Publications by authors named "Kenneth R Wilund"

85 Publications

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

J Ren Nutr 2021 Aug 12. Epub 2021 Aug 12.

Alberta Kidney Care - South, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1053/j.jrn.2021.06.007DOI Listing
August 2021

Physical Activity and Health in Chronic Kidney Disease.

Contrib Nephrol 2021 Aug 3;199:1-13. Epub 2021 Aug 3.

Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.

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.
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http://dx.doi.org/10.1159/000517696DOI Listing
August 2021

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

BMC Nephrol 2021 Jun 18;22(1):227. Epub 2021 Jun 18.

Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University Institute of Maia, ISMAI, Maia, Portugal.

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.
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http://dx.doi.org/10.1186/s12882-021-02407-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212466PMC
June 2021

Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.

J Ren Nutr 2021 Sep 11;31(5):512-522. Epub 2021 Jun 11.

Division of Nutritional Sciences, University of Illinois, Urbana, Illinois; Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois. Electronic address:

Objective: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.

Design And Methods: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.

Results: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate.

Conclusions: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.
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http://dx.doi.org/10.1053/j.jrn.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403151PMC
September 2021

Anabolic Resistance of Muscle Protein Turnover Comes in Various Shapes and Sizes.

Front Nutr 2021 5;8:615849. Epub 2021 May 5.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population.
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http://dx.doi.org/10.3389/fnut.2021.615849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131552PMC
May 2021

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China.

J Ren Nutr 2021 Apr 19. Epub 2021 Apr 19.

Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK; School of Sport, Exercise & Health Sciences, Loughborough University, United Kingdom.

Objective: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China.

Methods: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake.

Results: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range).

Conclusion: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.
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http://dx.doi.org/10.1053/j.jrn.2021.03.003DOI Listing
April 2021

COVID-19 quarantine in chronic kidney disease patients: A focus on sarcopenia traits.

J Bras Nefrol 2021 Apr-Jun;43(2):293-294

Universidade de Brasília, Faculdade de Educação Física, Brasília, DF, Brasil.

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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257277PMC
July 2021

An International Delphi Survey on Exercise Priorities in CKD.

Kidney Int Rep 2021 Mar 18;6(3):657-668. Epub 2020 Dec 18.

Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada.

Introduction: Defining the role of exercise in chronic kidney disease (CKD) is a top research priority for people with CKD. We aimed to achieve consensus on specific research priorities in exercise and CKD among an international panel of stakeholders.

Methods: Using the Delphi method, patients/caregivers, researchers, clinicians, and policymakers submitted their top research priorities in round 1 and ranked their importance in rounds 2 and 3 using a 9-point Likert scale. The mean, median, and proportion of scores ranked 7 to 9 were calculated. Consensus was defined as priorities that scored above the overall mean and median score within each stakeholder panel. Qualitative description was used to understand participants' rankings.

Results: Seventy participants (78% response) completed round 1: 15 (21.4%) clinicians, 33 (47.1%) researchers, 13 (18.6%) policymakers, and 9 (12.9%) patients; (85.7%) completed round 3. The top research priorities were defining exercise-related outcomes meaningful to patients, identifying patients' motivation and perspective towards exercise, understanding the effect of exercise on the risk of institutionalization, mortality, and mobility, and understanding the effect of pre- and post-transplant exercise on postoperative recovery. Themes from the qualitative analysis were individualization, personal experience, and holistic approach to exercise (patients), the need to address common clinical problems (clinicians), developing targeted interventions (researchers), and the importance of evidence-based development versus implementation (policymakers).

Conclusions: Preventing physical disability was a common priority. Policymakers emphasized that more efficacy studies were needed. Other panels expressed the need for holistic and targeted exercise interventions and for outcomes that address common clinical problems.
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http://dx.doi.org/10.1016/j.ekir.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938076PMC
March 2021

Working on Wellness: Impact of a Pilot Workplace Wellness Program in a Hemodialysis Center.

