Participant acceptability of exercise in kidney disease (PACE-KD): a feasibility study protocol in renal transplant recipients.

INTRODUCTION: Cardiovascular disease (CVD) is a major cause of mortality in renal transplant recipients (RTRs). General population risk scores for CVD underestimate the risk in patients with chronic kidney disease (CKD) suggesting additional non-traditional factors. Renal transplant recipients also exhibit elevated inflammation and impaired immune function. Exercise has a positive impact on these factors in patients with CKD but there is a lack of rigorous research in RTRs, particularly surrounding the feasibility and acceptability of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in this population. This study aims to explore the feasibility of three different supervised aerobic exercise programmes in RTRs to guide the design of future large-scale efficacy studies. METHODS AND ANALYSIS: Renal transplant recipients will be randomised to HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%-90% of peak oxygen uptake (VO2 peak)), HIIT B (4×4 min interval training at 80%-90% VO2peak) or MICT (~40 min cycling at 50%-60% VO2peak) where they will undertake 24 supervised sessions (approximately thrice weekly over 8 weeks). Assessment visits will be at baseline, midtraining, immediate post-training and 3 months post-training. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the implementation of the interventions. A further qualitative sub-study QPACE-KD (Qualitative Participant Acceptability of Exercise in Kidney Disease) will explore patient experiences and perspectives through semistructured interviews and focus groups. ETHICS AND DISSEMINATION: All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, public platforms and academic publications. TRIAL REGISTRATION NUMBER: Prospectively registered; ISRCTN17122775

Postural stability during standing and its association with physical and cognitive functions in non-dialysis chronic kidney disease patients.

PURPOSE: Chronic kidney disease (CKD) is characterised by poor physical function. A possible factor may be aberrant changes to balance and postural stability (i.e. ability to maintain centre of pressure (COP)). Previous research has exclusively focused on patients undergoing renal replacement therapy (RRT). The current study investigated postural stability in a group of CKD patients not requiring RRT. METHODS: 30 CKD patients (aged 57.0 ± 17.8 years, 47% female, mean eGFR 42.9 ± 27.2 ml/kg/1.73 m2) underwent a series of physical function assessments including the sit-to-stand-5 and -60, incremental shuttle walk test, gait speed, and short physical performance battery. Postural stability (defined as total COP ellipse (mm2) displacement) was measured using the Fysiometer board. Control reference data were provided by the manufacture. Cognitive function was assessed using the 'Montreal Cognitive Assessment-Basic' (MOCA-B)'. RESULTS: CKD patients had poorer postural stability during quiet standing than reference values across all age categories (≤ 39 years, 24.9 ± 11.3 vs. 10.4 ± 1.8 mm2; 40-59 years, 34.3 ± 19.0 vs. 17.7 ± 6.2 mm2; ≥ 60 years, 39.7 ± 21.2 vs. 16.8 ± 2.9 mm2, all comparisons P < 0.001). Reductions in postural stability were associated with both physical and cognitive functioning. In females only, postural stability worsened with declining renal function (r = - 0.790, P < 0.01). CONCLUSIONS: To our knowledge, this is the first and largest experimental report concerning measurement of postural stability of CKD patients not requiring RRT. Our findings suggest that postural stability is associated with worse physical and cognitive functioning in this patient group

Physical activity, immune function and inflammation in kidney patients (the PINK study): a feasibility trial protocol.

