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.

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);

Plan to share IPD that underline results published in the manuscripts reporting study results.

From the time of publication of associated manuscripts for 10 years.

Available on demand from the investigators.