Nephrol Nurs J 2021 Jan-Feb;48(1):49-55

Professor, the Department of Kinesiology and Community Health, the University of Illinois at Urbana-Champaign, Champaign, IL.

This article describes the impact of a 12-week workplace wellness program on staff (n = 14) of an outpatient hemodialysis center. The program focused on decreasing dietary sodium and increasing habitual physical activity. The average systolic and diastolic blood pressure of participants decreased by 16.9±21.6 mmHg (p < 0.05) and 4.1±14.0 mmHg (p < 0.05), and body weight decreased by 2.7±1.9kg (p < 0.05). The mean step count at baseline was 7,052±3,278 but increased to 10,388±2,882 (p < 0.05) during a walking challenge. There was a reduction in self-reported barriers to making healthy nutritional changes (p < 0.05) and engaging in habitual physical activity (p < 0.05). Our pilot findings suggest that workplace wellness programs in hemodialysis centers are feasible and effective.
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March 2021

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

Calcif Tissue Int 2021 04 2;108(4):461-475. Epub 2021 Jan 2.

Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University Institute of Maia, ISMAI, Maia, Portugal.

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.
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http://dx.doi.org/10.1007/s00223-020-00782-4DOI Listing
April 2021

Cardiovascular Autonomic Dysfunction and Falls in People With Multiple Sclerosis: Is There a Link? An Opinion Article.

Front Neurosci 2020 7;14:610917. Epub 2020 Dec 7.

Motor Control Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

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http://dx.doi.org/10.3389/fnins.2020.610917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750464PMC
December 2020

Depressive Disorders Are Associated With Risk of Falls in People With Chronic Kidney Disease.

J Am Psychiatr Nurses Assoc 2020 Nov 5:1078390320970648. Epub 2020 Nov 5.

Jacob Sosnoff, PhD, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Objectives: People with chronic kidney disease (CKD) are at increased risk for falls and fall-related injuries. Depressive disorders (DEP) are common in individuals with CKD and may increase the risk of falls and fall-related injuries. However, not much is known about the relationship between DEP and falls in people with CKD. The purpose of this study was to determine the influence of DEP on the relationship between CKD, falls, and fall-related injuries.

Method: Using the Behavioral Risk Factor Surveillance System, we identified 16,574 adults with CKD. Patients with CKD were stratified by history of self-reported DEP (SRDEP), and multivariate logistic regression was conducted to determine the odds for falls and fall-related injuries among those with and without SRDEP.

Results: In unadjusted regression analysis, falls (OR = 2.40, 95% CI = 2.08-2.76) and fall-related injuries (OR = 2.12, 95% CI = 1.72-2.59) were higher in individuals with CKD and history of SRDEP compared to those with CKD and no history of SRDEP. Adjustment for confounders had little effect on the relationship between a history of SRDEP and either falls (AOR = 1.87, 95% CI = 1.60-2.19) or fall-related injuries (AOR = 1.58, 95% CI = 1.26-1.97).

Conclusions: People with CKD and DEP are at increased odds for falls and fall-related injuries even after adjustment for sociodemographic, lifestyle factors, and comorbidities. Prospective studies are warranted to further understand this relationship, but it may be prudent for clinicians, in particular nurses, to consider fall risk when treating DEP in patients with CKD.
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http://dx.doi.org/10.1177/1078390320970648DOI Listing
November 2020

Pilot study to reduce interdialytic weight gain by provision of low-sodium, home-delivered meals in hemodialysis patients.

Hemodial Int 2021 Apr 4;25(2):265-274. Epub 2020 Nov 4.

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Introduction: Patients with kidney failure undergoing maintenance hemodialysis (HD) therapy are routinely counseled to reduce dietary sodium intake to ameliorate sodium retention, volume overload, and hypertension. However, low-sodium diet trials in HD are sparse and indicate that dietary education and behavioral counseling are ineffective in reducing sodium intake. This study aimed to determine whether 4 weeks of low-sodium, home-delivered meals in HD patients reduces interdialytic weight gain (IDWG). Secondary outcomes included changes in dietary sodium intake, thirst, xerostomia, blood pressure, volume overload, and muscle sodium concentration.

