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1.
Ultrason Imaging ; : 1617346241255879, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807343

RESUMO

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.

2.
Kidney Int Rep ; 8(8): 1496-1505, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37547514

RESUMO

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

3.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37046990

RESUMO

Chronic Kidney Disease (CKD) is a global health burden with high mortality and health costs. CKD patients exhibit lower cardiorespiratory and muscular fitness, strongly associated with morbidity/mortality, which is exacerbated when they reach the need for renal replacement therapies (RRT). Muscle wasting in CKD has been associated with an inflammatory/oxidative status affecting the resident cells' microenvironment, decreasing repair capacity and leading to atrophy. Exercise may help counteracting such effects; however, the molecular mechanisms remain uncertain. Thus, trying to pinpoint and understand these mechanisms is of particular interest. This review will start with a general background about myogenesis, followed by an overview of the impact of redox imbalance as a mechanism of muscle wasting in CKD, with focus on the modulatory effect of exercise on the skeletal muscle microenvironment.


Assuntos
Músculo Esquelético , Insuficiência Renal Crônica , Humanos , Músculo Esquelético/metabolismo , Insuficiência Renal Crônica/metabolismo , Atrofia Muscular/metabolismo , Oxirredução , Exercício Físico
4.
BMC Nephrol ; 23(1): 268, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896969

RESUMO

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.


Assuntos
Anemia , Deficiências de Ferro , Insuficiência Renal Crônica , Suplementos Nutricionais , Método Duplo-Cego , Tolerância ao Exercício , Fadiga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento
5.
Nutrients ; 14(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35565785

RESUMO

This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible. Trials were restricted to those which had reported measures of sarcopenia. Primary outcome measures were hand grip strength and sit-to-stand tests. Sixty-four trials were eligible (with nineteen being included in meta-analyses). Synthesised data indicated that intradialytic exercise increased hand grip strength (standardised mean difference, 0.58; 0.24 to 0.91; p = 0.0007; I2 = 40%), and sit-to-stand (STS) 60 score (mean difference, 3.74 repetitions; 2.35 to 5.14; p < 0.001; I2 = 0%). Intradialytic exercise alone, and protein supplementation alone, resulted in no statistically significant change in STS5 (−0.78 s; −1.86 to 0.30; p = 0.16; I2 = 0%), and STS30 (MD, 0.97 repetitions; −0.16 to 2.10; p = 0.09; I2 = 0%) performance, respectively. For secondary outcomes, L-carnitine and nandrolone-decanoate resulted in significant increases in muscle quantity in the dialysis population. Intradialytic exercise modifies measures of sarcopenia in the haemodialysis population; however, the majority of trials were low in quality. There is limited evidence for efficacious interventions in the peritoneal dialysis and transplant recipient populations.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Sarcopenia , Adulto , Feminino , Força da Mão , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Diálise Renal/efeitos adversos , Sarcopenia/etiologia , Sarcopenia/terapia
7.
J Cachexia Sarcopenia Muscle ; 13(2): 1238-1249, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35029054

RESUMO

BACKGROUND: Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy-based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo. METHODS: Here, we performed a systematic characterization of CKD derived muscle cells (CKD; n = 10; age: 54.40 ± 15.53 years; eGFR: 22.25 ± 13.22 ml/min/1.73 m2 ) in comparison with matched controls (CON; n = 10; age: 58.66 ± 14.74 years; eGFR: 85.81 ± 8.09 ml/min/1.73 m2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF-1 in order to investigate any differences in anabolic resistance. RESULTS: Harvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation (P = 0.044) alongside elevated expression of both TRIM63 (2.28-fold higher, P = 0.054) and fbox32 (6.4-fold higher, P < 0.001) in comparison with CONs. No differences were noted in rates of protein synthesis under basal conditions (P > 0.05); however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF-1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P < 0.001; 100 nM: P < 0.001). CONCLUSIONS: In summary, we report for the first time that HDMCs isolated from people suffering from CKD display key hallmarks of the well documented in vivo phenotype. Not only do these findings provide further mechanistic insight into CKD specific cachexia, but they also demonstrate this is a reliable and suitable model in which to perform targeted experiments to begin to develop novel therapeutic strategies targeting the CKD associated decline in skeletal muscle mass and function.


