End Stage Renal Disease, Haemodialysis, Diet, Healthy, Chronic Inflammation
Conditions
Brief 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.
Detailed description
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.
Interventions
Medium cut-off dialysis (MCO) membrane is a dialysis membrane with a higher molecular weight retention onset and similar cut-off as standard high-flux dialysis membranes. It is capable of providing increased clearance of medium sized uremic toxins and some plasma proteins (cytokines, inflammatory mediators).
DIETARY_SUPPLEMENTDietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)
Dietary fiber (Psyllium 69% and Inulin 30% mixture) added to the meals in the dose of 5g BID for 4 weeks in the second phase of the study.
DIETARY_SUPPLEMENTSodium propionate
Sodium propionate (a short-chain fatty acid) added to the meals in the dose of 500 mg BID in the second phase in the study.
Sponsors
University of Ljubljana
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, randomized, interventional, two parallel arm study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum concentration of inflammatory mediator interleukin-6 (IL-6). | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of serum total interleukin-6 concentration will be taken from the arterial line before the start of midweek hemodialysis procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum concentration of inflammatory mediator High-sensitivity C-reactive protein (hs-CRP). | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of serum total hs-CRP concentration will be taken from the arterial line before the start of midweek hemodialysis procedure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum leukocyte count. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of total serum leukocyte count will be taken from the arterial line before the start of midweek hemodialysis procedure. |
| Plasma concentration of bacterial 16s rDNA. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of plasma concentration of bacterial 16s rDNA will be taken from the arterial line before the start of midweek hemodialysis procedure. |
| Serum albumin concentration. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of serum albumin concentration will be taken from the arterial line before the start of midweek hemodialysis procedure. |
| Serum concentration of inflammatory mediator interleukin-10 (IL-10). | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of serum total interleukin-10 concentration will be taken from the arterial line before the start of midweek hemodialysis procedure. |
| Time to finish 10 repetition sit to stand test. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | This validated test measures lower limb strength. Participants are required to stand up and sit down 10 times from an armless chair as quickly as possible, the outcome is the time needed to perform the test. |
| Physical activity level as measured by accelerometry. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Number of accelerometer counts in 7 days. |
| Dialysis symptom index questionnaire score. | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | A validated questionnaire of 30 questions regarding the dialysis symptoms experienced during the last week. |
| Serum concentration of inflammatory mediator serum amyloid A (SAA). | At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline). | Blood for the laboratory measurements of total seum amyloid A concentration will be taken from the arterial line before the start of midweek hemodialysis procedure. |
Countries
Slovenia
Contacts
Primary ContactJernej Pajek, MH, PhD
Backup ContactTjaša Vivoda, MD
Outcome results
None listed