INTRODUCTION: Patients with chronic kidney disease (CKD) display increased infection-related mortality and elevated cardiovascular risk only partly attributed to traditional risk factors. Patients with CKD also exhibit a pro-inflammatory environment and impaired immune function. Aerobic exercise has the potential to positively impact these detriments, but is under-researched in this patient population. This feasibility study will investigate the effects of acute aerobic exercise on inflammation and immune function in patients with CKD to inform the design of larger studies intended to ultimately influence current exercise recommendations. METHODS AND ANALYSIS: Patients with CKD, including renal transplant recipients, will visit the laboratory on two occasions, both preceded by appropriate exercise, alcohol and caffeine restrictions. On visit 1, baseline assessments will be completed, comprising anthropometrics, body composition, cardiovascular function and fatigue and leisure time exercise questionnaires. Participants will then undertake an incremental shuttle walk test to estimate predicted peak O2 consumption (VO2peak). On visit 2, participants will complete a 20 min shuttle walk at a constant speed to achieve 85% estimated VO2peak. Blood and saliva samples will be taken before, immediately after and 1 hour after this exercise bout. Muscle O2 saturation will be monitored throughout exercise and recovery. Age and sex-matched non-CKD 'healthy control' participants will complete an identical protocol. Blood and saliva samples will be analysed for markers of inflammation and immune function, using cytometric bead array and flow cytometry techniques. Appropriate statistical tests will be used to analyse the data. ETHICS AND DISSEMINATION: A favourable opinion was granted by the East Midlands-Derby Research Ethics Committee on 18 September 2015 (ref 15/EM/0391), and the study was approved and sponsored by University Hospitals of Leicester Research and Innovation (ref 11444). The study was registered with ISRCTN (ref 38935454). The results will be presented at relevant conferences, and it is anticipated that the reports will be published in appropriate journals in 2018

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

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

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

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

Association of Ethnicity and Socioeconomic Status With COVID-19 Hospitalization and Mortality in Those With and Without Chronic Kidney Disease

In the United Kingdom, as of December 2021, there have been more than 11.5 million confirmed cases of COVID-19 and more than 170,000 deaths caused by SARS-CoV-2.S1 Data are being reported on subpopulations most at risk of COVID-19 and its most severe forms. Age, ethnicity, and socioeconomic position—fundamental components in health inequality—strongly influence health outcomes for both infectious and noncommunicable diseases, and COVID-19 has further exposed the strong association between these and adverse health outcomes.1There is substantial evidence that a disproportionate impact of COVID-19 exists on Black and South Asian ethnic groups.S2 Individuals from these groups are more likely to be infected by SARS-CoV-2 and have an increased risk of intensive care admission compared with those of White ethnicity.2 The mortality risk from COVID-19 among Black and Asian ethnic minority groups is approximately twice that of White patients.1,3 Socioeconomic status is also a key factor in COVID-19 outcome,4 and mortality rates from COVID-19 in the most deprived areas are more than double that of least deprived areas.5Many of the ethnic and socioeconomic disparities that increase susceptibility to COVID-19 also make individuals vulnerable to chronic kidney disease (CKD). The risk of CKD is higher in ethnic minority groups compared with White individuals at every CKD stage,6 and CKD is associated with greater hospitalization and mortality from COVID-19.7,S3,S4 Although the etiology of CKD involvement is multifactorial,S3 the interactions with ethnic and socioeconomic status have not been studied. Previous data suggest that inequalities in COVID-19 deaths by ethnic group exist among people with similar pre-existing conditions, including CKD7; however, to our knowledge, no study has investigated how ethnicity and socioeconomic status affect COVID-19 severity among those with CKD.</div

Exercise during hemodialysis does not affect the phenotype or prothrombotic nature of microparticles but alters their proinflammatory function.

Hemodialysis patients have dysfunctional immune systems, chronic inflammation and comorbidity-associated risks of cardiovascular disease (CVD) and infection. Microparticles are biologically active nanovesicles shed from activated endothelial cells, immune cells, and platelets; they are elevated in hemodialysis patients and are associated with chronic inflammation and predictive of CVD mortality in this group. Exercise is advocated in hemodialysis to improve cardiovascular health yet acute exercise induces an increase in circulating microparticles in healthy populations. Therefore, this study aimed to assess acute effect of intradialytic exercise (IDE) on microparticle number and phenotype, and their ability to induce endothelial cell reactive oxygen species (ROS) in vitro. Eleven patients were studied during a routine hemodialysis session and one where they exercised in a randomized cross-over design. Microparticle number increased during hemodialysis (2064-7071 microparticles/μL, P < 0.001) as did phosphatidylserine+ (P < 0.05), platelet-derived (P < 0.01) and percentage procoagulant neutrophil-derived microparticles (P < 0.05), but this was not affected by IDE. However, microparticles collected immediately and 60 min after IDE (but not later) induced greater ROS generation from cultured endothelial cells (P < 0.05), suggesting a transient proinflammatory event. In summary IDE does not further increase prothrombotic microparticle numbers that occurs during hemodialysis. However, given acute proinflammatory responses to exercise stimulate an adaptation toward a circulating anti-inflammatory environment, microparticle-induced transient increases of endothelial cell ROS in vitro with IDE may indicate the potential for a longer-term anti-inflammatory adaptive effect. These findings provide a crucial evidence base for future studies of microparticles responses to IDE in view of the exceptionally high risk of CVD in these patients

