Combination of Medium Cut-off Dialyzer Membrane and Diet Modification to Alleviate Residual Uremic Syndrome of Dialysis Patients

Combination of Medium Cut-off Dialyzer Membrane and Diet Modification to Alleviate Residual Uremic Syndrome of Dialysis Patients

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);