Publications by authors named "Alice C Smith"

90 Publications

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

J Ren Nutr 2021 Jul 19. Epub 2021 Jul 19.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK; Leicester Biomedical Research Centre, Leicester, UK.

In chronic kidney disease (CKD), handgrip strength (HGS) is recommended as a surrogate measure of protein-energy status and functional status. However, it is not routinely used because of inconsistencies such as the optimal timing of the HGS measurement and unclear guidance regarding technique. We aimed to determine the extent of variation in the protocols and methods of HGS assessment. We aimed to identify clinical and epidemiological studies conducted on CKD that reported on the use of HGS as an outcome. A systematic literature search identified n = 129 studies with a total participant population of n = 35,192. We identified large variations in all aspects of the methodology including body and arm position, repetitions, rest time, timing, familiarization, and how scores were calculated. The heterogeneous methodologies used reinforce the need to standardize HGS measurement. After reviewing previously employed methodology in the literature, we propose a comprehensive HGS assessment protocol for use in CKD.
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http://dx.doi.org/10.1053/j.jrn.2021.06.005DOI Listing
July 2021

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

Nephrology (Carlton) 2021 Jul 3. Epub 2021 Jul 3.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Introduction: Chronic kidney disease (CKD) is characterized by adverse physical function. Mechanical muscle power describes the product of muscular force and velocity of contraction. In CKD, the role of mechanical muscle power is poorly understood and often overlooked as a target in rehabilitation. The aims of this study were to investigate the association of mechanical power with the ability to complete activities of daily living and physical performance.

Method: Mechanical muscle power was estimated using the sit-to-stand-5 test. Legs lean mass was derived using bioelectrical impedance analysis. Physical performance was assessed using gait speed and 'timed-up-and-go' (TUAG) tests. Self-reported activities of daily living (ADLs) were assessed via the Duke Activity Status Index. Balance and postural stability (postural sway and velocity) was assessed using a FysioMeter. Sex-specific tertiles were used to determine low levels of power.

Results: One hundred and two non-dialysis CKD participants were included (age: 62.0 (±14.1) years, n = 49 males (48%), eGFR: 38.0 (±21.5) ml/min/1.73m ). The mean relative power was 3.1 (±1.5) W/kg in females and 3.3 (±1.3) W/kg in males. Low relative power was found in 34% of patients. Relative power was an independent predictor of ADLs (β = .413, p = .004), and TUAG (β = -.719, p < .001) and gait speed (β = .404, p = .003) performance. Skeletal muscle mass was not associated with any outcomes.

Conclusion: Knowledge of the factors that mediate physical function impairment is crucial for developing effective interventions. Incorporation of power-based training focusing primarily on movement velocity may present the best strategy for improving physical function in CKD, above those that focus on increasing muscle mass.
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http://dx.doi.org/10.1111/nep.13920DOI Listing
July 2021

Seven months of aerobic intradialytic exercise training can prevent muscle loss in haemodialysis patients: an ultrasonography study.

Int Urol Nephrol 2021 Jun 28. Epub 2021 Jun 28.

Department of Physical Education and Sport Science, University of Thessaly, 42100, Trikala, Greece.

Purpose: This study aimed to evaluate the effects of 7-month intradialytic exercise training (IDE) on vastus lateralis (VL) muscle architecture, functional capacity and quality of life in stable haemodialysis (HD) patients.

Methods: 44 HD patients were randomly assigned into an Exercise Group (EG = 21), which they received 7 months of IET, at 60% of pre-assessed maximum aerobic power, 3/week) or into a Control Group (CG = 23, no exercise). VL architecture was evaluated with ultrasonography, functional capacity was assessed using a series of functional tests (6 min walking test, 5 repetitions sit-to-stand, sit-to-stand 60 s, handgrip strength), and maximal aerobic power determined with a modified version of the Åstrand test. Quality of life and fatigue levels were evaluated using validated questionnaires.

Results: VL fascicle angle and length did not change significantly in both groups (P > 0.05). Muscle thickness decreased in CG (P = 0.02) while it was fully preserved in the EG. Functional capacity increased only in the EG (6 min walking test 15.79 ± 12.35%, P < 0.001; max aerobic power 26.36 ± 1.24%, P < 0.001; STS-60rep: 10.23 ± 1.60%, P < 0.000; hand grip strength: 5.14 ± 28.30%, P < 0.02).

Conclusion: Intradialytic aerobic exercise training, improves functional capacity and prevents thigh muscle mass loss in HD patients. It is evident that muscle ultrasonography could play a pivotal role in assessing muscle quality changes in haemodialysis patients. A higher level of training intensity or combination with resistance exercises may be required to further improve anabolism and influence muscle architecture in this patient population.

Clinical Trial Registry Number: NCT03905551.
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http://dx.doi.org/10.1007/s11255-021-02931-6DOI Listing
June 2021

A Cost-Effective Analysis of the CYCLE-HD Randomized Controlled Trial.

Kidney Int Rep 2021 Jun 8;6(6):1548-1557. Epub 2021 Apr 8.

Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

Introduction: No formal cost-effectiveness analysis has been performed for programs of cycling exercise during dialysis (intradialytic cycling [IDC]). The objective of this analysis is to determine the effect of a 6-month program of IDC on health care costs.

Methods: This is a retrospective formal cost-effectiveness analysis of adult participants with end-stage kidney disease undertaking in-center maintenance hemodialysis enrolled in the CYCLE-HD trial. Data on hospital utilization, primary care consultations, and prescribed medications were extracted from medical records for the 6 months before, during, and after a 6-month program of thrice-weekly IDC. The cost-effectiveness analysis was conducted from a health care service perspective and included the cost of implementing the IDC intervention. The base-case analyses included a 6-month "within trial" analysis and a 12-month "within and posttrial" analysis considering health care utilization and quality of life (QoL) outcomes.

Results: Data from the base-case within trial analysis, based on 109 participants ( = 56 control subjects and  = 53 IDC subjects) showed a reduction in health care utilization costs between groups, favoring the IDC group, and a 73% chance of IDC being cost-effective compared with control subjects at a willingness to pay of £20,000 and £30,000 per quality-adjusted life year (QALY) gained. When QoL data points were extrapolated forward to 12 months, the probability of IDC being cost-effective was 93% and 94% at £20,000 and £30,000 per QALY gained. Sensitivity analysis broadly confirms these findings.

Conclusion: A 6-month program of IDC is cost-effective and the implementation of these programs nationally should be a priority.
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http://dx.doi.org/10.1016/j.ekir.2021.02.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207470PMC
June 2021

Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT.

Health Technol Assess 2021 Jun;25(40):1-52

School of Health Sciences, Queen Margaret University, Edinburgh, UK.

Background: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown.

Objectives: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients.

Design: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis.

Setting: The setting was five dialysis units across the UK from 2015 to 2019.

Participants: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year.

Interventions: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training.

Main Outcome Measures: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted.

Results: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention,  = 127; control,  = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units;  = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention ( = 69) and control ( = 56) groups.

Limitations: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation.

Conclusions: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis.

Future Work: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness.

Trial Registration: Current Controlled Trials ISRCTN83508514.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 40. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta25400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256322PMC
June 2021

Reliability and Validity of the Patient Activation Measure in Kidney Disease: Results of Rasch Analysis.

Clin J Am Soc Nephrol 2021 Jun 11;16(6):880-888. Epub 2021 Jun 11.

Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Background And Objectives: Despite the increasing prioritization of the promotion of patient activation in nephrology, its applicability to people with CKD is not well established. Before the Patient Activation Measure is universally adopted for use in CKD, it is important to critically evaluate this measure. The aim of this study was to describe the psychometric properties of the Patient Activation Measure in CKD.

Design, Setting, Participants, & Measurements: A survey containing the 13-item Patient Activation Measure was completed by 942 patients with CKD, not treated with dialysis. Data quality was assessed by mean, item response, missing values, floor and ceiling effects, internal consistency (Cronbach's alpha and average interitem correlation), and item-rest correlations. Rasch modeling was used to assess item performance and scaling (item statistics, person and item reliability, rating scale diagnostics, factorial test of residuals, and differential item functioning).

Results: The item response was high, with a small number of missing values (<1%). Floor effect was small (range 1%-5%), but the ceiling effect was above 15% for nine items (range 15%-38%). The Patient Activation Measure demonstrated good internal consistency overall (Cronbach α=0.925, and average interitem correlation 0.502). The difficulty of the Patient Activation Measure items ranged from -0.90 to 0.86. Differential item functioning was found for disease type (item 3) and age (item 12). The person separation index was 9.48 and item separation index was 3.21.

Conclusions: The 13-item Patient Activation Measure appears to be a suitably reliable and valid instrument for assessing patient activation in CKD. In the absence of a kidney-specific instrument, our results support the 13-item Patient Activation Measure as a promising measure to assess activation in those with CKD, although consideration for several items is warranted. The high ceiling effect may be a problem when using the 13-item Patient Activation Measure to measure changes over time.
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http://dx.doi.org/10.2215/CJN.19611220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216620PMC
June 2021

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass.

Kidney Int 2021 06 8;99(6):1478-1486. Epub 2021 Apr 8.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; National Institute of Health Research Leicester Biomedical Research Centre, University of Leicester, Leicester, UK; National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health, Loughborough University, Loughborough, UK. Electronic address:

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.
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http://dx.doi.org/10.1016/j.kint.2021.02.027DOI Listing
June 2021

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a six-month programme of cycling exercise during haemodialysis.

Nephrol Dial Transplant 2021 May 13. Epub 2021 May 13.

Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

Background: Intradialytic cycling (IDC) may provide cardiovascular benefit to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a six-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines (IL-6, IL-10, TNF-α, CRP and IL6/IL-10), and their associations with physical activity, fitness and cardiovascular outcomes.

Methods: Participants were randomised to either a six-month programme of IDC (thrice weekly, moderate intensity cycling at RPE 12-14) in addition to usual care (n = 46), or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at six months.