Methods: Twenty HD patients (55 ± 12 years, body mass index [BMI] 40.7 ± 16.6 kg/m ) were enrolled in this study. Participants followed a usual (control) diet for the first 4 weeks followed by 4 weeks of three low-sodium, home-delivered meals per day. We measured IDWG, hydration status (bioimpedance), standardized blood pressure (BP), food intake (3-day dietary recall), and muscle sodium (magnetic resonance imaging) at baseline (0 M), after the 4-week period of usual diet (1 M), and after the meal intervention (2 M).

Findings: The low-sodium meal intervention significantly reduced IDWG when compared to the control period (-0.82 ± 0.14 kg; 95% confidence interval, -0.55 to -1.08 kg; P < 0.001). There were also 1 month (1 M) to 2 month (2 M) reductions in dietary sodium intake (-1687 ± 297 mg; P < 0.001); thirst score (-4.4 ± 1.3; P = 0.003), xerostomia score (-6.7 ± 1.9; P = 0.002), SBP (-18.0 ± 3.6 mmHg; P < 0.001), DBP (-5.9 ± 2.0 mmHg; P = 0.008), and plasma phosphorus -1.55 ± 0.21 mg/dL; P = 0.005), as well as a 0 M to 2 M reduction in absolute volume overload (-1.08 ± 0.33 L; P = 0.025). However, there were no significant changes in serum or tissue sodium (all P > 0.05).

Discussion: Low-sodium, home-meal delivery appears to be an effective method for improving volume control and blood pressure in HD patients. Future studies with larger sample sizes are needed to examine the long-term effects of home-delivered meals on these outcomes and to assess cost-effectiveness.
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http://dx.doi.org/10.1111/hdi.12902DOI Listing
April 2021

Integrin-associated ILK and PINCH1 protein content are reduced in skeletal muscle of maintenance haemodialysis patients.

J Physiol 2020 12 2;598(24):5701-5716. Epub 2020 Nov 2.

Department of Life Sciences, Sport and Exercise Science Research Center, University of Roehampton, London, UK.

Key Points: Patients with renal failure undergoing maintenance haemodialysis are associated with insulin resistance and protein metabolism dysfunction. Novel research suggests that disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in haemodialysis. ILK, PINCH1 and pFAK were significantly decreased in haemodialysis compared to controls, whereas Rac1 and Akt2 showed no different between groups. Rac1 deletion in the Rac1 knockout model did not alter the expression of integrin-associated proteins. Phenylalanine kinetics were reduced in the haemodialysis group at 30 and 60 min post meal ingestion compared to controls; both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in haemodialysis patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients.

Abstract: Muscle atrophy, insulin resistance and reduced muscle phosphoinositide 3-kinase-Akt signalling are common characteristics of patients undergoing maintenance haemodialysis (MHD). Disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in MHD patients. Eight MHD patients (age: 56 ± 5 years: body mass index: 32 ± 2 kg m ) and non-diseased controls (age: 50 ± 2 years: body mass index: 31 ± 1 kg m ) received primed continuous l-[ring- H ]phenylalanine before consuming a mixed meal. Phenylalanine metabolism was determined using two-compartment modelling. Muscle biopsies were collected prior to the meal and at 300 min postprandially. In a separate experiment, skeletal muscle tissue from muscle-specific Rac1 knockout (Rac1 mKO) was harvested to investigate whether Rac1 depletion disrupted the cytoskeleton-integrin linkage, allowing for cross-model examination of proteins of interest. ILK, PINCH1 and pFAK were significantly lower in MHD (P < 0.01). Rac1 and Akt showed no difference between groups for the human trial. Rac1 deletion in the Rac1 mKO model did not alter the expression of integrin-associated proteins. Phenylalanine rates of appearance and disappearance, as well as metabolic clearance rates, were lower in the MHD group at 30 and 60 min post meal ingestion compared to controls (P < 0.05). Both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin-cytoskeleton linkage are reduced in MHD patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients.
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http://dx.doi.org/10.1113/JP280441DOI Listing
December 2020

Pilot feasibility study examining the effects of a comprehensive volume reduction protocol on hydration status and blood pressure in hemodialysis patients.