Assuntos
Caquexia , Insuficiência Renal Crônica , Animais , Caquexia/metabolismo , Humanos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Insuficiência Renal Crônica/metabolismo
8.
Nephrol Dial Transplant ; 37(5): 860-868, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35090033

RESUMO

BACKGROUND: People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. METHODS: This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n = 84, n = 43 males) and non-CKD controls (n = 26, n = 17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n = 21) or combined (CE, n = 20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. RESULTS: Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P = 0.01), Rectus femoris-cross sectional area (P = 0.002) and incremental shuttle walk test performance (P < 0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P = 0.006) and hand grip strength (P = 0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P = 0.02). Changes in inflammation were not associated with changes in physical performance. CONCLUSIONS: Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Exercício Físico , Terapia por Exercício , Feminino , Força da Mão , Humanos , Inflamação/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Atrofia Muscular/complicações , Miostatina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
9.
JCSM Rapid Commun ; 5(1): 3-9, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34541518

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The role of skeletal muscle mass in modulating immune response is well documented. Whilst obesity is well established as a key factor in COVID-19 and outcome, no study has examined the influence of both sarcopenia (low muscle mass) and obesity, termed 'sarcopenic obesity' on the risk of severe COVID-19. Methods: This study uses data from UK Biobank. Probable sarcopenia was defined as low handgrip strength. Sarcopenic obesity was mutually exclusively defined as the presence of obesity and low muscle mass [based on two established criteria: appendicular lean mass (ALM) adjusted for either (i) height or (ii) body mass index]. Severe COVID-19 was defined by a positive severe acute respiratory syndrome coronavirus 2 test result in a hospital setting and/or death with a primary cause reported as COVID-19. Fully adjusted logistic regression models were used to analyse the associations between sarcopenic status and severe COVID-19. This work was conducted under UK Biobank Application Number 52553. Results: We analysed data from 490 301 UK Biobank participants (median age 70.0 years, 46% male); 2203 (0.4%) had severe COVID-19. Individuals with probable sarcopenia were 64% more likely to have had severe COVID-19 (odds ratio 1.638; P < 0.001). Obesity increased the likelihood of severe COVID-19 by 76% (P < 0.001). Using either ALM index or ALM/body mass index to define low muscle mass, those with sarcopenic obesity were 2.6 times more likely to have severe COVID-19 (odds ratio 2.619; P < 0.001). Sarcopenia alone did not increase the risk of COVID-19. Conclusions: Sarcopenic obesity may increase the risk of severe COVID-19, over that of obesity alone. The mechanisms for this are complex but could be a result of a reduction in respiratory functioning, immune response, and ability to respond to metabolic stress.

10.
J Ren Nutr ; 32(4): 371-381, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34294555

RESUMO

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.


Assuntos
Força da Mão , Insuficiência Renal Crônica , Estudos Epidemiológicos , Humanos , Insuficiência Renal Crônica/epidemiologia
11.
Nephrology (Carlton) ; 26(10): 790-797, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34218477

RESUMO

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.


Assuntos
Atividades Cotidianas , Contração Muscular , Força Muscular , Músculo Esquelético/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Composição Corporal , Ensaios Clínicos como Assunto , Estudos Transversais , Impedância Elétrica , Feminino , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Recuperação de Função Fisiológica , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/reabilitação , Inquéritos e Questionários , Resultado do Tratamento , Velocidade de Caminhada
12.
J Cachexia Sarcopenia Muscle ; 12(3): 586-598, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33949807

RESUMO

BACKGROUND: Sarcopenia, a degenerative and generalized skeletal muscle disorder involving the loss of muscle function and mass, is an under-recognized problem in clinical practice, particularly in chronic kidney disease (CKD). We aimed to investigate the prevalence of sarcopenia in individuals with CKD, its risk factors, and its association with all-cause mortality and progression to end-stage renal disease (ESRD). METHODS: UK Biobank participants were grouped according to the presence of CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and as having probable (low handgrip strength), confirmed (plus low muscle mass), and severe sarcopenia (plus poor physical performance) based on the 2019 European Working Group of Sarcopenia in Older People and Foundation for the National Institutes of Health criteria. Risk factors were explored using logistic regression analysis. Survival models were applied to estimate risk of mortality and ESRD. RESULTS: A total of 428 320 participants, of which 8767 individuals with CKD (46% male, aged 62.8 (standard deviation 6.8) years, median estimated glomerular filtration rate 54.5 (interquartile range 49.0-57.7) mL/min/1.72 m2 ) were included. Probable sarcopenia was present in 9.7% of individuals with CKD compared with 5.0% in those without (P < 0.001). Sarcopenia was associated with being older; inflammation; poorer renal function; and lower serum albumin, total testosterone, and haemoglobin. The largest risk factors for sarcopenia were having three or more comorbidities (odds ratio: 2.30; 95% confidence interval: 1.62 to 3.29; P < 0.001) and physical inactivity: participants in the highest quartile of weekly activity were 43% less likely to have sarcopenia compared to the lowest quartile (odds ratio: 0.57; 0.42 to 0.76; P < 0.001). Participants with CKD and sarcopenia had a 33% (7% to 66%; P = 0.011) higher hazard of mortality compared with individuals without. Sarcopenic CKD individuals had a 10 year survival probability of 0.85 (0.82 to 0.88) compared with 0.89 (0.88 to 0.30) in those without sarcopenia, an absolute difference of 4%. Those with sarcopenia were twice as likely to develop ESRD (hazard ratio: 1.98; 1.45 to 2.70; P < 0.001). CONCLUSIONS: Participants with reduced kidney function are at an increased risk of premature mortality. The presence of sarcopenia increases the risk of mortality and ESRD. Appropriate measurement of sarcopenia should be used to identify at-risk individuals. Interventions such as physical activity should be encouraged to mitigate sarcopenia.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Sarcopenia , Idoso , Bancos de Espécimes Biológicos , Feminino , Força da Mão , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Reino Unido/epidemiologia
13.
Ultrason Imaging ; 43(3): 139-148, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33853450

