Title: PlasmaLyte Usage and assessment of kidney Transplant Outcomes in children: the PLUTO trial. A randomised controlled open-label trial comparing PlasmaLyte to standard intravenous fluid in paediatric kidney transplant recipients.
Funder: Department of Health and Social Care

Abstract: Research question In children who have received a kidney transplant, does PlasmaLyte-148 intravenous fluid reduce plasma electrolyte imbalance compared to standard intravenous fluid therapy? Background Acute hyponatraemia is documented to disrupt brain function in children following kidney transplant resulting in unpleasant symptoms including nausea and vomiting, headaches, and reduced conscious level(1, 2). Severe effects include encephalopathy, cerebral oedema, seizures and death(2, 3). Hyponatraemia is common following kidney transplant documented in 59% of children, with seizures in 8% of patients treated with standard fluid therapy(2, 4). Currently, hypotonic intravenous fluid is used in the majority of UK paediatric kidney transplant centres. National guidance recommending isotonic fluid has not been adopted because of a view that the period following kidney transplantation differs from other situations in terms of the large volume of fluid administered. Aim and Objectives The PLUTO trial will evaluate whether PlasmaLyte-148 [intervention] will reduce the incidence of dangerous electrolyte abnormalities [outcome] in children following kidney transplantation [population] compared to current standard fluid therapy [comparator]. Objectives: to evaluate the clinical effect of PlasmaLyte-148 on: Hyponatraemia Symptoms including nausea/vomiting, headache and seizures Fluid overload Time to discharge from hospital Transplant kidney function Hyperkalaemia, acidosis, hyperglycaemia and hypomagnesaemia Methods The PLUTO trial is a multi-centre open label randomised controlled trial comparing electrolyte abnormalities in children following kidney transplantation with the use of PlasmaLyte-148 compared to standard intravenous fluid. Children under 18 years of age receiving a kidney transplant in a participating paediatric transplant centre will be eligible. A total of 144 participants will be randomised 1:1 to intervention or control groups. The control group will receive standard clinical care (0.45% sodium chloride 5% glucose in 8 centres, and a combination of 0.9% sodium chloride and 5% glucose in 2 centres). The intervention group will receive PlasmaLyte-148 as first line intravenous fluid intra-operatively and post-operatively. The primary outcome will be the proportion of patients who experience hyponatraemia ([Na] Timelines for delivery Study duration 36 months (3 months set-up, 30 months recruitment and follow-up and 3 months close-out). Anticipated Impact and Dissemination The PLUTO trial will determine whether dangerous plasma electrolyte imbalance will be different with the use of PlasmaLyte-148 compared to standard intravenous fluid in children following kidney transplant. A positive result would provide high quality evidence to change current practice. This could reduce the risk of hyponatraemic encephalopathy and death in 130 children who receive kidney transplants each year in UK, and prevent hyponatraemic seizures in 10 children each year. We will disseminate results via the National Health Service Blood and Transplant (NHSBT) Paediatric Kidney Advisory Group, and internationally via conference presentation and journal publication.

Lay abstract: Kidney transplantation transforms the lives of children with severe kidney disease. It allows many to return to a life without very frequent hospital visits or dialysis treatment. But the transplant itself is a big operation. In the first few days after kidney transplant, many children develop dangerous changes in the amount of salt and water in the bloodstream. This is because doctors give very large volumes of artificial fluids into the veins to keep the new kidney working. If the main salt in the blood (sodium) falls too far, serious problems including brain damage and even death can occur. Because of this, we take blood samples from each child every 2-4 hours for the first day after the transplant operation to check sodium levels and change them if necessary. This research aims to compare the standard fluid used after the transplant operation with an alternative that may reduce dangerous changes in salt (sodium) levels and help the transplant kidney to work better. The new fluid is called PlasmaLyte. It matches the normal composition of blood more closely than standard fluid. PlasmaLyte is already used in other sick children, including those on intensive care units. Although there are good reasons to believe that PlasmaLyte may be a safer choice of fluid for children after kidney transplant, there is no evidence comparing PlasmaLyte with standard fluid for children. We plan to work out which of the two fluids is better by looking at children s kidney transplants in the UK, half using the standard fluid and half using the new fluid. The choice of fluid will be made randomly by a computer. We will compare the number of children in each group who have low blood salt levels, and their transplant kidney function. No additional blood samples will be required. Children who participate in the study will continue to have all the usual care that they would otherwise receive. All of the UK children s kidney transplant centres will be involved. Feedback from families of children awaiting kidney transplantation has helped us design this study. Families felt that this research is important, because its aim is to improve safety and kidney transplant function. In response to two children s concerns, research participants will not undergo any additional blood samples (only those needed for their routine clinical care). This will be highlighted in the patient information documents. As suggested by a parent, we will make it clear that PlasmaLyte is not an experimental treatment, but a licenced fluid given to other groups of patients. This study has the potential to change clinical practice and importantly improve the treatment and outcomes of children receiving kidney transplants in the UK.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL