Title: Micronutrient loss during renal replacement therapy in acute kidney injury
Funder: Department of Health (England)

Abstract: Acute Kidney Injury (AKI) is common (affecting approximately 20% of patients admitted to hospital with acute illness), serious (with mortality rates of over 60% for patients with AKI requiring renal replacement therapy [RRT] in the intensive care unit) and expensive (costing the NHS an estimated £620 million per year). Malnutrition is common in serious acute illness and also in AKI, but there has been very little research directed at nutrition in AKI. In severe cases of AKI, supportive care with RRT is required, until kidney function recovers sufficiently. There are various types of RRT used clinically, varying in duration and frequency of treatment, and also in the physical mechanism of solute removal (diffusion, convection or a combination of the two). Intermittent haemodialysis (IHD) is typically used for 2-4 hours daily or on alternate days and uses diffusion for solute removal. Continuous veno-venous haemofiltration (CVVH) is used continuously, usually in the intensive care unit (ICU) and is based on solute removal by convection. Sustained low efficiency diafiltration (SLEDf) is used for 8-12 hours daily or alternate days, and uses a combination of diffusion and convection. The purpose of any type of RRT is to remove toxic molecules, including metabolic waste products, from the blood stream, as well as to maintain fluid balance. In addition to removing unwanted molecules, it is inevitable, because of the non-selective mechanisms involved, that useful small water-soluble molecules will be removed to some extent. These are likely to include micronutrients such as trace elements (selenium, copper, iron, zinc, manganese etc), amino acids and water soluble vitamins (thiamine, B6, folic acid, vitamin C etc). Patients with acute illness are known to be at high risk of malnutrition, as are patients with AKI. The extent of malnutrition in patients with AKI is not known. The extent to which micronutrients are lost during RRT is not known, nor is it known whether certain types of RRT are more likely to lead to micronutrient loss than others. These are clearly important questions when the patients requiring these life-saving therapies are likely to be malnourished even before commencing RRT. This study therefore aims to quantify losses of specific micronutrients, to assess whether the amounts lost during RRT are likely to be clinically significant. The study will also compare micronutrient losses between 3 different types of RRT, chosen because of their widespread use in renal units and ICUs, but also because they vary in duration of treatment (intermittent to continuous) and in solute clearance mechanism (diffusion versus convection). Adult patients with AKI requiring RRT admitted to the renal unit or general ICU at Nottingham University Hospitals will be recruited over a period of approximately 20 months. The mode of RRT (IHD, SLEDf or CVVH) will be determined on clinical grounds by the patient's consultant, with recruitment to the study having no influence. Blood and dialysate (or 'effluent' from CVVH) samples will be taken at regular intervals through and one hour after RRT, for the first two RRT sessions (where a second session is required). Intermittent urine samples will also be collected where the patient is not anuric. Samples will be analysed to quantify total losses of individual micronutrients caused by RRT and will be corrected for dialysis dose. Changes in blood concentration will be assessed, as will micronutrient losses caused by adsorption to the RRT filter/dialyser. The study will provide valuable information on which micronutrients are lost in potentially significant quantities, and whether certain RRT modalities are more likely to cause micronutrient loss. It will provide information for design of specific nutritional supplements which could be tested in subsequent interventional studies.


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