Hemodial Int 2020 07 12;24(3):414-422. Epub 2020 May 12.

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.

Introduction: Chronic volume overload is a persistent problem in hemodialysis (HD) patients. The purpose of this study was to investigate the impacts of comprehensive volume reduction protocol on HD patient's hydration status and blood pressure (BP).

Methods: Twenty-three HD patients (age = 55.7 ± 13.3 years) completed a 6-month comprehensive volume control protocol consisting of: reducing postdialysis weight; reducing BP medication prescriptions; and weekly intradialytic counseling to reduce dietary sodium intake and interdialytic weight gain (IDWG). The primary outcome was volume overload (VO) measured by bioelectrical impedance spectroscopy. Secondary outcomes included: IDWG, postdialysis weight, estimated dry weight (EDW), dietary sodium intake, BP and BP medication prescriptions.

Findings: From baseline (0M) to 6 months (6M), significant improvements were noted in: VO (0M 3.9 ± 3.9 L vs. 6M 2.6 ± 3.4 L, P = 0.003), postdialysis weight (0M 89.4 ± 23.1 kg vs. 6M 87.6 ± 22.2 kg; P = 0.012), and EDW (0M 89.0 ± 23.2 vs. 6M 86.7 ± 22.5 kg., P = 0.009). There was also a trend for a reduction in monthly averaged IDWG (P = 0.053), and sodium intake (0M 2.9 ± 1.6 vs. 6M 2.3 ± 1.1 g/d, P = 0.125). Neither systolic BP (0M 162 ± 27 vs. 6M 157 ± 23 mmHg, P = 0.405) nor diastolic BP (0M 82 ± 21 vs. 6M 82 ± 19 mmHg, P = 0.960) changed, though there was a significant reduction in the total number of BP medications prescribed (0M 3.0 ± 1.0 vs. 6M 1.5 ± 1.0 BP meds; P = 0.004).

Discussion: Our volume reduction protocol significantly improved HD patient's hydration status. While BP did not change, the reduction in prescribed BP medication number suggests improved BP control. Despite these overall positive findings, the magnitude of change in most variables was modest. Comprehensive changes in HD clinics may be necessary to realize more clinically significant results.
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http://dx.doi.org/10.1111/hdi.12841DOI Listing
July 2020

Reply to Comments: Comparison of Methods Study between a Photonic Crystal Biosensor and Certified ELISA to Measure Biomarkers of Iron Deficiency in Chronic Kidney Disease Patients.

Sensors (Basel) 2020 Feb 19;20(4). Epub 2020 Feb 19.

Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

In this brief note, we respond to the comments made by Dr [...].
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http://dx.doi.org/10.3390/s20041149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070363PMC
February 2020

A Comparison of Intradialytic versus Out-of-Clinic Exercise Training Programs for Hemodialysis Patients.

Blood Purif 2020 18;49(1-2):151-157. Epub 2019 Dec 18.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA,

Background: Physical inactivity is prevalent and linked with a variety of unfavorable clinical outcomes in hemodialysis patients. To increase physical activity (PA) and improve quality of life in this population, intradialytic and out-of-clinic exercise interventions have been implemented in many studies. However, there is still a lack of consensus in the literature on which type of exercise intervention is more feasible and effective.

