Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile

Background Cardiovascular disease (CVD) 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 leukocyte 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 RPE of “somewhat hard”. Baseline characteristic were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leukocyte 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 (IL-6, CRP, TNF-α, intermediate and non-classical monocytes; all P<0.001). Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months the proportion of intermediate monocytes in the exercising patients reduced compared to non-exercisers (7.58±1.68 to 6.38±1.81% vs. 6.86±1.45 to 7.88±1.66%; P<0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P<0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions These findings suggest regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of CVD and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes

Implementing a theory-based intradialytic exercise programme in practice: a quality improvement project

Background Research evidence outlines the benefits of intradialytic exercise (IDE), yet implementation into practice has been slow, ostensibly due to lack of patient and staff engagement. The aim of this quality improvement project was to improve patient outcomes via the introduction of an IDE programme; evaluate patient uptake, sustainability and enhance the engagement of routine haemodialysis (HD) staff with the delivery of the IDE programme. Methods We developed and refined an IDE programme, including interventions designed to increase patient and staff engagement that were based upon the Theoretical Domains Framework, using a series of ‘Plan, Do, Study, Act’ cycles. The programme was introduced at two UK NHS HD units. Process measures included patient uptake, withdrawals, adherence and HD staff involvement. Outcomes measures were patient-reported functional capacity, anxiety, depression and symptomology. All measures were collected over 12 months. Results 95 patients enrolled in the IDE programme. 64 (75%) were still participating at three months, dropping to 41 (48%) at 12 months. Adherence was high (78%) at three months, dropping to 63% by 12 months. Provision of IDE by HD staff accounted for a mean of 2 (5%) sessions per three-month time point. Patients displayed significant improvements in functional ability (p=0.01), and reduction in depression (p=0.02) over 12 months, but effects seen were limited to those who completed the programme. Conclusions A theory-based IDE programme is feasible and leads to improvement in functional capacity and depression. Sustaining IDE over time is marred by high levels of patient withdrawal from the programme. Significant change at an organisational level is required to enhance sustainability by increasing HD staff engagement or access to exercise professional support

Native T1 mapping: inter-study, inter-observer and inter-center reproducibility in hemodialysis patients

Background Native T1 mapping is a cardiovascular magnetic resonance (CMR) technique that associates with markers of fibrosis and strain in hemodialysis patients. The reproducibility of T1 mapping in hemodialysis patients, prone to changes in fluid status, is unknown. Accurate quantification of myocardial fibrosis in this population has prognostic potential. Methods Using 3 Tesla CMR, we report the results of 1) the inter-study, inter-observer and intra-observer reproducibility of native T1 mapping in 10 hemodialysis patients; 2) inter-study reproducibility of left ventricular (LV) structure and function in 10 hemodialysis patients; 3) the agreement of native T1 map and native T1 phantom analyses between two centres in 20 hemodialysis patients; 4) the effect of changes in markers of fluid status on native T1 values in 10 hemodialysis patients. Results Inter-study, inter-observer and intra-observer variability of native T1 mapping were excellent with co-efficients of variation (CoV) of 0.7, 0.3 and 0.4% respectively. Inter-study CoV for LV structure and function were: LV mass = 1%; ejection fraction = 1.1%; LV end-diastolic volume = 5.2%; LV end-systolic volume = 5.6%. Inter-centre variability of analysis techniques were excellent with CoV for basal and mid-native T1 slices between 0.8–1.2%. Phantom analyses showed comparable native T1 times between centres, despite different scanners and acquisition sequences (centre 1: 1192.7 ± 7.5 ms, centre 2: 1205.5 ± 5 ms). For the 10 patients who underwent inter-study testing, change in body weight (Δweight) between scans correlated with change in LV end-diastolic volume (ΔLVEDV) (r = 0.682;P = 0.03) representing altered fluid status between scans. There were no correlations between change in native T1 between scans (ΔT1) and ΔLVEDV or Δweight (P > 0.6). Linear regression confirmed ΔT1 was unaffected by ΔLVEDV or Δweight (P > 0.59). Conclusions Myocardial native T1 is reproducible in HD patients and unaffected by changes in fluid status at the levels we observed. Native T1 mapping is a potential imaging biomarker for myocardial fibrosis in patients with end-stage renal disease

