in study characteristics, and poor reporting of training characteristics, prevents formal recommendations for optimising home-based resistance training. However, home-based interventions are less resource-intensive than supervised programmes and appear to have the ability to improve or preserve pertinent outcomes such as strength, functional ability, and quality of life; potentially reducing the risk of mortality in patients with chronic disease.

Quantitative Muscle Ultrasonography Using 2D Textural Analysis: A Novel Approach to Assess Skeletal Muscle Structure and Quality in Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by progressive reductions in skeletal muscle function and size. The concept of muscle quality is increasingly being used to assess muscle health, although the best means of assessment remains unidentified. The use of muscle echogenicity is limited by an inability to be compared across devices. Gray level of co-occurrence matrix (GLCM), a form of image texture analysis, may provide a measure of muscle quality, robust to scanner settings. This study aimed to identify GLCM values from skeletal muscle images in CKD and investigate their association with physical performance and strength (a surrogate of muscle function). Transverse images of the rectus femoris muscle were obtained using B-mode 2D ultrasound imaging. Texture analysis (GLCM) was performed using ImageJ. Five different GLCM features were quantified: energy or angular second moment (ASM), entropy, homogeneity, or inverse difference moment (IDM), correlation, and contrast. Physical function and strength were assessed using tests of handgrip strength, sit to stand-60, gait speed, incremental shuttle walk test, and timed up-and-go. Correlation coefficients between GLCM indices were compared to each objective functional measure. A total of 90 CKD patients (age 64.6 (10.9) years, 44% male, eGFR 33.8 (15.7) mL/minutes/1.73 m2) were included. Better muscle function was largely associated with those values suggestive of greater image texture homogeneity (i.e., greater ASM, correlation, and IDM, lower entropy and contrast). Entropy showed the greatest association across all the functional assessments (r = -.177). All GLCM parameters, a form of higher-order texture analysis, were associated with muscle function, although the largest association as seen with image entropy. Image homogeneity likely indicates lower muscle infiltration of fat and fibrosis. Texture analysis may provide a novel indicator of muscle quality that is robust to changes in scanner settings. Further research is needed to substantiate our findings.

Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min-1·1.73 m-2 (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min-1·1.73 m-2, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min-1·1.73 m-2) completed 20 min of walking at 60-70% peak O2 consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (P = 0.001) and nonclassical (P = 0.002) monocyte subset proportions but decreased the intermediate subset (P < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups (P = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).

Advances in exercise therapy in predialysis chronic kidney disease, hemodialysis, peritoneal dialysis, and kidney transplantation.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is characterized by poor levels of physical activity which contribute to increased morbidity across the disease trajectory. The short nature, small samples, and poor methodology across most studies have failed to translate the role of exercise in CKD into its adoption as a frontline adjunct therapeutic option. This review focuses on recent advances surrounding the benefits of exercise interventions across the CKD spectrum. RECENT FINDINGS: Key recent advances in exercise studies have focused on the efficacy of novel intervention strategies across the CKD spectrum. These include high-intensity interval training, virtual reality gaming, intradialytic yoga, electrical stimulation of muscles, blood flow restriction training, and protocols combining exercise with nutritional supplementation. Research is also beginning to explore the role of prehabilitation for patients prior to dialysis and kidney transplantation. SUMMARY: Studies continue to demonstrate wide-ranging benefits of exercise across CKD; however, implementation of exercise remains scarce. Future research needs include evaluating the efficacy of larger and/or more comprehensive interventions on clinically important outcomes. It is hoped with increasing global evidence, high-quality clinical studies, and sustained clinician and patient engagement, exercise programs will become better prioritized in the nephrology field.

Identification of the most clinically useful skeletal muscle mass indices pertinent to sarcopenia and physical performance in chronic kidney disease.

AIM: Patients with chronic kidney disease (CKD) are characterised by low skeletal muscle mass that negatively impacts physical performance. Operational definitions of 'low muscle mass' are inconsistent, and it is unknown how different skeletal muscle mass indices affect the relationship between muscle mass and physical function. METHODS: Appendicular skeletal muscle mass (ASM) was measured by dual-energy X-ray absorptiometry in 72 CKD patients. Along with crude ASM, alternative muscle indices were calculated adjusting for height, height-squared, body mass, and BMI. Physical performance was assessed by handgrip strength, sit-to-stand tests, gait speed, the incremental shuttle walk test and 'Short Physical Performance Battery'. RESULTS: Prevalence of 'low muscle mass' ranged from 26% to 35% of patients depending on the criteria used. The relationship between muscle mass indices and physical function differed for each criteria. Using average coefficients, the association with overall physical function and muscle indices were as follows: crude ASM (r = .258), ASM/height (r = .249), ASM/height-squared (r = .332), ASM/body mass (r = .249) and ASM/BMI (r = .206). Muscle adjusted for markers of adiposity (ASM/body fat %, r = .266; ASM/fat mass, r = .338) provided the best overall associations with physical function. CONCLUSION: The use of alternative muscle mass indices provide different estimates of 'low muscle mass' prevalence, and the strongest (and most useful definition in regard to functional status) involves adjustment for either total or relative body fat. ASM adjusted for adiposity may be physiologically and clinically more relevant in patients with renal disease.