Summary: This review provides a brief overview of intradialytic and out-of-clinic exercise protocols utilized in previous studies. We also examine data related to the feasibility of each approach, and their efficacy for improving cardiovascular health, muscle mass, strength, and physical function. Key Messages: The benefits from most intradialytic and out-of-center exercise training interventions published to date have been modest or inconsistent. Furthermore, neither appears to provide a significant advantage over the other in terms of benefits for cardiovascular health, muscle mass, strength, and physical function. A significant concern is that most intradialytic and out-of-center exercise interventions are mandated exercise prescriptions that include either endurance or resistance training exercises, performed at low-moderate intensities, for a total of 60-135 min of exercise/week. This volume, intensity, and variety of exercise are far less than what is recommended in most PA guidelines. This type of structured activity is also boring for most patients. To enhance the effectiveness of exercise interventions, we suggest using the intradialytic period to provide patients guidance on how they can best incorporate more activity into their lives, based on their individual needs and barriers.
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http://dx.doi.org/10.1159/000503772DOI Listing
December 2020

Gut Microbiota and Cardiometabolic Risk Factors in Hemodialysis Patients: A Pilot Study.

Top Clin Nutr 2019 Apr-Jun;34(2):153-160

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign.

The gut microbiota has been implicated in the pathogenesis and progression of kidney disease. However, little is known about the gut microbiota in hemodialysis (HD) patients. We assessed the gut microbiota and its relationship with clinical variables in ten HD patients. We found that the -to- ratio was positively associated with traditional risk factors for cardiovascular disease. Furthermore, was positively associated with carbohydrate intake and negatively associated with arterial stiffness. Finally, endotoxemia was inversely associated with butyrate producers. Future studies should assess if targeting the gut microbiota result in a lower burden for cardiovascular disease in HD patients.
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http://dx.doi.org/10.1097/TIN.0000000000000170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880937PMC
November 2019

Managing Hyperkalemia: Another Benefit of Exercise in People With Chronic Kidney Disease?

J Ren Nutr 2020 09 22;30(5):380-383. Epub 2019 Nov 22.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois.

People with chronic kidney disease (CKD) are at increased risk of hyperkalemia, an electrolyte abnormality that can cause serious, sometimes fatal, cardiac arrhythmias. Muscle contraction causes potassium to be released from cells, increasing serum potassium concentrations. However, these effects are transient, and the long-term impact of exercise training on hyperkalemia risk in CKD patients is largely unknown. In this review, we examine the effects of exercise on factors affecting potassium balance in people with CKD, highlighting the potential benefits of regular exercise on hyperkalemia risk in this population. Although regular exercise is already recommended for people with CKD, research examining this hypothesis may lead to novel therapeutic treatments for this life-threatening condition.
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http://dx.doi.org/10.1053/j.jrn.2019.10.001DOI Listing
September 2020

Effect of Oral Nutritional Supplementation With and Without Exercise on Nutritional Status and Physical Function of Adult Hemodialysis Patients: A Parallel Controlled Clinical Trial (AVANTE-HEMO Study).

J Ren Nutr 2020 03 10;30(2):126-136. Epub 2019 Oct 10.

Departamento de Nefrología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico. Electronic address:

Objective: Protein energy wasting affects the nutritional status (NS) and physical function (PF) of dialysis patients. Among the different anabolic strategies to improve NS and PF, oral nutritional supplementation (ONS) and resistance exercise (RE) or aerobic exercise (AE) have been shown to be effective. Nevertheless, the combination of both anabolic strategies has not been completely evaluated. The aim of this study is to assess the effect of exercise combined with ONS versus ONS without exercise during hemodialysis sessions on PF and NS indicators.

Methods: Young hemodialysis patients (29 ± 9.3 years) with predominantly unknown causes of renal disease (80%) were divided into the following 3 groups during a period of 12 weeks: (1) ONS (n = 15), (2) ONS + RE (n = 15), and (3) ONS + AE (n = 15). Anthropometric, biochemical, PF, and quality of life measurements were recorded at baseline and after 3 months. Repeated measures analysis of variance and effect sizes (Cohen's d) were used to assess the effect of exercise and nutrition (ISRCTN registry 10251828).