Results: There was no significant (P=0.137) difference in circulating endotoxin between groups at 6-months (IDC group: 0.34±0.08 EU/mL; control group: 0.37±0.07 EU/mL). There were no significant between group difference in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP, and IL-6/IL-10.

Conclusions: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.
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http://dx.doi.org/10.1093/ndt/gfab178DOI Listing
May 2021

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

Clin Kidney J 2021 May 10;14(5):1345-1355. Epub 2020 Sep 10.

School of Health Sciences, Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, UK.

Background: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK.

Methods: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke's Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team.

Results: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry.

Conclusion: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally.

Trial Registration: ISRCTN N83508514; registered on 17 December 2014.
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http://dx.doi.org/10.1093/ckj/sfaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087141PMC
May 2021

Association of sarcopenia with mortality and end-stage renal disease in those with chronic kidney disease: a UK Biobank study.

J Cachexia Sarcopenia Muscle 2021 Jun 5;12(3):586-598. Epub 2021 May 5.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK.

Background: Sarcopenia, a degenerative and generalized skeletal muscle disorder involving the loss of muscle function and mass, is an under-recognized problem in clinical practice, particularly in chronic kidney disease (CKD). We aimed to investigate the prevalence of sarcopenia in individuals with CKD, its risk factors, and its association with all-cause mortality and progression to end-stage renal disease (ESRD).

Methods: UK Biobank participants were grouped according to the presence of CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m ) and as having probable (low handgrip strength), confirmed (plus low muscle mass), and severe sarcopenia (plus poor physical performance) based on the 2019 European Working Group of Sarcopenia in Older People and Foundation for the National Institutes of Health criteria. Risk factors were explored using logistic regression analysis. Survival models were applied to estimate risk of mortality and ESRD.

Results: A total of 428 320 participants, of which 8767 individuals with CKD (46% male, aged 62.8 (standard deviation 6.8) years, median estimated glomerular filtration rate 54.5 (interquartile range 49.0-57.7) mL/min/1.72 m ) were included. Probable sarcopenia was present in 9.7% of individuals with CKD compared with 5.0% in those without (P < 0.001). Sarcopenia was associated with being older; inflammation; poorer renal function; and lower serum albumin, total testosterone, and haemoglobin. The largest risk factors for sarcopenia were having three or more comorbidities (odds ratio: 2.30; 95% confidence interval: 1.62 to 3.29; P < 0.001) and physical inactivity: participants in the highest quartile of weekly activity were 43% less likely to have sarcopenia compared to the lowest quartile (odds ratio: 0.57; 0.42 to 0.76; P < 0.001). Participants with CKD and sarcopenia had a 33% (7% to 66%; P = 0.011) higher hazard of mortality compared with individuals without. Sarcopenic CKD individuals had a 10 year survival probability of 0.85 (0.82 to 0.88) compared with 0.89 (0.88 to 0.30) in those without sarcopenia, an absolute difference of 4%. Those with sarcopenia were twice as likely to develop ESRD (hazard ratio: 1.98; 1.45 to 2.70; P < 0.001).

Conclusions: Participants with reduced kidney function are at an increased risk of premature mortality. The presence of sarcopenia increases the risk of mortality and ESRD. Appropriate measurement of sarcopenia should be used to identify at-risk individuals. Interventions such as physical activity should be encouraged to mitigate sarcopenia.
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http://dx.doi.org/10.1002/jcsm.12705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200422PMC
June 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

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

BMC Nephrol 2021 Apr 22;22(1):147. Epub 2021 Apr 22.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK.

Background: Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population.

Methods: Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom.

Results: In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was 'feeling tired'; and 4) being female independently increased the likelihood of reporting more symptoms.

Conclusions: Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue.

Trial Registration: The study was registered prospectively as ISRCTN11596292 .
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http://dx.doi.org/10.1186/s12882-021-02355-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063370PMC
April 2021

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

Ultrason Imaging 2021 May 15;43(3):139-148. Epub 2021 Apr 15.

Department of Health Sciences, University of Leicester, Leicester, UK.

Chronic kidney disease (CKD) is characterized by progressive reductions in skeletal muscle function and size. The concept of muscle quality is increasingly being used to assess muscle health, although the best means of assessment remains unidentified. The use of muscle echogenicity is limited by an inability to be compared across devices. Gray level of co-occurrence matrix (GLCM), a form of image texture analysis, may provide a measure of muscle quality, robust to scanner settings. This study aimed to identify GLCM values from skeletal muscle images in CKD and investigate their association with physical performance and strength (a surrogate of muscle function). Transverse images of the rectus femoris muscle were obtained using B-mode 2D ultrasound imaging. Texture analysis (GLCM) was performed using ImageJ. Five different GLCM features were quantified: energy or angular second moment (ASM), entropy, homogeneity, or inverse difference moment (IDM), correlation, and contrast. Physical function and strength were assessed using tests of handgrip strength, sit to stand-60, gait speed, incremental shuttle walk test, and timed up-and-go. Correlation coefficients between GLCM indices were compared to each objective functional measure. A total of 90 CKD patients (age 64.6 (10.9) years, 44% male, eGFR 33.8 (15.7) mL/minutes/1.73 m) were included. Better muscle function was largely associated with those values suggestive of greater image texture homogeneity (i.e., greater ASM, correlation, and IDM, lower entropy and contrast). Entropy showed the greatest association across all the functional assessments ( = -.177). All GLCM parameters, a form of higher-order texture analysis, were associated with muscle function, although the largest association as seen with image entropy. Image homogeneity likely indicates lower muscle infiltration of fat and fibrosis. Texture analysis may provide a novel indicator of muscle quality that is robust to changes in scanner settings. Further research is needed to substantiate our findings.
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http://dx.doi.org/10.1177/01617346211009788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114433PMC
May 2021

