Combined low-carbohydrate diet and long-term exercise in hypoxia in type 2 diabetes: A randomized controlled trial protocol to assess glycemic control, cardiovascular risk factors and body composition.

Background: Cardiovascular disease is the leading cause of mortality associated with diabetes, which is characterized by chronic hyperglycemia. Low-carbohydrate diet has gained popularity as an intervention in patients with type 2 diabetes mellitus, acting to improve glycemic profile and serum lipids. In its turn, exercise in hypoxia induces specific adaptations, mostly modulated via hypoxia-induced transcription factor signaling cascade, which increases with exposure to altitude, and promotes angiogenesis, glycogen supply, glucose tolerance, and raises GLUT-4 expression. Aim: Given that hyperglycemia decreases HIF-1α and it is better controlled when following a low-carbohydrate diet, this study aims to examine the hypothesis that a combination of both low-carbohydrate diet and chronic exercise in hypoxia in type 2 diabetes mellitus is associated with improved glycemic control and cardiovascular parameters, whose protocol is described. Methods: Patients with type 2 diabetes mellitus (n = 48) will be recruited and randomized into one of the three groups: (a) Control group: Control diet (low-fat and moderate-carbohydrate diet) + exercise in normoxia; (2) exercise in hypoxia group: Control diet + exercise in hypoxia; (3) intervention group: Low-carbohydrate diet (low-carbohydrate and high-fat diet) + exercise in hypoxia. Before and after 8 weeks of interventions, cardiopulmonary tests (Bruce protocol), body composition and blood pressure will be evaluated. Blood samples will be collected to measure hypoxia-induced transcription factor, C-reactive protein, glycemic and lipid profiles. Summary: This will be the first trial to examine the isolated and combined effect of chronic exercise in hypoxia and low-carbohydrate diet in type 2 diabetes mellitus. This trial will help to fill a significant research gap, guide future research and contribute to the combined nutrition and exercise approach to type 2 diabetes mellitus.

Novel Approach to Intradialytic Progressive Resistance Exercise Training.

Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.

Effects of Exercise on Inflammatory Markers in Individuals with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Individuals with chronic kidney disease (CKD) have a systemic inflammatory state. We assessed the effects of exercise on inflammatory markers in individuals with CKD. An electronic search was conducted, including MEDLINE. Experimental clinical trials that investigated the effects of exercise on inflammatory markers in individuals with CKD at all stages were included. Meta-analyses were conducted using the random-effects model and standard mean difference (SMD). Subgroup analyses were performed for resistance, aerobic, and combined exercise interventions. Twenty-nine studies were included in the meta-analyses. Exercise interventions showed significant reductions in C-reactive protein (CRP) (SMD: -0.23; 95% CI: -0.39 to -0.06), interleukin (IL)-6 (SMD: -0.35; 95% CI: -0.57, -0.14), and tumor necrosis factor-alpha (TNF-α) (SMD: -0.63, 95% CI: -1.01, -0.25) when compared with the controls. IL-10 levels significantly increased (SMD: 0.66, 95% CI: 0.09, 1.23) with exercise interventions. Resistance interventions significantly decreased CRP (SMD: -0.39, 95% CI: -0.69, -0.09) and TNF-α (SMD: -0.72, 95% CI: -1.20, -0.23) levels, while increasing IL-10 levels (SMD: 0.57, 95% CI: 0.04, 1.09). Aerobic interventions only significantly reduced IL-6 levels (SMD: -0.26, 95% CI: -0.51, -0.01). No significant changes in any inflammatory markers were observed with combined exercise interventions. Exercise interventions are effective as an anti-inflammatory therapy in individuals with CKD compared to usual care control groups. Resistance interventions seem to promote greater anti-inflammatory effects.

Intradialytic resistance training for short daily hemodialysis patients as part of the clinical routine: a quasi-experimental study.

