Title: Study To Investigate The Change in Hypotensive Episodes during Dialysis (STITCHED)
Funder: Medical Research Council

Abstract: Aims of the research _x000D_ This study will investigate whether patients with chronic kidney disease treated by haemodiafiltration (HDF) a modification of haemodialysis (HD) reduces structural and functional damage to the brain in kidney dialysis patients by reducing episodes of low blood pressure during dialysis and blood pressure variability. This will provide important new information on the effect of low blood pressure during dialysis and blood pressure variability and outcomes in dialysis patients which will influence clinical practice, as currently there are no UK clinical guidelines for blood pressure control in dialysis patients. This study will provide information about the differences in dialysis centre practices and the effects of blood pressure variability and changes in brain structure and function, which will influence future clinical practice_x000D_ _x000D_ Background to the research _x000D_ Strokes costs UK society £8.9 billion/year, with treatment costing 5% of total UK NHS spending. Patients with kidney failure treated by haemodialysis (HD) are at much greater risk of stroke, but also suffer greater severity of disability, with fewer recovering to be discharged home. Small bleeds into the brain usually cause no symptoms, but these microbleeds are much more common in HD patients, and elderly nursing home patients rapidly become more frail and dependent after starting HD. In the general population, there is a strong link between high blood pressure (hypertension), stiffness of the arteries and stroke risk. Hypertension is common in HD patients, but hypertension is not a significant risk factor for stroke. Whereas the normal kidney works continuously, kidney dialysis patients are treated only three times a week, so they gain fluid from one HD session to the next, and this fluid overload then needs to be removed during the next HD session to restore the patient back to normal. Fluid removal may lead to low blood pressure (hypotension) during the HD session, termed intradialytic hypotension (IDH), and IDH is the commonest complication of HD treatments. The change in blood pressure from high pre-HD to low during HD is associated with increased patient mortality, and damage to the brain, leading to multi-infarct dementia. _x000D_ _x000D_ Design and methods used _x000D_ We will recruit patients from The UK High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT). A research nurse will collect the initial clinical information. All follow-up dialysis data is routinely collected by the UK Renal Registry. Patients will have an assessment of cognitive function, measurement of blood pressure between dialysis sessions and fluid overload, and 3 additional blood tests at study entry, 12 months and at 24 months, and 2 echocardiograms at start and study end. Potential or actual barriers to recruitment will be identified and strategies to optimise recruitment developed._x000D_ _x000D_ Patient and public involvement_x000D_ The main H4RT study was selected by patients on the UK Renal Registry’s Patient Council and a local kidney patient association. Patients wanted the study to focus on survival and life-threatening hospital admissions. Patients at local kidney patient associations were contacted as to investigations to be used for this sub-study and the frequency of investigations._x000D_ _x000D_ Dissemination_x000D_ Findings from the research will be made public through patient newsletters, social media and patient meetings,and be written up in research journals and presented at conferences.

Lay abstract: The treatment of, and productivity loss arising from stroke has been estimated in total societal costs at £8.9 billion/year, with treatment costs of stroke accounting for ˜5% of total UK NHS spending [1]. Haemodialysis (HD) patients are not only at greater risk of stroke (42-50/1,000 patient years) [2], and mortality from stroke, but also suffer greater severity of disability, with fewer HD patients recovering to be discharged home [3]. Brain microbleeds are more prevalent in asymptomatic patients with chronic kidney disease [4], and elderly nursing home patients starting HD are reported to rapidly become more frail and dependent [5]. There are more than 30,000 patients treated by HD in the UK, and proportionally the greatest increase in the UK dialysis population is in elderly patients. These patients are at increased risk of stroke and sub-clinical cerebrovascular disease_x000D_ In the general population, there is a linear association between systolic blood pressure (SBP) and stroke risk. Whereas, although hypertension is common amongst HD patients, hypertension is not a significant risk factor for stroke in the HD population [2]. During HD fluid gains from one HD session to the next is removed to restore the patient to a normohydrated state. Fluid removal may lead to hypotension during the HD session, the commonest complication of outpatient HD treatments. The change in BP, from high SBP pre-HD to low SBP during HD is reported to be associated with increased patient mortality [6], and increased multi-infarct dementia [7]. Advances in dialysis have introduced convective clearance in addition to the diffusive clearance of standard HD. Haemodiafiltration (HDF) treatments can now permit the exchange large volumes of fluid with patients during a HDF session. A previous trial of high volume HDF reported improved survival compared to standard HD, and a reduction in both intra-dialytic hypotension (IDH) and stroke [8]. The UK NIHR sponsored H4RT study will investigate the effect of high volume HDF compared to standard HD on patient survival, hospital admissions and patient reported symptoms. To determine the mechanisms as to why high volume HDF improves dialysis patient survival and stroke, we will primarily determine episodes of IDH. Using previously reported IDH rates [8], then for a clinically significant 30% reduction in IDH with HDF, for 90% power at the 5% significance level, we would require 138 patients in each arm. To allow for patient drop out we would need to recruit 345 patients which could be achieved by 10 centres recruiting 3 patients/month for 12 months, and patients followed for 24 months. Secondly, we propose measuring BP variability using ambulatory BP monitoring and arterial stiffness by pulse wave velocity, and correlating these with changes in echocardiographic cardiac dimensions and functional assessments of patient cognitive function. We will compare middle sized uraemic toxin removal between the two modes of dialysis by measuring ß2 microglobulin clearance. This study will provide important new information on the effect of IDH and BP variability and outcomes in dialysis patients which will influence clinical practice, as currently there are no UK clinical guidelines for BP control in dialysis patients. In addition, this study will provide information about the differences in dialysis centre practices and IDH and changes in brain structure and function, which will influence future clinical practice.

Research activity codes: 5.7 PHYSICAL
Health categories: RENAL AND UROGENITAL