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

Health Expect 2021 Jun 9;24(3):843-852. Epub 2021 Apr 9.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK.

Background: Patient activation describes the knowledge, skills and confidence in managing one's own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes.

Design: Cross-sectional study.

Setting And Participants: Patients with non-dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK.

Outcome Measures: Patient activation was measured using the PAM-13. Demographic and health-related variables, self-reported symptom burden, health-related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia.

Results: 743 patients were included (eGFR: 32.3 ( 17.1) mL/min/1.73 m , age 67.8 ( 13.9) years, 68% male). The mean PAM score was 55.1 ( 14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P = .004), greater number of comorbidities (P = .026) and lower haemoglobin (P = .025). Patients with low activation had a 17% greater number of CVD risk factors (P < .001). Risk factors in those with low activation were being older (P < .001) and having diabetes (P < .001).

Conclusion: This study showed that only a minority of CKD patients are activated for self-management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation.

Patient Or Public Contribution: Patients were involved in the design of main study.
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http://dx.doi.org/10.1111/hex.13225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235879PMC
June 2021

Evaluation of an 8-Week Vegan Diet on Plasma Trimethylamine-N-Oxide and Postchallenge Glucose in Adults with Dysglycemia or Obesity.

J Nutr 2021 Jul;151(7):1844-1853

Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, United Kingdom.

Background: Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health.

Objectives: We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia.

Methods: This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight.

Results: TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8.

Conclusions: These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988.
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http://dx.doi.org/10.1093/jn/nxab046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245890PMC
July 2021

Perceptions of exercise benefits and barriers: the influence on physical activity behaviour in individuals undergoing haemodialysis and peritoneal dialysis.

J Nephrol 2021 Mar 26. Epub 2021 Mar 26.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, LE17RH, UK.

Background: Despite growing evidence about the benefits of physical activity and exercise in patients receiving dialysis, physical inactivity is highly prevalent. This may be due to uncertainty and lack of appropriate guidance about exercise, or driven by the relative barriers and benefits that patients perceive. Understanding these perceptions in dialysis patients may inform interventions aimed to increase exercise participation.

Methods: Perceived benefits and barriers to exercise were measured by the 'Dialysis Patient-perceived Exercise Benefits and Barriers Scale' (DPEBBS). Self-reported physical activity status was assessed by the 'General Practice Physical Activity Questionnaire'. Barriers and benefits to exercise were classed as binary variables (i.e. yes and no). Frequency analyses and chi-squared tests were conducted to compare the differences perceived by people on haemodialysis (HD) and peritoneal dialysis (PD). Binominal logistical regression was performed to determine which perceived barriers and benefits had the biggest impact on physical activity status.

Results: One thousand twenty-two HD and 124 PD patients completed the DPEBBS. A greater proportion of HD than PD patients reported 'reduces body pain' (P = 0.013), 'delays decline in body function' (P = 0.01), and 'improves quality of life' (P = 0.033) as benefits of exercise. No differences in barriers were observed. Tiredness was the most reported barrier to exercise. Patients who perceived 'other comorbidities' (OR 3.389, P < 0.001) or 'burden of family' (OR 3.168, P < 0.001) as barriers were 3 times more likely to be inactive.

Conclusions: Dialysis patients perceive several barriers which may prevent them from engaging in physical activity. Addressing these barriers may be key to increasing participation in physical activity and exercise.
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http://dx.doi.org/10.1007/s40620-021-01024-yDOI Listing
March 2021

Reply: Ad Hoc Measurements of the Anterior Thigh Muscle (Mass and Function) in Sarcopenia.

J Ultrasound Med 2021 Mar 24. Epub 2021 Mar 24.

Department of Health Sciences, University of Leicester, Leicester, UK.

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http://dx.doi.org/10.1002/jum.15697DOI Listing
March 2021

Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis.

J Steroid Biochem Mol Biol 2021 Jun 3;210:105861. Epub 2021 Mar 3.

Department of Health Sciences, University of Leicester, United Kingdom.

Background: Evidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients.

Methods: This is a secondary cross-sectional analysis of previously published interventional study, with in vitro follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3 mL/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n = 20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors.

Results: In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with V̇O was seen with total vitamin D (25OHD). in vitro, 1α,25(OH)D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter.