A 4-month programme of in-centre nocturnal haemodialysis was associated with improvements in patient outcomes

BACKGROUND: Extended periods of haemodialysis (HD) can improve patient outcomes. In-centre nocturnal haemodialysis (INHD) should be explored as a method of offering extended periods of HD to patients unsuitable for or unable to perform home therapy. METHODS: Ten self-selecting, prevalent HD patients started an INHD programme to assess feasibility and patient satisfaction. Quality-of-life (QOL) measures were evaluated at enrolment and after 4 months of INHD using the EQ-5D, the Hospital Anxiety and Depression Scale (HADS) and the SF-12 questionnaires. Demographic, biochemical and haematological data and data on dialysis adequacy were collected before starting INHD and after 4 months. RESULTS: Three of the 10 patients failed to complete the 2-week run-in period. Seven patients completed the 4-month programme, with mean dialysis time of 355 ± 43.92 min throughout the period. The EQ-5D visual analogue score improved from 48 ± 16.89 to 72 ± 13.2 (P = 0.003) and the HADS anxiety score decreased from 9 ± 5.83 to 3.57 ± 3.04 (P = 0.029). The urea reduction ratio improved from 71.57 ± 2.29% to 80.43 ± 3.101% (P < 0.001), with improvements in phosphate control, reducing to within the target range from 1.73 ± 0.6 to 1.2 ± 0.2 (P = 0.08). Ultrafiltration (UF) volumes increased during the study from 2000 ± 510 to 2606 ± 343 mL (P = 0.015); there was a significant reduction in mean UF rate adjusted for body weight from 6.47 ± 1.71 to 4.61 ± 1.59 mL/kg/h (P = 0.032). Sensitivity analyses confirmed the significance of these results. CONCLUSIONS: This single-centre study showed a 4-month programme of extended hours INHD is safe and associated with improvements in QOL measures, decreased UF rates and measures of dialysis adequacy. These data have been used to expand our service and inform the design of future randomized controlled trials to examine medical endpoints

Investigating the effects of 6 months extended duration, in-centre nocturnal versus conventional haemodialysis treatment: a non-randomised, controlled feasibility study.

INTRODUCTION: In-centre nocturnal haemodialysis (INHD) is an underutilised dialysis regimen that can potentially provide patients with better clinical outcomes due to extended treatment times. We have established an INHD programme within our clinical network, fulfilling a previously unmet patient need. This feasibility study aims to gather sufficient data on numerous outcome measures to inform the design of a multicentre randomised controlled trial that will establish the potential benefits of INHD and increase the availability of this service nationally and internationally. METHODS AND ANALYSIS: This will be a non-randomised controlled study. Prevalent patients on haemodialysis (HD) will electively change from a conventional in-centre HD regimen of 4 hours thrice weekly to a regimen of extended treatment times (5-8 hours) delivered in-centre overnight thrice weekly. After recruitment of the INHD cohort, a group of patients matched for age, gender and dialysis vintage will be selected from patients remaining on a conventional daytime dialysis programme. Outcome measures will include left ventricular mass as measured by MRI, physical performance measured by the short physical performance battery and physical activity measured by accelerometry. Additionally we will measure quality of life using validated questionnaires, nutritional status by bioimpedance spectroscopy and food diaries, and blood sampling for markers of cardiovascular disease, systemic inflammation. Suitable statistical tests shall be used to analyse the data. We will use omnibus tests to observe changes over the duration of the intervention and between groups. We will also look for associations between outcome measures that may warrant further investigation. These data will be used to inform the power calculation for future studies. ETHICS AND DISSEMINATION: A favourable opinion was granted by Northampton Research Ethics Committee (15/EM/0268). It is anticipated that results of this study will be presented at national and international meetings, with reports being published in journals during 2017. TRIAL REGISTRATION NUMBER: ISRCTN16672784

Regular exercise during haemodialysis promotes an anti-inflammatory leukocyte profile

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 < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P < 0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions: These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes

Novel cardiac nuclear magnetic resonance method for noninvasive assessment of myocardial fibrosis in hemodialysis patients.