RESUMO

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.


Assuntos
Força da Mão , Insuficiência Renal Crônica , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Insuficiência Renal Crônica/diagnóstico por imagem , Ultrassonografia
14.
J Steroid Biochem Mol Biol ; 210: 105861, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675951

RESUMO

BACKGROUND: Evidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. METHODS: This is a secondary cross-sectional analysis of previously published interventional study, with in vitro follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3 mL/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n = 20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. RESULTS: In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with V̇O2Peak was seen with total vitamin D (25OHD). in vitro, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. CONCLUSIONS: Vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.


Assuntos
Tolerância ao Exercício/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Idoso , Calcitonina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estudos Transversais , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Insuficiência Renal Crônica/complicações , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/etiologia
15.
BMC Nephrol ; 21(1): 334, 2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770949

RESUMO

BACKGROUND: Chronic Kidney Disease (CKD) patients frequently develop life-impairing bone mineral disorders. Despite the reported impact of exercise on bone health, systematic reviews of the evidence are lacking. This review examines the association of both physical activity (PA) and the effects of different exercise interventions with bone outcomes in CKD. METHODS: English-language publications in EBSCO, Web of Science and Scopus were searched up to May 2019, from which observational and experimental studies examining the relation between PA and the effect of regular exercise on bone-imaging or -outcomes in CKD stage 3-5 adults were included. All data were extracted and recorded using a spreadsheet by two review authors. The evidence quality was rated using the Cochrane risk of bias tool and a modified Newcastle-Ottawa scale. RESULTS: Six observational (4 cross-sectional, 2 longitudinal) and seven experimental (2 aerobic-, 5 resistance-exercise trials) studies were included, with an overall sample size of 367 and 215 patients, respectively. Judged risk of bias was low and unclear in most observational and experimental studies, respectively. PA was positively associated with bone mineral density at lumbar spine, femoral neck and total body, but not with bone biomarkers. Resistance exercise seems to improve bone mass at femoral neck and proximal femur, with improved bone formation and inhibited bone resorption observed, despite the inconsistency of results amongst different studies. CONCLUSIONS: There is partial evidence supporting (i) a positive relation of PA and bone outcomes, and (ii) positive effects of resistance exercise on bone health in CKD. Prospective population studies and long-term RCT trials exploring different exercise modalities measuring bone-related parameters as endpoint are currently lacking.


Assuntos
Densidade Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/reabilitação , Terapia por Exercício , Exercício Físico , Insuficiência Renal Crônica/reabilitação , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento Resistido
16.
Kidney Res Clin Pract ; 39(3): 305-317, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32550710