Background and purpose: Hemodialysis patients have chronic systemic inflammation, musculoskeletal impairments, and body composition changes from several factors and exercise may attenuate. We evaluated the effects of an intradialytic resistance training program on body composition, physical function, and inflammatory markers in patients under short daily hemodialysis treatment. Materials and methods: A quasi-experimental study in clinical routine was conducted over eight months. Measures of physical function (handgrip strength, five-time sit-to-stand, timed-up and go, and gait speed), body composition (by bioelectrical impedance), and inflammatory markers (interleukin [IL]-1 beta, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-α) were assessed at baseline as well as at four and eight months past continued intervention. Patients underwent two intradialytic resistance training sessions per week supervised by exercise professionals. Results: A total of 18 patients (62 ± 14 years; 55.6% ≥ 60 years; 44% female) were included. Significant increases in body mass index and basal metabolic rate were found at four and eight months compared to baseline. For physical function, timed-up and go performance improved at four and eight months compared to baseline. The other body composition and physical function measures, as well as all inflammatory markers, did not significantly change over time. Conclusion: A supervised intradialytic resistance training program for patients on short daily hemodialysis treatment, as part of the clinical routine, may induce modest changes in body mass index, basal metabolic rate, and timed-up and go performance.

The Potential Modulatory Effects of Exercise on Skeletal Muscle Redox Status in Chronic Kidney Disease.

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.

Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits.

Increasing evidence indicates that exercise has beneficial effects on chronic inflammation, cardiorespiratory function, muscle and bone strength and metabolic markers in adults with chronic kidney disease (CKD), kidney failure or kidney transplants. However, the mechanisms that underlie these benefits have received little attention, and the available clinical evidence is mainly from small, short-duration (<12 weeks) exercise intervention studies. The available data, mainly from patients with CKD or on dialysis, suggest that exercise-mediated shifts towards a less inflammatory immune cell profile, enhanced activity of the NRF2 pathway and reduced monocyte infiltration into adipose tissue may underlie improvements in inflammatory biomarkers. Exercise-mediated increases in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise stimulates an anabolic response in skeletal muscle in CKD, but increases in mitochondrial mass and satellite cell activation seem to be impaired in this population. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation and improvements in the levels of the bone-derived hormones klotho and fibroblast growth factor 23 (FGF23). Longer duration studies with larger sample sizes are needed to confirm these mechanisms in CKD, kidney failure and kidney transplant populations and provide evidence for targeted exercise interventions.

How is exercise being prescribed for patients on hemodialysis? A scoping review.

BACKGROUND: Exercise is important for patients on hemodialysis, but details and descriptions on how it is prescribed are lacking. We reviewed the existing literature and described how exercise is being prescribed for patients on hemodialysis. METHODS: A scoping review according to the JBI and PRISMA-ScR guidelines was conducted. MEDLINE, EMBASE and other databases were searched from inception until December 2021. Websites, books, and guidelines were also searched. We included evidence from patients on hemodialysis, describing exercise protocols, in all settings and designs. RESULTS: Two hundred and eighty-five studies were included, yielding 327 exercise protocols. Aerobic (38.8%) and strength (21.4%) were the most prescribed exercise types. Exercise was mainly prescribed during dialysis (71.0%) and delivered within the first half of the session (94.6%). Although 33.3% of the exercise protocols did not report whether there was supervision or not, those that did were mostly delivered by physiotherapists (20.5%) and exercise physiologists (17.4%). The most followed exercise training principles were type (99.0%) and frequency (93.2%), whereas progression was adopted in 40.7% protocols. The most prescribed frequency and duration were three times/week (79.9%) and 30-60-min (69.2%) sessions, respectively. Exercise intensity was predominantly prescribed in moderate cut-offs (72.3%), mostly assessed by subjective methods (47.5%). CONCLUSIONS: Aerobic and strength were the most prescribed exercise types, mainly during dialysis. Interventions were mostly supervised by physiotherapists and exercise physiologists. Future exercise protocols for patients on hemodialysis should adopt recommended exercise principles, especially with systematic progression.

Prevalence of low bone mineral density (T-score ≤ - 2.5) in the whole spectrum of chronic kidney disease: a systematic review and meta-analysis.

