combination of medium cut-off dialyzer membrane and diet modification to alleviate residual uremic syndrome of dialysis patients

Conditions: End Stage Renal Disease; Haemodialysis; Diet, Healthy

Summary: the study will compare achieved levels of protein-bound uremic toxins with dialysis using a medium cut-off membrane compared to the treatment by online haemodiafiltration with a high-flux dialysis membrane. in the second phase of the study dietary fiber and short-chain fatty acid intake will be increased to verify a possible additional reduction in the levels of protein bound uremic toxins.

the investigators will carry out a prospective interventional randomised study to compare achieved serum concentrations of selected protein bound uremic toxins by dialysis with a medium cut-off membrane (theranova, baxter ag, usa) and online hemodiafiltration with a standard "high-flux" dialysis membrane. in the second phase, both dialysis purification methods will be supplemented by a change in the diet with increase of the daily intake of dietary fiber to 30g and addition of a short-chain fatty acid propionate in the dose of 1 g daily. the main outcome of the study is the serum concentration of p-cresol sulphate. secondary outcome is the serum concentration of indoxyl-sulphate and trimethylamine-n-oxide (tmao). serum albumin concentration and lean body weight of patients represent safety outcomes for this study. this investigator-initiated research project has been entirely planned and will be conducted by the clinical researchers in a tertiary university medical center ljubljana. the study will include 50 chronic prevalent stable dialysis patients in the following periods: * 2 weeks of wash-in period with standard bicarbonate haemodialysis and standard high-flux dialysis membrane, * then the patients will be randomized in a 1:1 ratio to either one of the two study arms: * (interventional study arm) 4 weeks of dialysis with medium cut-off (theranova) membrane (first phase), then dialysis for 4 weeks with the same membrane and increased fiber intake (second phase), * (control study arm) 4 weeks of dialysis with a high-flux membrane using on-line haemodiafiltration (first phase) and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake (second phase), * finally, all patients will undergo a 4 week wash-out period with a standard bicarbonate haemodialysis using standard high-flux dialysis membrane identical to wash-in period. measurement of the study end-points will be carried out at the end of 2-week wash-in period, each 4-week period and at the end of 4 week wash-out period.

Eligibility criteria:
inclusion criteria: * patient on chronic hemodialysis or hemodiafiltration for at least 12 weeks, * age 18 years old or more, * a functioning arteriovenous fistula or graft as a permanent dialysis vascular access, * being able to give an informed consent to participate in the survey; exclusion criteria: * planned kidney transplantation, transition to peritoneal dialysis or to another dialysis center within 12 weeks of the start of the study, * active chronic inflammation (e.g., an active autoimmune disease or an open wound), chronic ongoing infection or cancer in last 4 weeks, * acute febrile illness in last 4 weeks, * new cardiovascular or neurovascular event in last 4 weeks, * a need for hospitalization in the last 4 weeks, * clinically evident malnutrition and/or body mass index of 19 kg/m2 and/or loss of body weight for 5% in last 3 months, * immunosuppressive treatment, * expected survival of less than 1 year, * pregnancy or breast-feeding, * indication for dietary supplements to increase calorie and / or protein intake, * specific indication for carrying out hemodiafiltration instead of hemodialysis as per attending physician, * serum albumin concentration \<32 g/l at screening to enter the study, * inability to follow the study diet or test procedures, * rapid reduction of residual renal function in the period prior to entry into the study, * intolerant of on-line haemodiafiltration (infusion intolerance);

Keywords: medium cut-off dialysis membrane p-cresol sulphate indoxyl-sulphate trimethylamine-n-oxide (tmao) hemodiafiltration uremic toxins dietary fibre end stage renal disease