Results: At the completion of the study, the ONS and ONS + RE groups exhibited statistically significant increases in body weight, body mass index, and in the percentage of fat mass (P < .05); the greatest effect sizes were observed in the ONS + RE group (d = 0.30 for body weight, d = 0.63 for body mass index, and d = 0.90 for the percentage of fat mass). Groups with RE and AE had statistically significant increases and large effect sizes in the six-minute walk test (RE: d = 0.94, P = .02; AE: d = 1.11, P = .03), sit-to-stand test (RE: d = 0.81, P = .041; AE: d = 1.20, P = .002), timed up and go test (RE: d = 1.04, P = .036; AE: d = 1.6, P = .000), and muscle strength (RE: d = 1.01, P = .000; AE: d = 0.60, P = .003). Regarding quality of life, the ONS + RE group had more areas of improvement at the end of the study, followed by the ONS + AE group. No statistically significant differences were found in the repeated measures ANOVA.

Conclusions: The combination of exercise with ONS had larger effects on PF than on ONS alone. Further studies to examine the impact of exercise on the effect of oral nutritional supplementation in dialysis patients are indicated.
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http://dx.doi.org/10.1053/j.jrn.2019.06.010DOI Listing
March 2020

A Critical Review of Exercise Training in Hemodialysis Patients: Personalized Activity Prescriptions Are Needed.

Exerc Sport Sci Rev 2020 01;48(1):28-39

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL.

Exercise training appears to have modest or inconsistent benefits in hemodialysis patients. This may be due to the low volume and intensity of exercise often prescribed. To address this, research is needed to evaluate the efficacy of individualized exercise prescriptions as a component of a comprehensive lifestyle intervention strategy that gives patients more autonomy to choose preferred types of physical activity.
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http://dx.doi.org/10.1249/JES.0000000000000209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910960PMC
January 2020

The association of positive affect and cardiovascular health in Hispanics/Latinos with chronic kidney disease: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Prev Med Rep 2019 Sep 7;15:100916. Epub 2019 Jun 7.

Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States of America.

The beneficial influence of positive affect (e.g., joy) remains unexplored in relation to heart health in adults with chronic kidney disease (CKD)-a population at increased risk for poor cardiovascular health (CVH). Therefore, we evaluated the association of positive affect and CVH in a diverse U.S. population of Hispanics/Latinos with CKD. We analyzed cross-sectional data of adults ages 18-74 enrolled between 2008 and 2011 in the Hispanic Community Health Study/Study of Latinos with prevalent CKD (N = 1712). Positively worded items from the Center for Epidemiologic Studies Depression Scale were used to create a composite positive affect score (0-6; higher scores indicate greater positive affect). Prevalent CKD was defined as estimated glomerular filtration <60 ml/min/1.73 m or urine albumin-to-creatinine ratio ≥30 mg/g. A composite CVH score was calculated using diet, body mass index, physical activity, cholesterol, blood pressure, fasting glucose, and smoking status. Each metric was defined as ideal, intermediate, or poor to compute an additive score. Linear regression was used for continuous scores of CVH and logistic regression for binary treatment (e.g., ≥4 Ideal). In participants with CKD, each unit increase in the positive affect score was associated with higher CVH scores when modeling CVH as a continuous outcome (β = 0.06, 95% CI = 0.01, 0.11). Similarly, a 1-unit increase in positive affect was associated with 1.15 times the odds of having >4 (vs. <4) ideal CVH indicators. Positive affect is associated with favorable CVH profiles in Hispanics/Latinos with CKD. Replication and prospective studies are needed to elucidate whether emotional well-being is a potential therapeutic target for intervention.
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http://dx.doi.org/10.1016/j.pmedr.2019.100916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595078PMC
September 2019

Results from the randomized controlled IHOPE trial suggest no effects of oral protein supplementation and exercise training on physical function in hemodialysis patients.

