Title: Individualised fluid management in haemodialysis: combining bioimpedance and absolute blood volume measurements for improved clinical effectiveness and patient experiences
Funder: Health Education England

Abstract: Background: Bioimpedance is gaining acceptance as an objective tool for fluid management in haemodialysis (HD). Observational studies have shown that patients may benefit from individualised fluid management; however there is a need for additional diagnostic tests alongside bioimpedance to guide individualisation. In particular, measurement of absolute blood volume (ABV) will give a more specific indicator of cardiovascular risk factors than whole-body fluid volumes measured by bioimpedance.Aims: The aim of this study is to facilitate individualisation of fluid management strategies in HD to minimise the risks associated with both fluid overload and fluid depletion.Objectives: Primary objective: To demonstrate that the relationship between measurements of fluid status using the body composition monitor (BCM) and ABV measurements are mediated by easily characterised clinical characteristics, including body mass index (BMI), lean tissue index (LTI) and the presence of lower limb oedema. Secondary objective: To compare the criterion analysis of ABV measurements with a simplified technique to assess whether the simplified approach can provide reliable results suitable for use in routine practice.Population: A number of distinct cohorts will need to be recruited. A reference group will be compared against three patient groups who are clinically challenging with respect to fluid management. Cohort 1-Reference group: Patients who have normal fluid status, low intradialytic fluid gains and normal fluid volumes. Cohort 2-High BMI group: Patients with high BMI who routinely finish dialysis with significant fluid depletion, as defined by BCM, without intradialytic symptoms. Cohort 3-Low LTI group: Patients who have a low LTI due to sarcopenia or malnutrition or a combination of both and who routinely finish dialysis with a degree of excess fluid as defined by BCM, with or without the presence of EVLW. Cohort 4-Localised oedema group: Patients who have localised lower limb oedema. Methods: By introducing a bolus of dialysate into the blood lines and tracking the change in relative blood volume (RBV), the distribution volume (ABV) can be calculated. This will be done using the criterion analysis method (ABVcrit) as well as a simplified technique (ABVsimp) that requires less time and no technical expertise. Measurements will be made within the last 20 minutes of HD, normalised to lean tissue mass (LTM) and corrected for RBV changes to give post-dialysis ABV. Fluid status will be assessed using BCM-measured overhydration (OH), which also measures LTM and LTI. Extravascular lung water will be measured using lung ultrasound pre- and post-dialysis.Analysis: Normalised post-dialysis ABVcrit will be compared between the reference group and each of the other groups to assess the effect of BMI, LTI and localised fluid on the relationship between BCM-measured OH and ABV. Comparisons will be based on two sample t-tests with Bonferroni corrections. All ABV measurements will be included in Bland-Altman analysis comparing ABVcrit to ABVsimp to investigate the acceptability of the simpler technique.Sample size: Recruiting 40 patients into each cohort would allow differences of about 7 ml/kg to be observed with 5% type I error and 80% power. This has previously reported as being the difference between stable and symptom-prone patients.Research impact: The findings of this research will feed directly into routine NHS care based on a regular training programme for local practitioners and to other NHS units. This will be supplemented through a strong dissemination stratedy with collaborative partners in the UK and internationally.

Lay abstract: Around 60,000 patients in the UK are being treated for severe kidney failure at a cost to the NHS of 1% of its budget. The most common treatment is haemodialysis (HD). An important part of HD is removing extra fluid from the body which the kidneys normally remove in urine. Deciding how much fluid to remove is not easy. It is normally based on clinical signs, such as blood pressure or tissue swollen with fluid. However, this approach includes a certain amount of guess-work and there is a need for better tests to help guide these decisions.Bioimpedance tests are a common way of measuring body composition. They involve passing a small electric current through tissue using stickers on the skin. The impedance (the opposition to the flow of current) is closely linked to the amount of water in the body and it can be used to estimate fluid status. The test is portable, cheap, simple to use, painless and harmless. One bioimpedance device, the Body Composition Monitor (BCM), has been designed particularly for kidney patients. There is growing evidence that using the BCM to help fluid management can improve patient symptoms and survival.One problem with the BCM is that it does not take into account some clinical differences between patients. My PhD developed the basics of using the BCM in a more individualised way. This approach tries to consider some important factors that can affect how fluid builds up in patients and how patients tolerate fluid removal. These include: how much urine they are passing body mass index (BMI) age appetite and nutritional state localised fluid and swelling There is a need for further work to develop this approach and make use of other measures that can help to guide treatment for an individual patient. One of the biggest effects is likely to be related to differences in the amount of fluid in the blood (the blood volume) which the BCM cannot measure. The fluid that is in the blood has the biggest effect on patients' health but until now there has not been a simple way of measuring it.The aim of this study is to see whether blood volume measurements can help to make fluid management more individualised. This would reduce the impact of dialysis on patients' health and improve patients' experience of the treatment. Objective 1: To demonstrate whether the addition of blood volume measurements can help to tailor fluid management to HD patients' individual needs. In particular we will look at how body size, nutritional state, age and localised fluid can affect patients' blood volume.Objective 2: To see if there is a simple way of making blood volume measurements with no need for expertise or extra equipment. This would mean that the measurements could be available to all HD patients. We hope to recruit 40 patients to four different groups. Patients who: still pass urine and need little fluid removed during dialysis have high BMI and finish dialysis dehydrated do not have much lean tissue and finish dialysis with small amounts of excess fluid have localised build-up of fluid, such as in the ankles The patients will have measurements of BCM and blood volume, as well as tests for fluid in the lungs. The results of the measurements will be compared between groups to help us understand how decisions about fluid management can be tailored to keep blood volume at the optimal level.Kidney patients from a number of renal units have helped develop the study in a way which they feel will be acceptable to HD patients. This group have agreed to support the project as a patient advisory panel. The panel will be led by David Coyle, a kidney patient with significant experience of HD and patient involvement within the NHS. The patient advisory group will help us inform the patient community of the results of the project and our national and international partners will help inform the wider kidney community. If successful, this work could feed directly into patient care, improving patient experience during dialysis and patients' long term well-being.A bespke supervision and training programme is also proposed to develop my clinical skills alongside the research, focussing on the common themes of medical device risk management and device developement within the NHS. This will aloow me to come out of the programme with an international reputation for research and as a highly skilled Clinical Engineer able to facilitate and manage medical device use in research and clinical practice.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: RENAL AND UROGENITAL