The prevalence of low bone mineral density (LBMD) in people with chronic kidney disease (CKD) remains unknown. We identified a high prevalence of LBMD in CKD population. Thus, public health strategies should include efforts to prevent, early detect, and manage LBMD in CKD patients, especially in patients undergoing kidney replacement therapy. Mineral and bone disorders are common among patients with CKD, which affects bone mineral density. We conducted a systematic review and meta-analysis to estimate the prevalence of low bone mineral density (LBMD) in adults with CKD. We searched MEDLINE, EMBASE, Web of Science, CINAHL, and LILACS databases from inception to February 2021. Observational studies that reported the prevalence of LBMD in adults with CKD stages 3a-5D were included. The LBMD was defined according to the World Health Organization criterion (T-score ≤ - 2.5). Random-effect model meta-analyses were used to estimate the pooled prevalence of LBMD. Meta-regressions and subgroup analyses were conducted for stages of CKD, dialysis modality, gender, bone sites and morphology, and geographical region. This study was registered in PROSPERO, number CRD42020211077. One-hundred and fifty-three studies with 78,092 patients were included. The pooled global prevalence of LBMD in CKD was 24.5% (95% CI, 21.3 - 27.8%). Subgroup analyses indicated a higher prevalence of LBMD in dialysis patients (30%, 95% CI 25 - 35%) compared with non-dialysis CKD patients (12%, 95% CI 8 - 16%), cortical bone sites (28%, 95% CI 23 - 35%) relative to trabecular sites (19%, 95% CI 14 - 24%), while similar estimates in the European and the Asiatic continents (26%, 95% CI 21 - 30% vs 25%, 95% CI 21 - 29). The prevalence of LBMD in CKD patients is high, particularly in those undergoing dialysis and in cortical bone sites. Therefore, efforts to early diagnosis and management strategies should be implemented in clinical routine for an epidemiological control of LBMD in CKD patients.

Glittre activities of daily living test is reliable and valid in hemodialysis patients.

PURPOSE: To examine the validity, and the relative and absolute within-day reliability of the TGlittre in chronic kidney disease patients undergoing hemodialysis (HD). MATERIALS AND METHODS: Thirty HD patients (52 ± 12 years) undertook the TGlittre twice on a single day, in a cross-sectional design. For validation purposes, participants TGlittre performance and accelerometry-based physical activity were correlated. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC) were determined to assess within-day reliability. RESULTS: There was a moderate correlation between TGlittre performance and moderate to vigorous physical activity (r= -0.587; p= 0.001). The relative reliability of the test showed an ICC of 0.96. For the absolute reliability, the SEM was 13.05 s (0.22 min), and the MDC was 36.17 s (0.60 min). CONCLUSIONS: TGlittre performance is associated with moderate to vigorous physical activity in HD patients, highlighting that those with higher levels of physical activity are likely to perform better on the TGlittre. Additionally, TGlittre shows a good to excellent intra-rater reliability and a low SEM. An MDC value was established.Implications for rehabilitationPatients on hemodialysis have a low physical capacity and often struggle to simply complete their physical activities of daily living.The TGlittre is a tool for assessing functional capacity through completion of multiple physical activities of daily living and can be easily applied in a clinical setting.TGlittre is a valid test that elicit reliable physiological, hemodynamic, and physical performance responses in HD patients.

Implementing a resistance training programme for patients on short daily haemodialysis: A feasibility study.

BACKGROUND: Kidney failure patients receiving haemodialysis experience protein-energy wasting, muscle mass loss and physical function impairment. Intradialytic exercise interventions seem to modify these features, but they are often not implemented as a clinical routine. OBJECTIVE: To investigate the feasibility of implementing a supervised intradialytic resistance training programme as a clinical routine for patients receiving short daily haemodialysis. DESIGN: A prospective longitudinal study. PARTICIPANTS: Eighteen patients in a supervised intradialytic resistance training programme for 8 months. MEASUREMENTS: It consisted of a warm-up, lower- and upper-limb resistance exercises and a cool-down. Patients performed the resistance training during the first half of haemodialysis, twice a week, supervised by exercise physiologists and physiotherapists. The feasibility was assessed by the total and partial adherences, the reasons for refusing or for not exercising and the intradialytic complications. RESULTS: From a total of 953 potential exercise sessions, 759 were performed, with a 79.6% adherence rate. In the first 9 weeks, the adherence rate was 86.6% and the lowest rate was in the 19-27 weeks (73.5%). The main intradialytic complication during exercise sessions was hypotension (n = 31; 4.1%). The highest number of complications was reported during the first 9 weeks (n = 27; 9.1%). The main reasons for refusing or for not performing the intradialytic exercise sessions were clinical complications previous to exercise time (n = 63; 32.5%) and self-reported indisposition (n = 62; 32.0%). CONCLUSIONS: The intradialytic resistance training programme, supervised by exercise physiologists and physiotherapists, had very low complications, achieved a high long-term adherence rate and showed to be feasible as a clinical routine for patients receiving short daily haemodialysis.

Physical activity and the 'pediatric inactivity triad' in children living with chronic kidney disease: a narrative review.

