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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 (n = 56 control subjects and n = 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., Graphical abstract

Background Acute kidney injury (AKI) can lead to chronic kidney disease, which results in poor long-term outcomes. There is plausibility that increased levels of physical activity may promote renal recovery post-AKI. This study aimed to investigate associations between physical activity levels and renal recovery following stage 3 AKI, and to assess the feasibility of measuring physical activity levels in this population. Methods Forty One hospitalised patients with AKI stage 3 were enrolled. Serum creatinine and estimated glomerular filtration rate (eGFR) were collected at 12 months prior to the development of AKI, during the hospital admission when the episode of AKI stage 3 occurred, and at 1-, 3- and 6-months post discharge. All participants completed the General Practice Activity Questionnaire (GPPAQ) to assess physical activity levels. A pedometer was also worn for 7 days immediately following discharge and at 6-months post discharge to ascertain an average daily step count. Feasibility outcomes including eligibility, recruitment and retention rates, and losses to follow up were also assessed. Results The average (± SD) baseline eGFR and median (IQR) serum creatinine was 71 ± 20 mL/min/1.73m2 and 85 (49) μmol/L respectively. A threefold increase in creatinine occurred during hospitalisation 436 (265) μmol/L. Greatest renal recovery occurred prior to discharge, with recovery continuing for a further three months. Inactive individuals (low GPPAQ scores) had consistently higher serum creatinine values compared to those who were active: 1 months 122 (111) μmol/L vs 70 (0) μmol/L, 6 months 112 (57) μmol/L vs 68 (0) μmol/L. Individuals with higher step counts also displayed better renal recovery 6-months post discharge (r = -0.600, p = 0.208). Conclusions Higher levels of physical activity are associated with improved renal recovery after 6- months following an episode of stage 3 AKI. A future randomised controlled trial is feasible and would be required to confirm these initial findings.

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 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.

The Risk Assessment and Prediction Tool (RAPT) was developed to predict patient discharge destination for arthroplasty operations. However, since Enhanced Recovery After Surgery (ERAS) programs have been utilized in the UK, the RAPT score has not been validated for use. The aim of the current study was to evaluate the predictive validity of the RAPT score in an ERAS environment with short length of stay. Data were compiled from 545 patients receiving a primary elective total hip or total knee arthroplasty in a district general hospital over 12 months. RAPT scores, length of stay, and discharge destinations were recorded. Patients were classified as low, intermediate, or high risk as per their RAPT score. Length of stay was significantly different between groups (p = 0.008), with low-risk patients having shorter length of stay. However, RAPT scores did not predict discharge destination; the overall correct prediction was only 31.9%. Furthermore, the most likely discharge destination was directly home in ≤3 days in all groups (68.5%, 60.2%, and 40% for the low-, intermediate-, and high-risk groups, respectively). The RAPT score is not an adequate tool to predict the discharge disposition following primary total knee and hip replacement surgery in a UK hospital with a standardized modern ERAS program. Alternative predictive tools are required.

Background and Aims Individuals with end-stage kidney disease receiving haemodialysis have elevated levels of circulating endotoxin as a result of changes to the intestinal barrier. These elevated levels are believed to play a role in the high levels of inflammation in this population. Programmes of cycling during dialysis (Intradialytic cycling (IDC)) can provide benefits to individuals receiving haemodialysis, but it is unclear how they may effect circulating levels of endotoxin. Therefore, the primary aim of this study is to investigate the effect of a 6-month programme of IDC on circulating endotoxin. Further aims are to investigate the associations between levels of physical activity and levels of circulating endotoxin and markers of inflammation in haemodialysis patients. Method This is a secondary analysis of the CYCLE-HD randomised controlled trial (ISRCTN11299707). Participants were randomised to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at RPE 12-14) in addition to usual care (n=46), or usual care (n=46) only. At baseline and 6 months blood samples were collected from the arterial needle immediately prior to haemodialysis therapy and following centrifugation stored at -80°C. Endotoxin, interleukin (IL)-6, IL-10, tumour necrosis factor-α (TNF-α) and high sensitivity C-reactive protein (Hs-CRP) were quantified using immunoassays. Levels of physical activity were measured using an accelerometer. Participants were instructed to wear the accelerometer for 7 days at baseline, and steps per day were calculated by dividing total steps by number of days worn . Results Steps per day data and endotoxin and inflammatory data was available for n=81 participants at baseline. There was a significant negative association between number of steps per day and IL-6 (P=0.001, R=-0.361), Hs-CRP (P Conclusion Higher levels of physical activity were associated with lower levels of circulating endotoxin, IL-6 and Hs-CRP in individuals receiving haemodialysis. A 6-month programme of IDC did not result in increases in circulating endotoxin, indicating that this physiological stress does not result in changes to the intestinal barrier in haemodialysis patients. Lastly, IDC did not appear to increase circulating markers of inflammation.

