End Stage Renal Failure, Hemodialysis, Restless Leg Syndrome (RLS)
Conditions
Keywords
End-stage kidney disease, Restless leg syndrome, Super high-flux hemodialysis
Brief summary
Patients with end-stage kidney disease (ESKD) rely on maintenance hemodialysis. While high-flux hemodialysis improves small solute clearance, its removal of middle-molecule uremic toxins (e.g., α1-microglobulin \[α1-MG\]) remains insufficient, contributing to symptoms such as restless legs syndrome (RLS), pruritus, and poor sleep quality, which are also linked to increased cardiovascular risk. In this study, the investigators evaluate whether using a "Super High-Flux" dialyzer (a Type V high-performance dialyzer) during hemodialysis can safely improve the removal of middle-molecule uremic toxins-specifically α1-microglobulin (α1-MG)-and relieve RLS symptoms in maintenance hemodialysis patients.
Detailed description
Patients with end-stage kidney disease (ESKD) on regular high-flux hemodialysis (HD) often experience an accumulation of middle-molecule uremic toxins, which are linked to systemic inflammation and troubling symptoms such as restless legs syndrome (RLS), severe itching, and poor sleep quality. While traditional high-flux dialysis efficiently clears small molecules, its ability to remove larger middle-molecule toxins (like α1-microglobulin \[α1-MG\]) is limited. Current alternatives such as online hemodiafiltration (HDF) have limitations, highlighting the need for new treatment approaches. Super High-Flux Hemodialysis (SHFHD) offers enhanced clearance of these middle molecules while preserving serum albumin levels and maintaining patient safety. In this study, the investigators evaluate the effectiveness and safety of SHFHD compared with high-flux HD in patients undergoing maintenance HD, focusing on α1-MG removal and its potential effect on RLS. The investigators also explore the multiple diverse effects of SHFHD on the changes of cardiovascular risk factors including bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial metabolites in dialysis patients. It is to conduct a randomized, controlled, crossover trial with cross-over design at a dialysis unit of tertiary teaching hospital in Northern Taiwan. The investigators will stratify participants by baseline RLS. Participants will receive either SHFHD or high-flux HD for 12 weeks, followed by a 4-week washout and crossover. The study outcome measures are difference in change-from-baseline values of α1-MG reduction ratio, RLS severity (International Restless Legs Scale), albumin levels, clearance of β2-microglobulin, free light chains, inflammatory markers, pruritus scores, and quality of life. Safety will be assessed via albumin maintenance, adverse events, and hemodynamic stability. This will be the first RCT directly evaluating SHFHD for α1-MG removal and RLS outcomes, addressing critical knowledge gaps and potentially informing new dialysis prescription strategies.
Interventions
DEVICESuper High-Flux HD
Participants receive hemodialysis using a Type V super high-flux dialyzer (such as Elisio™-HX or Theranova) for 12 weeks to assess the clearance of middle-molecule uremic toxins and its effect on RLS symptoms.
Sponsors
Far Eastern Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Laboratory technicians who assess the study outcomes will be masked
Intervention model description
A randomized, active-controlled trial with cross-over design
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Restless Legs Syndrome according to standard criteria. 2. Age ≥ 20 years. 3. Maintenance high-flux hemodialysis for ≥ 3 months. 4. Stable vascular access (AV fistula or AV graft). 5. Adequate dialysis delivery (URR ≥ 65% or Kt/V(daugirdes) ≥ 1.2). 6. Sufficient iron stores (serum ferritin ≥ 200 ng/mL, TSAT ≥ 20%). 7. Clinically stable condition for the past 4 weeks. 8. Able and willing to comply with study protocol
Exclusion criteria
1. Low-flux HD or temporary catheter use 2. Serum albumin \< 2.5 g/dL 3. Recent hospitalization (within 4 weeks) 4. Scheduled kidney transplantation 5. Active malignancy or infection 6. Pregnancy 7. Any condition impairing protocol adherence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in α1-microglobulin (α1-MG) Reduction Ratio | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | The reduction ratio of α1-MG will be calculated as \[({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}\] at each study visit. The primary outcome is the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in International Restless Legs Scale (IRLS) Score | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | IRLS score assesses the severity of Restless Legs Syndrome (ranging from 0 to 40, where higher scores indicate greater severity). Evaluated as the difference in score changes between the two treatment periods. |
| Change from Baseline in Pre-dialysis Serum Albumin Level | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Monitored to evaluate nutritional safety and albumin preservation during Super High-Flux HD compared to High-Flux HD. |
| Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Assesses sleep quality. Evaluated as the difference in score changes between the two treatment periods. |
| Change from Baseline in 5-D Itch Scale Score | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Assesses pruritus severity. Evaluated as the difference in score changes between the two treatment periods. |
| Change from Baseline in health-related quality of life (EQ-5D-5L) Score | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Assesses quality of life. Evaluated as the difference in score changes between the two treatment periods. |
| Change from Baseline in β2-microglobulin [β2-MG] Reduction ratio | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | The reduction ratio of β2-MG will be calculated as \[({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}\] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Kappa Free Light Chains Reduction ratio | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | The reduction ratio will be calculated as \[({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}\] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Lambda Free Light Chains Reduction ratio | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | The reduction ratio will be calculated as \[({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}\] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Pre-dialysis Serum interleukin-6 (IL-6) Level | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Pre-dialysis Serum High-sensitivity C-reactive Protein (hs-CRP) Level | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Pre-dialysis Serum Indoxyl Sulfate Level | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period. |
| Change from Baseline in Pre-dialysis Serum P-cresol Sulfate Level | Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period | Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period. |
Countries
Taiwan
Contacts
CONTACTWan-Chuan Tsai, M.D., Ph.D.
Outcome results
None listed