Title: Evaluation of the Effect of Cooled HaEmodialysis on Cognitive Function in Patients suffering with End-Stage KidnEy Disease: Feasibility Study (E-CHECKED)
Funder: Department of Health and Social Care

Abstract: In the UK, 26000 patients receive haemodialysis (HD) for End-Stage Kidney Disease (ESKD) three times a week at a yearly cost of &pound;636 million. ESKD is associated with a graded increase in prevalence of cognitive impairment13,14 and a decrease in brain perfusion independent from vascular risk factors15. At least 30-70% of dialysis patients6 suffer from moderate cognitive impairment6,17, which is independently associated with higher rates of depression, mortality6,18 and reduced quality of life4-7. Unsurprisingly, dialysis patients value quality-of-life more than life expectancy8,9. To date, no interventions are proven to slow cognitive decline or improve quality of life in this group of patients10-12,19. The use of cooler dialysate (34-35&deg;C) to prevent intradialytic hypotension was first described in 198133. However, it is greatly underused due to perceptions about thermal symptoms34,35. A recent RfPB funded pilot study in 38 patients, showed cooled dialysis fluid prevented progression of ischemic brain white matter changes after one year38,39. However, the effects of cooler dialysate on cognitive impairment, quality-of-life and illness burden are not known. How well cooler dialysis fluid is tolerated is also not sufficiently reported. Currently in the UK, temperatures between 36&deg;C and 37&deg;C are used, but international clinical guidelines recommend a minimum temperature for the dialysate of 35&deg;C43,44 mainly for cardiovascular stability. There have been recent calls for larger trials using this cheap and universally applicable intervention that focused on these patient important outcomes34,35. Aims: To test the feasibility of the investigation of lower temperatures of dialysis fluid to prevent the decline in cognitive function and improve quality-of-life in haemodialysis patients. This would inform the development of a definitive, fully powered randomized controlled clinical trial within two years. Target Population Patients receiving haemodialysis three-times weekly for End-Stage Kidney Disease (ESKD) for at least 3 months in specialized centres. Interventions 1. Intervention group use cooled dialysate at temperature of 35&deg;C for 12 months 2. Control group use standard dialysate at 36.5&deg;C for 12 months Study design The study is a multicentre, prospective, randomised, double-blinded, controlled feasibility trial with a 1:1 allocation ratio. Ninety patients from three centres will be recruited after three months from starting HD. Patients who are 50 years and above receiving haemodialysis for ESKD for at least 3 months and have mental capacity to consent for the study will be included. We will exclude patients with established diagnosis of dementia, suffering from psychiatric or physical conditions or on any treatment that might affect their cognitive performance. Patients who are participating in another investigational medicinal product study or unlikely to be able to maintain their participation in the study for 12 months, will be excluded. The relevant outcomes are trial feasibility and mean and variance estimates for Cogstate composite index in the control and possibly intervention arms. Overall feasibility of the trial will be assessed based on recruitment rates and strategy with respect to inclusion and exclusion rates as well as consent rates, adherence to treatment protocol, rate of recruitment after 6 months, withdrawal rates, missing data and costs of running the study using mixed methods. Cognitive function and quality of life indicators and carers burden will be measured at baseline, 6 months and 12 months by a different blinded independent rater. The success of our study will prepare for a definitive clinical trial that would offer a new clinical intervention at no added cost, with the benefit of lessening the effect of HD on patients cognitive function and improving quality of life, which would lead to reduction in disease burden. This study will validate the use of novel computerized neuropsychological battery (CogStat) and MoCA (English version) for the use of HD patients.

Lay abstract: Patients with kidneys that do not work properly need a kidney machine to remove excess fluid and waste producst from the body; a process called haemodialysis. In the UK, 26000 patients receive haemodialysis three times weekly for 4 hours with yearly costs of &pound;636 million. The numbers needing haemodialysis are rising, particularly in older people. Average survival in UK haemodialysis patients in five years is worse than for most cancers. Haemodialysis is a huge burden for patients and their family or carers. Most patients endure unpleasant symptoms and poor quality-of-life with high rates of depression, thinking difficulties and memory problems (known as cognitive impairment). This reduces the ability to cope with taking many medicines, eating and drinking restrictions. Dialysis patients value quality-of-life over life expectancy, but no treatments have been shown to help. During haemodialysis, fluids are removed that cause sudden drops in blood pressure, with dizziness and muscle cramps. These drops in blood pressure damage the heart and brain and may cause the high levels of cognitive impairment in haemodialysis patients (30-70%). Several, small, short-term studies suggest using cooler fluid during haemodialysis reduces blood pressure drops. A recent small trial showed cooler dialysis fluid might prevent brain injury by reducing these drops in blood pressure. Few studies report how well tolerated cooler dialysis fluid is, but effects on cognitive impairment and quality-of-life are not known. As all patients can use cooler dialysis fluid at no added cost, a trial to test the health benefits to prevent cognitive impairment and preserve quality-of-life is urgently needed. This feasibility study will randomly give 90 haemodialysis patients either standard or cooled fluid for one year. This study is a useful way to let us test the possible issues with how to run the next study that will be big enough to determine this.

Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL;NEUROLOGICAL