Conclusions: Vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105861DOI Listing
June 2021

Physical activity and living well with kidney disease.

Nat Rev Nephrol 2021 03;17(3):145-146

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK.

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http://dx.doi.org/10.1038/s41581-021-00398-3DOI Listing
March 2021

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

J Sports Sci 2021 May 18;39(10):1174-1185. Epub 2020 Dec 18.

Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK.

Skeletal muscle atrophy, dysfunction, and weakness are consequences of noncommunicable diseases which result in exercise and functional limitations which contribute to poor quality of life and increased mortality. Home-based resistance training may promote skeletal muscle health. Electronic-based systematic searches were performed identifying randomised controlled trials utilising home-based resistance training in patients with noncommunicable diseases defined as cancer, cardiovascular disease, diabetes mellitus (type 1 and 2), chronic kidney disease (including dialysis), and chronic respiratory disease (asthma, chronic obstructive pulmonary disease, pulmonary hypertension). A comparator group was defined as one containing "non-exercise" or "usual care". Of the 239 studies identified (published between 1996 and 2020), 22 met the inclusion criteria. Sixteen studies contained an adjunct aerobic training component. Study designs and outcome measures showed large variation. Reporting of the principles of training applied within interventions was poor. Heterogeneity in study characteristics, and poor reporting of training characteristics, prevents formal recommendations for optimising home-based resistance training. However, home-based interventions are less resource-intensive than supervised programmes and appear to have the ability to improve or preserve pertinent outcomes such as strength, functional ability, and quality of life; potentially reducing the risk of mortality in patients with chronic disease.
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http://dx.doi.org/10.1080/02640414.2020.1861741DOI Listing
May 2021

The validity of the 'General Practice Physical Activity Questionnaire' against accelerometery in patients with chronic kidney disease.

Physiother Theory Pract 2020 Dec 2:1-10. Epub 2020 Dec 2.

Department of Health Sciences, Leicester Kidney Lifestyle Team, University of Leicester, Leicester, UK.

: The majority of patients with chronic kidney disease (CKD) are physically inactive. Simple yet accurate assessment of physical activity is important in identifying those in need of intervention. The 'General Practice Physical Activity Questionnaire' (GPPAQ) is a well-used clinical and research tool, but has not been validated.: Forty individuals with CKD (age 62.5 (SD: 11.1) years, estimated glomerular filtration rate (eGFR) 33.2 (SD:19.1) ml/min/1.73 m) completed the GPPAQ and objective physical activity was measured using a GENEActiv accelerometer for 7 days. Physical activity status was grouped as 'Active' (i.e. meeting current physical activity UK guidelines) or 'Inactive.' Sensitivity and specificity were calculated. Accuracy was defined as the probability the GPPAQ could correctly classify a patient as either 'Active' or 'Inactive' (based on accelerometery).: Using accelerometery, 18% of participants met the current UK guidelines, whereas 27% were classed as 'Active' according to GPPAQ. Sensitivity of the GPPAQ was 54.6% and specificity was 96.6%. The 'accuracy' of the GPPAQ was 85.0%. The accuracy of the GPPAQ was greater in males and those not in employment/retired, although these differences were not statistically significant.: The GPPAQ may be a useful tool to identify CKD patients who would benefit most from a physical activity intervention. In particular, the GPPAQ can accurately identify those not sufficiently active.
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http://dx.doi.org/10.1080/09593985.2020.1855684DOI Listing
December 2020

Exercise for people living with frailty and receiving haemodialysis: a mixed-methods randomised controlled feasibility study.

BMJ Open 2020 11 3;10(11):e041227. Epub 2020 Nov 3.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Objectives: Frailty is highly prevalent in haemodialysis (HD) patients, leading to poor outcomes. This study aimed to determine whether a randomised controlled trial (RCT) of intradialytic exercise is feasible for frail HD patients, and explore how the intervention may be tailored to their needs.

Design: Mixed-methods feasibility.

Setting And Participants: Prevalent adult HD patients of the trial with a Clinical Frailty Scale Score of 4-7 (vulnerable to severely frail) were eligible for the feasibility study.

Interventions: Participants in the exercise group undertook 6 months of three times per week, progressive, moderate intensity intradialytic cycling (IDC).

Outcomes: Primary outcomes were related to feasibility. Secondary outcomes were falls incidence measured from baseline to 1 year following intervention completion, and exercise capacity, physical function, physical activity and patient-reported outcomes measured at baseline and 6 months. Acceptability of trial procedures and the intervention were explored via diaries and interviews with n=25 frail HD patients who both participated in (n=13, 52%), and declined (n=12, 48%), the trial.

Results: 124 (30%) patients were eligible, and of these 64 (52%) consented with 51 (80%) subsequently completing a baseline assessment. n=24 (71% male; 59±13 years) dialysed during shifts randomly assigned to exercise and n=27 (81% male; 65±11 years) shifts assigned to usual care. n=6 (12%) were lost to follow-up. The exercise group completed 74% of sessions. 27%-89% of secondary outcome data were missing. Frail HD patients outlined several ways to enhance trial procedures. Maintaining ability to undertake activities of daily living and social participation were outcomes of primary importance. Participants desired a varied exercise programme.