Left ventricular hypertrophy and myocardial fibrosis frequently occur in patients with end-stage renal disease receiving hemodialysis therapy and are associated with poor prognosis. Native T1 mapping is a novel cardiac magnetic resonance imaging technique that measures native myocardial T1 relaxation, a surrogate of myocardial fibrosis. Here we compared global and segmental native myocardial T1 time and global longitudinal, circumferential and segmental strain, and cardiac function of 35 hemodialysis patients and 22 control individuals. The median native global T1 time was significantly higher in the hemodialysis than the control group (1270 vs. 1085 ms), with the septal regions of hemodialysis patients having significantly higher median T1 times than nonseptal regions (1293 vs. 1252 ms). The mean peak global circumferential strain and global longitudinal strain were both significantly reduced in hemodialysis patients compared with controls (-18.3 vs. -21.7 and -16.1 vs. -20.4, respectively). Systolic strain was also significantly reduced in the septum compared with the nonseptal myocardium in hemodialysis patients (-16.2 vs. -21.9) but not in control subjects. Global circumferential strain and longitudinal strain significantly correlated with global native T1 values (r = 0.41 and 0.55, respectively), and the septal native T1 significantly correlated with the septal systolic strain (r = 0.46). Thus, myocardial fibrosis may be assessed noninvasively with native T1 mapping; the interventricular septum appears to be particularly prone to the development of fibrosis in hemodialysis patients

A cost-effective analysis of the CYCLE-HD randomized controlled trial

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

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

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

Native T1 mapping: inter-study, inter-observer and inter-center reproducibility in hemodialysis patients

BACKGROUND: Native T1 mapping is a cardiovascular magnetic resonance (CMR) technique that associates with markers of fibrosis and strain in hemodialysis patients. The reproducibility of T1 mapping in hemodialysis patients, prone to changes in fluid status, is unknown. Accurate quantification of myocardial fibrosis in this population has prognostic potential. METHODS: Using 3 Tesla CMR, we report the results of 1) the inter-study, inter-observer and intra-observer reproducibility of native T1 mapping in 10 hemodialysis patients; 2) inter-study reproducibility of left ventricular (LV) structure and function in 10 hemodialysis patients; 3) the agreement of native T1 map and native T1 phantom analyses between two centres in 20 hemodialysis patients; 4) the effect of changes in markers of fluid status on native T1 values in 10 hemodialysis patients. RESULTS: Inter-study, inter-observer and intra-observer variability of native T1 mapping were excellent with co-efficients of variation (CoV) of 0.7, 0.3 and 0.4% respectively. Inter-study CoV for LV structure and function were: LV mass = 1%; ejection fraction = 1.1%; LV end-diastolic volume = 5.2%; LV end-systolic volume = 5.6%. Inter-centre variability of analysis techniques were excellent with CoV for basal and mid-native T1 slices between 0.8-1.2%. Phantom analyses showed comparable native T1 times between centres, despite different scanners and acquisition sequences (centre 1: 1192.7 ± 7.5 ms, centre 2: 1205.5 ± 5 ms). For the 10 patients who underwent inter-study testing, change in body weight (Δweight) between scans correlated with change in LV end-diastolic volume (ΔLVEDV) (r = 0.682;P = 0.03) representing altered fluid status between scans. There were no correlations between change in native T1 between scans (ΔT1) and ΔLVEDV or Δweight (P > 0.6). Linear regression confirmed ΔT1 was unaffected by ΔLVEDV or Δweight (P > 0.59). CONCLUSIONS: Myocardial native T1 is reproducible in HD patients and unaffected by changes in fluid status at the levels we observed. Native T1 mapping is a potential imaging biomarker for myocardial fibrosis in patients with end-stage renal disease