The 'paediatric inactivity triad' (PIT) framework consists of three complex inter-related conditions that influence physical inactivity and related health risks. In those living with chronic kidney disease (CKD), a multi-factorial milieu of components likely confound the PIT elements, resulting in a cycle of decreased physical functioning and reduced physical activity. In this review, we explore and summarize previous research on each of the three principal PIT components (exercise deficit disorder, dynapenia, and physical illiteracy) in the pediatric CKD population. We found those living with CKD are significantly physically inactive compared to their peers. Physical inactivity occurs early in the disease process and progressively gets worse as disease burden increases. Although physical activity appears to increase post-transplantation, it remains lower compared to healthy controls. There is limited evidence on interventions to increase physical activity behaviour in this population, and those that have attempted have had negligible effects. Studies reported profound reductions in muscle strength, physical performance, and cardiorespiratory fitness. A small number of exercise-based interventions have shown favourable improvements in physical function and cardiorespiratory fitness, although small sample sizes and methodological issues preclude the generalization of findings. Physical activity must be adapted and individualized to the needs and goals of the children, particularly those with acute and chronic medical needs as is the case in CKD, and further work is needed to define optimal interventions across the life course in this population if we aim to prevent physical activity declining further.

Dietary Nitrate Supplementation Is Not Helpful for Endurance Performance at Simulated Altitude Even When Combined With Intermittent Normobaric Hypoxic Training.

Introduction: Training intensity and nutrition may influence adaptations to training performed in hypoxia and consequently performance outcomes at altitude. This study investigates if performance at simulated altitude is improved to a larger extent when high-intensity interval training is performed in normobaric hypoxia and if this is potentiated when combined with chronic dietary nitrate (NO3 -) supplementation. Methods: Thirty endurance-trained male participants were allocated to one of three groups: hypoxia (13% FiO2) + NO3 -; hypoxia + placebo; and normoxia (20.9% FiO2) + placebo. All performed 12 cycling sessions (eight sessions of 2*6 × 1 min at severe intensity with 1 min recovery and four sessions of 4*6*10 s all-out with 20 s recovery) during a 4-week period (three sessions/week) with supplementation administered 3-2.5 h before each session. An incremental exhaustion test, a severe intensity exercise bout to exhaustion (T lim) and a 3 min all-out test (3AOT) in hypoxia (FiO2 = 13%) with pulmonary oxygen uptake ( V ˙ O2), V ˙ O2 kinetics, and changes in vastus lateralis local O2 saturation (SmO2) measured were completed by each participant before and after training. Results: In all tests, performance improved to the same extent in hypoxia and normoxia, except for SmO2 after T lim (p = 0.04, d = 0.82) and 3AOT (p = 0.03, d = 1.43) which were lower in the two hypoxic groups compared with the normoxic one. Dietary NO3 - supplementation did not bring any additional benefits. Conclusion: Performance at simulated altitude was not improved to a larger extent when high-intensity interval training was undertaken in normobaric hypoxic conditions, when compared with normoxic training. Additionally, dietary NO3 - supplementation was ineffective in further enhancing endurance performance at simulated altitude.

Association between sarcopenia and clinical outcomes in chronic kidney disease patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Sarcopenia is a risk factor for adverse outcomes in older adults, but this has yet to be confirmed in chronic kidney disease (CKD). We conducted a systematic review to investigate the association between sarcopenia and its traits with mortality, hospitalization, and end-stage kidney disease (ESKD) progression in CKD patients. METHODS: Five electronic databases were searched, including MEDLINE and Embase. Observational cohort studies with CKD patients were included. The sarcopenia traits assessed were low muscle strength, low muscle mass, and low physical performance, as well as diagnosed sarcopenia (combined low muscle mass and low strength/performance). Hazard ratios (HR), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CI) were pooled using random-effect meta-analyses. RESULTS: From a total of 4922 screened studies, 50 (72,347 patients) were included in the review and 38 (59,070 patients) in the meta-analyses. Most of the included studies were in dialysis patients (n = 36, 72%). Pooled analyses showed that low muscle strength (15 studies; HR:1.99; 95%CI:1.65 to 2.41; I2:45%), low muscle mass (20 studies; HR:1.51; 95%CI:1.36 to 1.68; I2:26%) and low physical performance (five studies; HR:2.09; 95%CI:1.68 to 2.59; I2:0%) were associated with increased mortality risk in CKD patients. Diagnosed sarcopenia was also associated with the mortality risk in dialysis patients (eight studies; HR:1.87; 95%CI:1.35 to 2.59; I2:40%). On the other hand, it was uncertain whether low muscle mass was associated with hospitalization (two studies in dialysis patients; RR:1.81; 95% CI:0.78 to 4.22; I2:59%). Further, limited ESKD progression measures prevented meta-analysis for this outcome. CONCLUSIONS: Low muscle strength, low muscle mass, and low physical performance were associated with higher mortality in CKD patients. In dialysis patients, diagnosed sarcopenia also represented higher mortality risk. Evidence to conclude associations with hospitalization and ESKD progression is currently lacking. PROSPERO REGISTRATION: CRD42020192198.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

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.