Conclusions: A definitive RCT is feasible, however a comprehensive exercise programme may be more efficacious than IDC in this population.

Trial Registration Numbers: ISRCTN11299707; ISRCTN12840463.
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http://dx.doi.org/10.1136/bmjopen-2020-041227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640592PMC
November 2020

Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving Hemodialysis: The SONG-HD Fatigue Instrument.

Clin J Am Soc Nephrol 2020 11 22;15(11):1614-1621. Epub 2020 Oct 22.

Faculty of Science, Quality of Life Office, School of Psychology, University of Sydney, Sydney, Australia.

Background And Objectives: Fatigue is a very common and debilitating symptom and identified by patients as a critically important core outcome to be included in all trials involving patients receiving hemodialysis. A valid, standardized measure for fatigue is needed to yield meaningful and relevant evidence about this outcome. This study validated a core patient-reported outcome measure for fatigue in hemodialysis.

Design, Setting, Participants, & Measurements: A longitudinal cohort study was conducted to assess the validity and reliability of a new fatigue measure (Standardized Outcomes in Nephrology-Hemodialysis Fatigue [SONG-HD Fatigue]). Eligible and consenting patients completed the measure at three time points: baseline, a week later, and 12 days following the second time point. Cronbach and intraclass correlation coefficient were calculated to assess internal consistency, and Spearman rho was used to assess convergent validity. Confirmatory factor analysis was also conducted. Hemodialysis units in the United Kingdom, Australia, and Romania participated in this study. Adult patients aged 18 years and over who were English speaking and receiving maintenance hemodialysis were eligible to participate. Standardized Outcomes in Nephrology-Hemodialysis, the Visual Analog Scale for fatigue, the 12-Item Short Form Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue were used.

Results: In total, 485 participants completed the study across the United Kingdom, Australia, and Romania. Psychometric assessment demonstrated that Standardized Outcomes in Nephrology-Hemodialysis is internally consistent (Cronbach =0.81-0.86) and stable over a 1-week period (intraclass correlation coefficient =0.68-0.74). The measure demonstrated convergence with Functional Assessment of Chronic Illness Therapy-Fatigue and had moderate correlations with other measures that assessed related but not the same concept (the 12-Item Short Form Survey and the Visual Analog Scale). Confirmatory factor analysis supported the one-factor model.

Conclusions: SONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.
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http://dx.doi.org/10.2215/CJN.05880420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646231PMC
November 2020

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

J Ultrasound Med 2021 Mar 11;40(3):457-467. Epub 2020 Aug 11.

Departments of Health Sciences, University of Leicester, Leicester, UK.

Objectives: Patients with chronic kidney disease (CKD) have aberrant changes in body composition, including low skeletal muscle mass, a feature of "sarcopenia." The measurement of the (quadriceps) rectus femoris (RF) cross-sectional area (CSA) is widely used as a marker of muscle size. Cutoff values are needed to help discriminate the condition of an individual's muscle (eg, presence of sarcopenia) quickly and accurately. This could help distinguish those at greater risk and aid in targeted treatment programs.

Methods: Transverse images of the RF were obtained by B-mode 2-dimensional ultrasound imaging. Sarcopenic levels of muscle mass were defined by established criteria (1, appendicular skeletal muscle mass [ASM]; 2, ASM/height ; and 3, ASM/body mass index) based on the ASM and total muscle mass measured by a bioelectrical impedance analysis. The discriminative power of RF-CSA was assessed by receiver operating characteristic curves, and optimal cutoffs were determined by the maximum Youden index (J).

Results: One hundred thirteen patients with CKD (mean age [SD], 62.0 [14.1] years; 48% male; estimated glomerular filtration rate, 38.0 [21.5] mL/min/1.73m ) were included. The RF-CSA was a moderate predictor of ASM (R = 0.426; P < .001) and total muscle mass (R = 0.438; P < .001). With a maximum J of 0.47, in male patients, an RF-CSA cutoff of less than 8.9 cm was deemed an appropriate cutoff for detecting sarcopenic muscle mass. In female patients, an RF-CSA cutoff of less than 5.7 cm was calculated on the basis of ASM/height (J = 0.71).

Conclusions: Ultrasound may provide a low-cost and simple means to diagnose sarcopenia in patients with CKD. This would allow for early management and timely intervention to help mitigate the effects in this group.
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http://dx.doi.org/10.1002/jum.15421DOI Listing
March 2021

The association of muscle size, strength and exercise capacity with all-cause mortality in non-dialysis-dependent CKD patients.

Clin Physiol Funct Imaging 2020 Nov 9;40(6):399-406. Epub 2020 Aug 9.

Department of Health Sciences, University of Leicester, Leicester, UK.