Peak aerobic capacity from incremental shuttle walk test in chronic kidney disease.

BACKGROUND: Assessment of cardiorespiratory fitness is an important outcome in chronic kidney disease (CKD). We aimed to develop a predictive equation to estimate peak oxygen uptake (VO2peak ) and power output (WPeak ), as measured during a cardiopulmonary exercise test (CPET), from the distance walked (DW) during the incremental shuttle walk test (ISWT). METHODS: Thirty-six non-dialysing patients with CKD [17 male, age: 61 ± 12 years, eGFR: 25±7 ml/min/1.73 m2 , body mass index (BMI): 31 ± 6 kg/m2 ] carried out laboratory-based CPET on a cycle ergometer and ISWT on two separate occasions. RESULTS: Linear regression revealed that DW/BMI was a significant predictor of VO2Peak (r = 0.78) (VO2Peak (ml/min/kg) = [0.5688 × (DW/BMI) (m)] + 11.50). No difference (p = 0.66) between CPET VO2Peak (19.9 ± 5.5 ml/min/kg) and predicted VO2Peak (19.9 ± 4.3 ml/min/kg) was observed. DW multiplied by body mass (BM) was a significant predictor of WPeak (r = 0.80) [WPeak (W) = (0.0018 × (DW × BM)) + 50.47]. No difference (p = 0.97) between CPET WPeak (116.2 ± 38.9 W) and estimated WPeak (113.9 ± 30.1 W) was seen. CONCLUSION: The present study demonstrates that VO2Peak and WPeak can be accurately estimated using the DW during an ISWT in CKD populations

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

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

Symptom-burden in people living with frailty and chronic kidney disease

BackgroundFrailty is independently associated with worse health-related quality of life (HRQOL) in chronic kidney disease (CKD). However, the relationship between frailty and symptom experience is not well described in people living with CKD. This study’s aim was to evaluate the relationship between frailty and symptom-burden in CKD.MethodsThis study is a secondary analysis of a cross-sectional observational study, the QCKD study (ISRCTN87066351), in which participants completed physical activity, cardiopulmonary fitness, symptom-burden and HRQOL questionnaires. A modified version of the Frailty Phenotype, comprising 3 self-report components, was created to assess frailty status. Multiple linear regression was performed to assess the association between symptom-burden/HRQOL and frailty. Logistic regression was performed to assess the association between experiencing symptoms frequently and frailty. Principal Component Analysis was used to assess the experienced symptom clusters.ResultsA total of 353 patients with CKD were recruited with 225 (64%) participants categorised as frail. Frail participants reported more symptoms, had higher symptom scores and worse HRQOL scores. Frailty was independently associated with higher total symptom score and lower HRQOL scores. Frailty was also independently associated with higher odds of frequently experiencing 9 out of 12 reported symptoms. Finally, frail participants experienced an additional symptom cluster that included loss of appetite, tiredness, feeling cold and poor concentration.ConclusionsFrailty is independently associated with high symptom-burden and poor HRQOL in CKD. Moreover, people living with frailty and CKD have a distinctive symptom experience. Proactive interventions are needed that can effectively identify and address problematic symptoms to mitigate their impact on HRQOL.</div