Kidney Int 2019 09 2;96(3):777-786. Epub 2019 Apr 2.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. Electronic address:

Few long-term studies have assessed whether changes in both diet and exercise can improve the health and quality of life (QOL) of hemodialysis (HD) patients. Here we examined whether 12 months of intradialytic protein supplementation and endurance exercise improves physical function, risk of cardiovascular disease (CVD), and QOL in HD patients in a randomized controlled trial (RCT). A total of 138 HD patients (average age 58 years) were assigned for 12 months to control, intradialytic protein, or protein plus exercise groups. The protein and protein plus exercise groups consumed an oral protein supplement (30 grams of whey) three days/week during dialysis. The protein plus exercise group cycled for 30-45 minutes during dialysis treatment. The primary outcome was change in physical function at 12 months, assessed by a shuttle walk test. Secondary outcomes included arterial stiffness, blood pressure, body composition, muscle strength, markers of nutritional status, and QOL. Assessments were conducted at baseline, 6 and 12 months. In total, 101 patients completed the intervention. There were no significant differences between groups in shuttle walk test performance from baseline to 12 months. There were trends for improvements in some secondary measures of physical function and strength in the protein and protein plus exercise groups at six or 12 months, but these did not reach statistical significance. Thus, our trial did not demonstrate significant improvements in markers of physical function, risk of CVD or QOL after one year of intradialytic oral OPS and aerobic exercise training. More comprehensive lifestyle management may be needed to uncover robust improvements in the health and QOL of HD patients.
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http://dx.doi.org/10.1016/j.kint.2019.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708720PMC
September 2019

Epidemiology of falls and fall-related injuries among middle-aged adults with kidney disease.

Int Urol Nephrol 2019 Sep 4;51(9):1613-1621. Epub 2019 Jun 4.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.

Purpose: Comorbidities, such as kidney disease (CKD), increase the likelihood of falls and fall-related injuries. Despite the focus of most research in this population on older adults, falls are a significant cause of injury throughout adulthood. Therefore, we aimed to describe the epidemiology of falls in middle-aged adults with kidney diseases.

Methods: We analyzed falls and fall-related injuries among middle-aged adults (45-65 years old) with and without CKD included in the 2014 Behavioral Risk Factor Surveillance System (BRFSS) utilizing multivariate logistic regression and complex sample survey data analysis procedures.

Results: Middle-aged adults with CKD were more likely to suffer a fall (2.30, 95% CI 2.07-2.55) and a fall-related injury (1.54, 95% CI 1.32-1.80) compared to those without CKD. However, only the increased likelihood for falls remained significant after correction for multiple demographic, health, lifestyle, and comorbid conditions (AOR 1.22, 95% CI 1.08-1.39). Among adults with CKD, general health status, smoking, and total comorbidity scores were significant predictors of falls and fall-related injuries (p < 0.05 for all). Furthermore, individual comorbidities such as COPD, asthma, depressive disorders, stroke, and arthritis also predicted falls and fall-related injuries (p < 0.05 for all).

Conclusion: Middle-aged adults with CKD were more likely than those without CKD to fall and suffer a fall-related injury. However, injury risk did not remain elevated after accounting for differences between groups. The presence of comorbidities, especially depressive disorders, was associated with increased odds for falls and fall-related injuries. Given the high prevalence of depression among adults with CKD, the relationship between depression and falls warrants further examination.
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http://dx.doi.org/10.1007/s11255-019-02148-8DOI Listing
September 2019

Sustained exercise programs for hemodialysis patients: The characteristics of successful approaches in Portugal, Canada, Mexico, and Germany.

Semin Dial 2019 07 13;32(4):320-330. Epub 2019 May 13.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois.

Despite having good intentions, hemodialysis (HD) clinics often fail to sustain exercise programs that they initiate. There are many reasons for this, including a lack of funding, inadequate training of the clinic staff, a lack of exercise professionals to manage the program or train the staff, and the many challenges inherent to exercising a patient population with multiple comorbid diseases. Despite these barriers, there are several outstanding examples of successful exercise programs in HD clinics throughout the world. The aim of this manuscript is to review the characteristics of four successfully sustained HD exercise programs in Portugal, Canada, Mexico, and Germany. We describe the unique approaches they have used to fund and manage their programs, the varied exercise prescriptions they incorporate, the unique challenges they face, and discuss the benefits they have seen. While the programs differ in many regards, a consistent theme is that they each have substantial and committed support from the entire clinic staff, including the nephrologists, administration, nurses, dietitians, and technicians. This suggests that exercise programs in HD clinics can be successfully implemented and sustained provided significant effort is made to foster a culture of physical activity throughout the clinic.
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http://dx.doi.org/10.1111/sdi.12814DOI Listing
July 2019

Addressing myths about exercise in hemodialysis patients.