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.

Physical Activity and Health in Chronic Kidney Disease.

Clinical Background and Epidemiology: Low physical activity is a common phenotype in individuals living with chronic kidney disease (CKD). It increases as renal function declines and is associated with adverse clinical outcomes and a poor quality of life (QOL). Both behavioral and disease-related factors contribute to the low physical activity levels in CKD. CKD has profound negative effects on skeletal muscle structure and function that are related to impairments in mitochondrial function, inflammation, oxidative stress, metabolic acidosis, and other uremia-related factors. These factors promote muscle protein catabolism and wasting, and impair strength, physical performance, and cardiorespiratory fitness. Moreover, the high burden of comorbid disease contributes to patient fatigue, fear of injury, and poor exercise self-efficacy. All of these factors reinforce patient's sedentary behavior, leading to a vicious cycle of disease and disability that further compromises their health and QOL. Data from both observational studies and exercise interventions indicate that increasing levels of physical activity may provide a range of benefits in CKD patients, including attenuating declines in renal function, and improving markers of physical function, cardiovascular disease risk, and QOL. Unfortunately, these results have not led to widespread implementation of exercise programs in CKD, and physical inactivity and poor physical function remain hallmarks of the disease worldwide. Challenges and Solutions: There are many frequently cited barriers to implementing exercise programs in CKD. These include: a lack of training and knowledge about physical activity/exercise prescriptions and interventions among health professionals; inadequate time to implement exercise programs due to other clinical responsibilities; a lack of specific funding and incentives to develop these programs; and a poor quality of the data demonstrating efficacy of exercise. Many CKD patients also are unmotivated to incorporate exercise into their daily lives due to time constraints, depression, and other comorbid diseases, and poor self-efficacy for exercise. Given these barriers, it is not surprising that physical activity/exercise programs have not become a component of standard of care for CKD patients. We discuss several potential solutions to address these barriers, including: (1) providing better education and training for healthcare professionals who provide exercise advise and counselling to individuals with CKD; (2) providing incentives to reimburse payers to develop and maintain exercise programs in CKD; and (3) providing more personalized approaches to exercise prescription and implementation of exercise programs that consider the unique circumstances of individual CKD patients. In summary, low physical activity levels in CKD patients result from a combination of many factors that adversely impact patient's health and QOL. Addressing this problem will require comprehensive intervention strategies that consider both the unique pathophysiology of CKD and the individual circumstances of those living with the disease.

Association between physical activity and mortality in end-stage kidney disease: a systematic review of observational studies.

BACKGROUND: End-stage Kidney Disease patients have a high mortality and hospitalization risk. The association of these outcomes with physical activity is described in the general population and in other chronic diseases. However, few studies examining this association have been completed in end-stage Kidney Disease patients, raising the need to systematically review the evidence on the association of physical activity with mortality and hospitalization in this population. METHODS: Electronic databases (EBSCO, Scopus and Web of Science) and hand search were performed until March 2020 for observational studies reporting the association of physical activity with mortality or hospitalization in adult end-stage Kidney Disease patients on renal replacement therapy (hemodialysis, peritoneal dialysis and kidney transplant). Methodological quality of the included studies was assessed using the Quality in Prognosis Studies tool. The review protocol was registered in PROSPERO (CRD42020155591). RESULTS: Eleven studies were included: six in hemodialysis, three in kidney transplant, and two in hemodialysis and peritoneal dialysis patients. Physical activity was self-reported, except in one study that used accelerometers. All-cause mortality was addressed in all studies and cardiovascular mortality in three studies. Nine studies reported a significant reduction in all-cause mortality with increased levels of physical activity. Evidence of a dose-response relationship was found. For cardiovascular mortality, a significant reduction was observed in two of the three studies. Only one study investigated the association of physical activity with hospitalization. CONCLUSIONS: Higher physical activity was associated with reduced mortality in end-stage Kidney Disease patients. Future studies using objective physical activity measures could strengthen these findings. The association of physical activity with hospitalization should be explored in future investigations.

