the effect of combining medium cut off dialysis membrane and diet modification on reducing of inflammation response

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

Summary: the investigators purpose is to research the impact of the simultaneous use of a new dialysis membrane with higher permeability for medium and protein bound uraemic toxins (medium cut-off dialysis membrane theranova®) combined with diet modification to reduce the level of inflammation in chronic dialysis patients. the investigators hypothesize that the use of a medium-cut off dialysis membrane and dietary modification work synergistically and cause a significant and clinically meaningful reduction in inflammation levels compared to on-line hemodiafiltration with a high-flux dialysis membrane.

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 interleukin-6. secondary outcome is the serum concentration of interleukin-10, serum amyloid a, high-sensitivity c-reactive protein, total leukocyte count and plasma concentration of bacterial 16s rdna. 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 hospital 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 * acute febrile inless 4 weeks prior to study inclusion * active chronic inflammation (e.g., an active autoimmune disease or an open wound), chronic ongoing infection or cancer * new cardiovascular or cerebrovascular event 4 weeks prior to study inclusion * clinically malnourishet patient and/or bmi below 19 kg/m2 and/or loss of more the 5% of body mass in the 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 after 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)