Semin Dial 2019 07 25;32(4):297-302. Epub 2019 Apr 25.

Department of Therapies and Renal Medicine, King's College Hospital NHS Trust, London, UK.

Despite decades of research, there are few published guidelines related to the safety and efficacy of exercise training in hemodialysis patients. This has led to disparate recommendations regarding the type, intensity, and timing for exercise, especially for patients with multiple comorbidities. Many common recommendations are not supported by research data, so their justification is uncertain. These recommendations include exercising in the first hour of dialysis; not exercising if hypertensive, cramping, or volume overloaded; avoiding heavy weights on vascular access limb; clinicians managing an exercise program; intradialytic exercise or interdialytic exercise is better; and strength training during dialysis is impractical. The purpose of this review is to describe the evidence that supports or refutes these beliefs. In summary, these beliefs or myths have generally led to an overly conservative approach to exercise that serves as a barrier to increasing physical activity levels in an overly sedentary population that could benefit from moving more.
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http://dx.doi.org/10.1111/sdi.12815DOI Listing
July 2019

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

Kidney Int Rep 2018 Nov 17;3(6):1403-1415. Epub 2018 Aug 17.

Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Introduction: Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy.

Methods: Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m) received primed continuous L-[-H]phenylalanine and L-[1-C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-H]leucine-labeled eggs.

Results: Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%;  = 0.03). Basal muscle caspase-3 protein content was elevated ( = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced ( 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) ( = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; 0.004).

Conclusions: MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.
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http://dx.doi.org/10.1016/j.ekir.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224635PMC
November 2018

Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions.

Atherosclerosis 2018 10 26;277:1-6. Epub 2018 Jul 26.

Department of Exercise Science, University of South Carolina, Columbia, SC, USA. Electronic address:

Background And Aims: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions.

Methods: Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions.

Results: Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10) reduced plasma GlycA (-8.26 ± 1.8 μmol/L). This reduction remained significant (-9.12 ± 1.9 μmol/L, p = 1.22 × 10) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21-0.38, p < 0.0001).

Conclusions: Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298739PMC
October 2018

Effects of acute intradialytic exercise on cardiovascular responses in hemodialysis patients.

Hemodial Int 2018 10 9;22(4):524-533. Epub 2018 May 9.

Department of Kinesiology and Community Health, Urbana, Illinois, USA.

Background: In patients with kidney failure requiring hemodialysis (HD) treatment, intradialytic exercise (IDEX) has been advocated for its feasibility and effectiveness in improving important health outcomes. However, IDEX as an adjunct therapeutic strategy is infrequently implemented, in part due to potential risks of IDEX, especially in patients with chronic volume overload. This study was performed to evaluate the safety of IDEX performed at different time points by examining its effect on intradialytic cardiovascular hemodynamics.

Methods: In a randomized cross-over study (n = 12), intradialytic changes in brachial, aortic, and cardiac hemodynamics and autonomic function were examined during a HD session; (1) without exercise; (2) with 30 min of IDEX performed in the first hour of treatment; or (3) with 30 min of IDEX in the third hour of treatment.

Results: IDEX during either the first or third hour did not exacerbate hemodynamic instability during treatment regardless of patient's hydrations status. While there were transient increases in stroke volume, cardiac output, and heart rate during IDEX, intradialytic changes in brachial and aortic blood pressure, cardiac hemodynamics, and autonomic function were similar on days with and without IDEX.

Conclusion: These results indicate that IDEX does not exacerbate hemodynamic instability during HD, regardless of a patient's hydration status or the timing of exercise.
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http://dx.doi.org/10.1111/hdi.12664DOI Listing
October 2018
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