Background and Aims Acute kidney injury (AKI) is a known risk factor for the development of chronic kidney disease (CKD). Animal studies have demonstrated the potentially reno-protective effects of physical activity, both against the development of AKI and in promoting renal recovery. However, this has not been investigated in humans. The aim of the study was to investigate the association between physical activity levels and recovery in kidney function, measured by eGFR and creatinine, following an episode of stage 3 AKI. Method Twelve hospitalised participants with non-obstructive stage 3 AKI (as per KDIGO criteria) were asked to complete two questionnaires; the General Practitioner Physical Activity Questionnaire (GPPAQ), a measure of physical activity and; the Duke Activity Status Index, a measure of functional capacity. Baseline questionnaires were completed whilst in hospital (where participants were asked to recall their physical activity and functional capacity levels before hospitalisation) and again at 6-months post discharge. In addition, participants wore a pedometer for 7 consecutive days following discharge to ascertain their daily step count. Baseline renal function was collected using eGFR and creatinine measurements within the 12-months prior to admission; further readings were collected 25 ± 46 days after discharge as a measure of renal recovery (referred to as recovered creatinine). Results Data from the 12 participants who provided step count information were analysed. At diagnosis of stage 3 AKI, participants had a mean creatinine of 547 ± 280 with their mean baseline and recovered creatinine as follows; 95 ± 35 and 172 ± 83. A higher daily step count after discharge was associated with both a higher baseline eGFR (r=0.73, p Conclusion These results show a positive association between physical activity levels and renal recovery following an episode of AKI. This suggests that higher levels of physical activity may be protective and promote recovery of renal function following an episode of AKI. Physical activity and exercise interventions should be tested in the setting of AKI to see whether they are efficacious in promoting renal recovery.

Background Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes. Methods Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of ‘somewhat hard’. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise. Results Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P

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

Background/Aims: Patients requiring haemodialysis have cardiovascular and immune dysfunction. Little is known about the acute effects of exercise during haemodialysis. Exercise has numerous health benefits but in other populations has a profound impact upon blood pressure, inflammation and immune function; therefore having the potential to exacerbate cardiovascular and immune dysfunction in this vulnerable population. Methods: Fifteen patients took part in a randomised-crossover study investigating the effect of a 30-min bout of exercise during haemodialysis compared to resting haemodialysis. We assessed blood pressure, plasma markers of cardiac injury and systemic inflammation and neutrophil degranulation. Results: Exercise increased blood pressure immediately post-exercise; however, 1 hour after exercise blood pressure was lower than resting levels (106±22 vs. 117±25 mm Hg). No differences in h-FABP, cTnI, myoglobin or CKMB were observed between trial arms. Exercise did not alter circulating concentrations of IL-6, TNF-α or IL-1ra nor clearly suppress neutrophil function. Conclusions: This study demonstrates fluctuations in blood pressure during haemodialysis in response to exercise. However, since the fall in blood pressure occurred without evidence of cardiac injury, we regard it as a normal response to exercise superimposed onto the haemodynamic response to haemodialysis. Importantly, exercise did not exacerbate systemic inflammation or immune dysfunction; intradialytic exercise was well tolerated.

An increase in circulating monocyte and platelet derived microparticles during haemodialysis

Highly trained athletes are associated with high resting antigen-stimulated whole blood culture interleukin (IL)-10 production. The purpose of the present study was to examine the effects of training status on resting circulating T regulatory (Treg) cell counts and antigen-stimulated IL-10 production and the effect of acute bout of exercise on the Treg response. Forty participants volunteered to participate and were assigned to one of the four groups: sedentary (SED), recreationally active (REC), sprint-trained athletes and endurance-trained athletes (END). From the resting blood sample, CD4(+)CD25(+)CD127(low/-) Treg cells and in vitro antigen-stimulated IL-10 production were assessed. Ten REC subjects performed 60 min cycling at 70 % of maximal oxygen uptake and blood samples for Treg analysis were collected post- and 1 h post-exercise. IL-10 production was greater in END compared with the other groups (P0.05). END had a higher Treg percentage of total lymphocyte count compared with SED (P0.05). A smaller proportion of Treg CD4(+) cells were observed in SED compared with all other groups (P0.05). IL-10 production significantly correlated with the proportion of Tregs within the total lymphocyte population (r s = 0.51, P = 0.001). No effect of acute exercise was evident for Treg cell counts in the REC subjects (P0.05). Our results demonstrate that high training loads in END are associated with greater resting IL-10 production and Treg cell count and suggest a possible mechanism for depression of immunity commonly reported in athletes engaged in high training loads.

Background There is emerging evidence that exercise training could positively impact several of the cardiovascular risk factors associated with sudden cardiac death amongst patients on haemodialysis. The primary aim of this study is to evaluate the effect of an intradialytic exercise programme on left ventricular mass. Method and design Prospective, randomised cluster open-label blinded endpoint clinical trial in 130 patients with end stage renal disease on haemodialysis. Patients will be randomised 1:1 to either 1) minimum of 30 min continuous cycling thrice weekly during dialysis or 2) standard care. The primary outcome is change in left ventricular mass at 6 months, assessed by cardiac MRI (CMR). In order to detect a difference in LV mass of 15 g between groups at 80 % power, a sample size of 65 patients per group is required. Secondary outcome measures include abnormalities of cardiac rhythm, left ventricular volumes and ejection fraction, physical function measures, anthropometric measures, quality of life and markers of inflammation, with interim assessment for some measures at 3 months. Discussion This study will test the hypothesis that an intradialytic programme of exercise leads to a regression in left ventricular mass, an important non-traditional cardiovascular risk factor in end stage renal disease. For the first time this will be assessed using CMR. We will also evaluate the efficacy, feasibility and safety of an intradialytic exercise programme using a number of secondary end-points. We anticipate that a positive outcome will lead to both an increased patient uptake into established intradialytic programmes and the development of new programmes nationally and internationally. Trial registration number ISRCTN11299707 (registration date 5th March 2015). Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0294-7) contains supplementary material, which is available to authorized users.