Title: Understanding frailty, falls and the role of exercise in haemodialysis patients
Funder: Department of Health and Social Care

Abstract: Background Frailty is a a multidimensional syndrome of decreased physiological reserve which leads to an inability to respond appropriately to apparently minor health stressors. This clinically important phenomenon develops early and advances at an accelerated rate in haemodialysis (HD) patients. This is due to both high prevalence of traditional factors including sarcopenia and inflammation as well as factors unique to end-stage renal disease, including protein energy wasting, anaemia, abnormal vitamin D metabolism, cardiovascular disease and highly sedentary behaviour. Frailty in HD patients leads to increased mortality, hospitalisation, institutionalisation and reduced quality of life. Frail HD patients are also at a greatly increased risk of falling. They are approximately five times more likely to fall than healthy older adults and more likely to sustain a fracture as a result. Interventions to address frailty and falls in HD patients have received little research attention. Exercise interventions have shown promise in patients who are frail and fall without chronic kidney disease (CKD) but their ability to directly influence frailty and reduce the risk of falls in this population is unknown. There is also paucity of research exploring HD patients' experiences and beliefs about frailty and falls. This information is crucial to enhancing patient safety and care, raising awareness of the impact of falls in this population and the development and design of a targeted frailty and falls intervention. The aims of this study are to: establish the feasibility of a randomised controlled trial testing the ability of exercise to reduce frailty and falls risk in HD patients and; explore the lived experiences and beliefs of HD patients at risk of falls and their attitudes towards a specific intervention to address falls risk and frailty.Design This study is a distinct addition to an existing NIHR funded prospective, randomised cluster clinical trial (Trial ID number ISRCTN11299707, NIHR ref 17951). A mixed-method feasibility study will establish the viability of an clinical trial to definitively test the effects of exercise on frailty and falls risk in HD patients. Part one of this study will address the acceptability of the recruitment, randomisation and data collection methods and the rates of recruitment and retention. It will examine the appropriateness of the outcome measures and the intervention. Part two is a complementary and concurrent qualitative exploration of HD patients' individual experiences of frailty and falls and their attitudes towards a specific intervention targeting frailty and falls. Summary of the potential benefits In part one patients will benefit from improved physical functioning, quality of life, health and wellbeing as a result of being involved in the exercise programme. They may also benefit from a reduction in falls risk and increased safety as well as improved long-term outcomes associated with a slowing down in the frailty process. Improvements in these measures may also lead to reduced hospital admissions and length of stay, reducing the economic burden placed on the NHS. Part two will provide important information which will raise awareness of the impact of frailty and falls on HD patients, enhance their safety and make HD care more patientcentred. A knowledge gap within the HD literature will also begin to be addressed and will open further avenues for research which will improve outcomes for patients and will encourage dialysis providers to invest the time and resources required to implement and sustain exercise programmes for their patients. This work will also inform the design of a targeted intervention to reduce frailty and falls risk for pilot within five years.

Lay abstract: Why is this research needed?Frailty' describes a set of conditions which make patients vulnerable to sudden changes in health. Frailty begins earlier and progresses quicker in haemodialysis (HD) patients. This is due to both to a number of traditional factors (e.g. muscle wasting) very common in this population and to unique factors associated with end stage kidney disease (e.g. high levels of physical inactivity). Outcomes for frail HD patients are very poor - they are approximately five times more likely to fall than healthy older adults and more likely to break a bone as a result. Frailty and falls are also associated with reduced quality of life, loss of independence and increased use of health services. Interventions to address frailty and falls in HD patients have received little research attention. Exercise interventions benefit other patients who are frail or fall, but haven't been tested in HD patients. Studies into exercise training for HD patients are urgently needed, as well as a detailed understanding of patients' experiences of frailty and falls from their own perspectives. The results of this study will begin to explore if exercise is a suitable intervention to address frailty and falls risk and whether patients would be prepared to take part in a bigger study. It willidentify areas where the safety and clinical care of HD patients can be improved. Overall, patients will benefit from improved physical functioning, quality of life, potentially reduced falls risk and increased safety. The NHS may also benefit from a drop in hospital admissions and length of stay, overall saving money. This work will also be used to develop a specific intervention to address falls and frailty in HD patients for testing within five years. What do we aim to find out? To explore if dialysis patients are willing to take part in a study looking at whether exercise can improve frailty and falls risk, and whether a larger study would be possible. To understand haemodialysis patients' experiences, thoughts and feelings about falling . Study designPart one of this study will explore the feasibility of six months of exercise during dialysis to reduce frailty and falls risk. The study is linked to an ongoing trial of exercise funded by the NIHR, therefore patients who dialyse on certain shifts will randomly be assigned to exercise, whilst those on the other shifts will carry on with their usual dialysis sessions and not exercise.Patients who exercise will use a special static exercise bicycle during their dialysis treatments. All patients taking part will complete testing designed to measure frailty at the start, halfway through, and the end of the study. We will also look at patients' medical notes to see how many times they fell during the study and what the consequences of these were. In part two, we will carry out interviews with haemodialysis patients who fall to find out more about their experiences, thoughts and feelings. Afterwards we will ask them to keep a falls diary for one month. We will then interview them again to ask them more about their diaries and what they think about a specific frailty and falls intervention. Patient and public involvement Haemodialysis patients from our participant involvement group clearly told us that this is an important topic to them. They suggested we add the interviews and diaries into the study design and have helped to write this summary. We will work in partnership with our patient involvement group throughout the study. They will be actively involved in getting the approvals needed for the interviews, recruiting participants, analysing and publicising the results of the study. We will also write a report about our experiences of working together for other researchers and patient involvement groups. Who will the findings be communicated to and how? We will tell health professionals working with kidney patients, older patients and providing exercise programmes to patients with long-term conditionsabout our research finidings. The results will be presented at national and international conferences and published in a freely available, high impact medical journal. We will publicise the results through a number of high-profile national organisations including local NIHR Biomedical Research Units, the East Midlands CLAHRC and the NIHR funded National Centre for Sport and Exercise Medicine. We will inform kidney patients about our results through kidney charities, patient support groups and host a local celebration event' for all our dialysis patients. Finally we will use a range of social media to raise awareness of our research.

Research activity codes: 6.7 PHYSICAL
Health categories: INJURIES AND ACCIDENTS