Background/objective: Patients with chronic kidney disease (CKD) are commonly reported to exhibit skeletal muscle wasting, reduced strength and exercise capacity. Evidence from patients with end-stage renal disease (ESRD) demonstrates these factors are associated with mortality, but it is unclear whether this relationship exists earlier in the illness. Our objective was to determine whether muscle size, strength or exercise capacity was associated with all-cause mortality, unscheduled hospital admissions or time to ESRD in patients not requiring dialysis.

Methods: This is a prospective cohort study of 89 patients with CKD stages 3b-5 not requiring renal replacement therapy with a mean follow-up period of 3.3 years in which the contribution of predictors of rectus femoris muscle size, muscle strength, exercise capacity to all-cause mortality rates, progression to ESRD and time to first hospitalization were investigated.

Results: Unadjusted analysis suggested each 1 cm increase in quadriceps muscle size (measured by ultrasonography cross-sectional area) was associated with a 38% reduced risk for death (p = .006), and a 10 m improvement on the incremental shuttle walk test was associated with a 3% reduced risk for death (p = .04). However, this relationship was not present in analysis adjusted for age, gender and eGFR. No association was seen between any factor for the development of ESRD or time to first hospitalization.

Conclusion: These results suggest that in this small cohort, muscle size and exercise capacity are associated with mortality when considered alone, but this relationship was not present in adjusted analyses. Further investigation in a larger patient group is warranted.
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http://dx.doi.org/10.1111/cpf.12655DOI Listing
November 2020

Impact of physical activity and exercise on bone health in patients with chronic kidney disease: a systematic review of observational and experimental studies.

BMC Nephrol 2020 08 8;21(1):334. Epub 2020 Aug 8.

Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University Institute of Maia, Av. Carlos Oliveira Campos - Castelo da Maia, 4475-690, Maia, Portugal.

Background: Chronic Kidney Disease (CKD) patients frequently develop life-impairing bone mineral disorders. Despite the reported impact of exercise on bone health, systematic reviews of the evidence are lacking. This review examines the association of both physical activity (PA) and the effects of different exercise interventions with bone outcomes in CKD.

Methods: English-language publications in EBSCO, Web of Science and Scopus were searched up to May 2019, from which observational and experimental studies examining the relation between PA and the effect of regular exercise on bone-imaging or -outcomes in CKD stage 3-5 adults were included. All data were extracted and recorded using a spreadsheet by two review authors. The evidence quality was rated using the Cochrane risk of bias tool and a modified Newcastle-Ottawa scale.

Results: Six observational (4 cross-sectional, 2 longitudinal) and seven experimental (2 aerobic-, 5 resistance-exercise trials) studies were included, with an overall sample size of 367 and 215 patients, respectively. Judged risk of bias was low and unclear in most observational and experimental studies, respectively. PA was positively associated with bone mineral density at lumbar spine, femoral neck and total body, but not with bone biomarkers. Resistance exercise seems to improve bone mass at femoral neck and proximal femur, with improved bone formation and inhibited bone resorption observed, despite the inconsistency of results amongst different studies.

Conclusions: There is partial evidence supporting (i) a positive relation of PA and bone outcomes, and (ii) positive effects of resistance exercise on bone health in CKD. Prospective population studies and long-term RCT trials exploring different exercise modalities measuring bone-related parameters as endpoint are currently lacking.
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http://dx.doi.org/10.1186/s12882-020-01999-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414574PMC
August 2020

Response of the oxygen uptake efficiency slope to exercise training in patients with chronic kidney disease.

Kidney Res Clin Pract 2020 Sep;39(3):305-317

Leicester Kidney Lifestyle Team, Department of Health Science, University of Leicester, Leicester, UK.

Background: Chronic kidney disease (CKD) patients have poor cardiorespiratory fitness. Although cardiopulmonary exercise testing (CPET) is a universal assessment of cardiorespiratory fitness, values taken at 'peak' effort are strongly influenced by motivation and the choice of test endpoint. The oxygen uptake efficiency slope (OUES) integrates cardiovascular, musculoskeletal, and respiratory function into a single index to provide a more pragmatic and safer alternative to maximal testing. No research has explored whether exercise can improve the OUES in CKD patients.

Methods: Thirty-two patients with non-dialysis CKD were recruited into a 12-week exercise program consisting of mixed aerobic and resistance training three times a week. CPET was conducted at baseline, and then, following a 6-week control period, at pre- and post-exercise intervention. Direct measurements of oxygen consumption (V̇O2) and ventilatory parameters were collected. The OUES was calculated as the relationship between V̇O2 and the log of minute ventilation (V̇E).

Results: No changes were observed in any variable during the control period, although modest increases in V̇O were observed. No meaningful changes were observed as a result of exercise in any cardiorespiratory value obtained. The OUES calculated at 100%, 90%, 75%, and 50% of exercise duration did not change significantly after 12 weeks of exercise training.

Conclusion: Our results show that 12 weeks of exercise training had no beneficial effects on the OUES, which supports the modest change observed in V̇O2. The lack of change in the OUES and other parameters could indicate a dysfunctional cardiorespiratory response to exercise in patients with CKD, likely mediated by dysfunctional peripheral metabolic mechanisms.
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http://dx.doi.org/10.23876/j.krcp.20.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530363PMC
September 2020

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

FASEB J 2020 01 6;34(1):1755-1767. Epub 2019 Dec 6.

