The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

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.

The cardiovascular determinants of physical function in patients with end-stage kidney disease on haemodialysis.

Patients with end-stage kidney disease (ESKD) are often sedentary and decreased functional capacity associates with mortality. The relationship between cardiovascular disease (CVD) and physical function has not been fully explored. Understanding the relationships between prognostically relevant measures of CVD and physical function may offer insight into how exercise interventions might target specific elements of CVD. 130 patients on haemodialysis (mean age 57 ± 15 years, 73% male, dialysis vintage 1.3 years (0.5, 3.4), recruited to the CYCLE-HD trial (ISRCTN11299707), underwent cardiovascular phenotyping with cardiac MRI (left ventricular (LV) structure and function, pulse wave velocity (PWV) and native T1 mapping) and cardiac biomarker assessment. Participants completed the incremental shuttle walk test (ISWT) and sit-to-stand 60 (STS60) as field-tests of physical function. Linear regression models identified CV determinants of physical function measures, adjusted for age, gender, BMI, diabetes, ethnicity and systolic blood pressure. Troponin I, PWV and global native T1 were univariate determinants of ISWT and STS60 performance. NT pro-BNP was a univariate determinant of ISWT performance. In multivariate models, NT pro-BNP and global native T1 were independent determinants of ISWT and STS60 performance. LV ejection fraction was an independent determinant of ISWT distance. However, age and diabetes had the strongest relationships with physical function. In conclusion, NT pro-BNP, global native T1 and LV ejection fraction were independent CV determinants of physical function. However, age and diabetes had the greatest independent influence. Targeting diabetic care may ameliorate deconditioning in these patients and a multimorbidity approach should be considered when developing exercise interventions.

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.