Accelerated decline in quadriceps area and Timed Up and Go test performance are associated with hip fracture risk in older adults with impaired kidney function.

OBJECTIVE: This study aimed to examine whether an accelerated decline in quadriceps cross-sectional area (CSA), attenuation (a surrogate of quality), and strength, as well as lower limb muscular function, are associated with hip fractures in older adults with impaired kidney function. DESIGN: Prospective population-based study. SETTING: Community-dwelling old population in Reykjavik, Iceland. SUBJECTS: A total of 875 older adults (mean baseline age 76 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study with impaired kidney function. METHODS: Quadriceps CSA and density were determined using computed tomography (CT), knee extension strength was measured with an isometric dynamometer chair, and muscular function was assessed using the Timed Up and Go (TUG) test. All muscle-related measurements were assessed twice over a mean follow-up of 5.2 years. Data on hip fracture incidence was obtained from medical records during a maximum of 8.4 years of follow-up time. RESULTS: Fully adjusted cox-proportional hazard regression models showed that a faster decline in quadriceps CSA and TUG test performance were significantly associated with increased hip fracture risk (HR = 1.55, 95% CI = 1.02-2.36, and HR = 1.80, 95% CI = 1.19-2.72, respectively). A faster decrease in quadriceps density and isometric knee extension strength were not associated with fracture risk. CONCLUSIONS: Accelerated decline in CT-derived quadriceps CSA and muscular function, as measured by the TUG test's performance, are predictive of hip fracture risk in older adults with impaired kidney function. TUG test is a simple measure and easily included in routine medical examinations, compared to CT scans, which seems to be useful for identifying a subgroup of individuals with high risk of fracture.

Muscle-Bone Crosstalk in Chronic Kidney Disease: The Potential Modulatory Effects of Exercise.

Chronic kidney disease (CKD) is a prevalent worldwide public burden that increasingly compromises overall health as the disease progresses. Two of the most negatively affected tissues are bone and skeletal muscle, with CKD negatively impacting their structure, function and activity, impairing the quality of life of these patients and contributing to morbidity and mortality. Whereas skeletal health in this population has conventionally been associated with bone and mineral disorders, sarcopenia has been observed to impact skeletal muscle health in CKD. Indeed, bone and muscle tissues are linked anatomically and physiologically, and together regulate functional and metabolic mechanisms. With the initial crosstalk between the skeleton and muscle proposed to explain bone formation through muscle contraction, it is now understood that this communication occurs through the interaction of myokines and osteokines, with the skeletal muscle secretome playing a pivotal role in the regulation of bone activity. Regular exercise has been reported to be beneficial to overall health. Also, the positive regulatory effect that exercise has been proposed to have on bone and muscle anatomical, functional, and metabolic activity has led to the proposal of regular physical exercise as a therapeutic strategy for muscle and bone-related disorders. The detection of bone- and muscle-derived cytokine secretion following physical exercise has strengthened the idea of a cross communication between these organs. Hence, this review presents an overview of the impact of CKD in bone and skeletal muscle, and narrates how these tissues intrinsically communicate with each other, with focus on the potential effect of exercise in the modulation of this intercommunication.

Intradialytic isometric handgrip exercise does not cause hemodynamic instability: A randomized, cross-over, pilot study.

Hemodialysis (HD) patients experience hemodynamic instability and intradialytic exercise seems to attenuate it. This study aimed to verify the acute hemodynamic response to different intradialytic handgrip exercise intensities in HD patients. In a randomized, cross-over, experimental pilot study, eight patients completed two experimental sessions and one control in random order: (a) regular HD; (b) low-intensity isometric handgrip exercise; and (c) moderate-intensity isometric handgrip exercise. BP and heart rate variability were recorded immediately before and every 15 minutes. Isometric handgrip exercise protocols, regardless of the intensity, did not lead to significant changes in hemodynamic stability, nor when compared to the control condition (P > .05). The systolic BP and double product significantly increased immediately after the moderate-intensity protocol (122.0 ± 15.9 vs 131.3 ± 19.8, P < .05; 9094.7 ± 1705.7 vs 9783.0 ± 1947.9, P < .05, respectively) but returned to the pre-exercise values 10 minutes later. We conclude that intradialytic isometric handgrip exercise does not induce hemodynamic instability at low and moderate intensities.