Department of Health Sciences, University of Leicester, Leicester, UK.

Patients with chronic kidney disease (CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clearly defined but may involve reductions in mitochondrial function, mass and biogenesis. Here we report on the effect of non-dialysis dependent CKD (NDD-CKD) on mitochondrial mass and basal expression of transcription factors involved in mitochondrial biogenesis compared to a healthy control cohort (HC). In addition, we sought to investigate the effect of a 12-week exercise-training programme on these aspects of mitochondrial dysfunction in a NDD-CKD cohort.For the comparison between NDD-CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis (VL) of n=16 non-dialysis dependent CKD patient's stage 3b-5 (NDD-CKD) and n=16 healthy controls matched for age, gender and physical activity (HC). To investigate the effect of exercise training, VL biopsies were collected from n=17 NDD-CKD patients before and after a 12-week exercise intervention that was comprised of aerobic exercise (AE) or a combination of aerobic exercise and resistance training (CE). Mitochondrial mass was analysed by citrate synthase activity and mitochondrial protein content by Porin expression, whilst the expression of transcription factors involved in mitochondrial biogenesis were quantified by real-time qPCR. NDD-CKD patients exhibited a significant reduction in mitochondrial mass when compared to HC, coupled to a reduction in PGC-1α, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression. 12-weeks of exercise training resulted in a significant increase in PGC-1α expression in both groups, with no further changes seen across indicators of mitochondrial biogenesis. No significant changes in mitochondrial mass were observed in response to either exercise programme. NDD-CKD patients exhibit reduced skeletal muscle mitochondrial mass and gene expression of transcription factors involved in mitochondrial biogenesis compared to HC. These reductions were not restored following 12-weeks of exercise training implying exercise resistance in this cohort. The reasons for this lack of improvement are currently unknown and require further investigation, as reversing the dysregulation of these processes in NDD-CKD may provide a therapeutic opportunity to improve muscle fatigue and dysfunction in this population.
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http://dx.doi.org/10.1096/fj.201901936RRDOI Listing
January 2020

Standardising the measurement of physical activity in people receiving haemodialysis: considerations for research and practice.

BMC Nephrol 2019 12 4;20(1):450. Epub 2019 Dec 4.

Department of Respiratory Science, University of Leicester, Leicester Kidney Lifestyle Team, Academic Unit, Leicester General Hospital, Gwendolen Road, Leicester, LE4 5PW, UK.

Background: Physical activity (PA) is exceptionally low amongst the haemodialysis (HD) population, and physical inactivity is a powerful predictor of mortality, making it a prime focus for intervention. Objective measurement of PA using accelerometers is increasing, but standard reporting guidelines essential to effectively evaluate, compare and synthesise the effects of PA interventions are lacking. This study aims to (i) determine the measurement and processing guidance required to ensure representative PA data amongst a diverse HD population, and; (ii) to assess adherence to PA monitor wear amongst HD patients.

Methods: Clinically stable HD patients from the UK and China wore a SenseWear Armband accelerometer for 7 days. Step count between days (HD, Weekday, Weekend) were compared using repeated measures ANCOVA. Intraclass correlation coefficients (ICCs) determined reliability (≥0.80 acceptable). Spearman-Brown prophecy formula, in conjunction with a priori ≥  80% sample size retention, identified the minimum number of days required for representative PA data.

Results: Seventy-seven patients (64% men, mean ± SD age 56 ± 14 years, median (interquartile range) time on HD 40 (19-72) months, 40% Chinese, 60% British) participated. Participants took fewer steps on HD days compared with non-HD weekdays and weekend days (3402 [95% CI 2665-4140], 4914 [95% CI 3940-5887], 4633 [95% CI 3558-5707] steps/day, respectively, p < 0.001). PA on HD days were less variable than non-HD days, (ICC 0.723-0.839 versus 0.559-0.611) with ≥ 1 HD day and ≥  3 non-HD days required to provide representative data. Using these criteria, the most stringent wear-time retaining ≥ 80% of the sample was ≥7 h.

Conclusions: At group level, a wear-time of ≥7 h on ≥1HD day and ≥ 3 non-HD days is required to provide reliable PA data whilst retaining an acceptable sample size. PA is low across both HD and non- HD days and future research should focus on interventions designed to increase physical activity in both the intra and interdialytic period.
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http://dx.doi.org/10.1186/s12882-019-1634-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894215PMC
December 2019

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

Am J Physiol Renal Physiol 2020 01 18;318(1):F76-F85. Epub 2019 Nov 18.

Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min·1.73 m (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min·1.73 m, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min·1.73 m) completed 20 min of walking at 60-70% peak O consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical ( = 0.001) and nonclassical ( = 0.002) monocyte subset proportions but decreased the intermediate subset ( < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups ( = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).
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http://dx.doi.org/10.1152/ajprenal.00332.2019DOI Listing
January 2020
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