RESUMO

BACKGROUND: Chronic kidney disease (CKD) patients have poor cardiorespiratory fitness. Although cardiopulmonary exercise testing (CPET) is a universal assessment of cardiorespiratory fitness, values taken at 'peak' effort are strongly influenced by motivation and the choice of test endpoint. The oxygen uptake efficiency slope (OUES) integrates cardiovascular, musculoskeletal, and respiratory function into a single index to provide a more pragmatic and safer alternative to maximal testing. No research has explored whether exercise can improve the OUES in CKD patients. METHODS: Thirty-two patients with non-dialysis CKD were recruited into a 12-week exercise program consisting of mixed aerobic and resistance training three times a week. CPET was conducted at baseline, and then, following a 6-week control period, at pre- and post-exercise intervention. Direct measurements of oxygen consumption (V̇O2) and ventilatory parameters were collected. The OUES was calculated as the relationship between V̇O2 and the log10 of minute ventilation (V̇E). RESULTS: No changes were observed in any variable during the control period, although modest increases in V̇O2peak were observed. No meaningful changes were observed as a result of exercise in any cardiorespiratory value obtained. The OUES calculated at 100%, 90%, 75%, and 50% of exercise duration did not change significantly after 12 weeks of exercise training. CONCLUSION: Our results show that 12 weeks of exercise training had no beneficial effects on the OUES, which supports the modest change observed in V̇O2peak. The lack of change in the OUES and other parameters could indicate a dysfunctional cardiorespiratory response to exercise in patients with CKD, likely mediated by dysfunctional peripheral metabolic mechanisms.

17.
FASEB J ; 34(1): 1755-1767, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914685

RESUMO

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.


Assuntos
Exercício Físico/fisiologia , Mitocôndrias Musculares/fisiologia , Músculo Esquelético/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Transversais , Feminino , Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Doenças Musculares/metabolismo , Doenças Musculares/fisiopatologia , Estudos Observacionais como Assunto , Biogênese de Organelas , Músculo Quadríceps/metabolismo , Músculo Quadríceps/fisiologia , Treinamento Resistido/métodos
18.
Nephrol Dial Transplant ; 35(9): 1469-1478, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603229

RESUMO

Skeletal muscle wasting is a common complication of chronic kidney disease (CKD), characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. Evidence suggests that increasing skeletal muscle mass improves outcomes in CKD, making this a clinically important research focus. Despite extensive research, the pathogenesis of skeletal muscle wasting is not completely understood. It is widely recognized that microRNAs (miRNAs), a family of short non-coding RNAs, are pivotal in the regulation of skeletal muscle homoeostasis, with significant roles in regulating muscle growth, regeneration and metabolism. The abnormal expression of miRNAs in skeletal muscle during disease has been well described in cellular and animal models of muscle atrophy, and in recent years, the involvement of miRNAs in the regulation of muscle atrophy in CKD has been demonstrated. As this exciting field evolves, there is emerging evidence for the involvement of miRNAs in a beneficial crosstalk system between skeletal muscle and other organs that may potentially limit the progression of CKD. In this article, we describe the pathophysiological mechanisms of muscle wasting and explore the contribution of miRNAs to the development of muscle wasting in CKD. We also discuss advances in our understanding of miRNAs in muscle-organ crosstalk and summarize miRNA-based therapeutics currently in clinical trials.


Assuntos
MicroRNAs/genética , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Insuficiência Renal Crônica/complicações , Animais , Homeostase , Humanos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Insuficiência Renal Crônica/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-30838203

RESUMO

Tissue engineered skeletal muscle allows investigation of the cellular and molecular mechanisms that regulate skeletal muscle pathology. The fabricated model must resemble characteristics of in vivo tissue and incorporate cost-effective and high content primary human tissue. Current models are limited by low throughput due to the complexities associated with recruiting tissue donors, donor specific variations, as well as cellular senescence associated with passaging. This research presents a method using fused deposition modeling (FDM) and laser sintering (LS) 3D printing to generate reproducible and scalable tissue engineered primary human muscle, possessing aligned mature myotubes reminiscent of in vivo tissue. Many existing models are bespoke causing variability when translated between laboratories. To this end, a scalable model has been developed (25-500 µL construct volumes) allowing fabrication of mature primary human skeletal muscle. This research provides a strategy to overcome limited biopsy cell numbers, enabling high throughput screening of functional human tissue.

20.
J Cell Biochem ; 119(7): 6094-6103, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29574938

RESUMO

Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (Rv E1 ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, Rv E1 attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1ß in C2C12 skeletal muscle myotubes. Findings at the molecular level were transferred into similar changes in extracellular protein levels of the corresponding genes with the greatest attenuation being noted in IL-6 protein concentrations. Rv E1 instigated beneficial morphological changes through the prevention of LPS induced skeletal muscle atrophy, in tandem with attenuation of the LPS induced reduction in contractile force in tissue engineered skeletal muscle. These findings demonstrate, in our model of endotoxin induced inflammation in skeletal muscle, that Rv E1 has pro-resolving properties in this cell type. Our data provides rationale for further investigation into the mechanistic action of Rv E1 in skeletal muscle, with the vision of having potential benefits for the prevention/resolution of in-vivo skeletal muscle atrophy.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Animais , Células Cultivadas , Ácido Eicosapentaenoico/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo
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