Efficacy and Safety of Super High-Flux Hemodialysis in Maintenance Dialysis Patients. SHINE-RLS (Super High-flux Dialysis Improves Neuro-symptoms and Efficacy in Restless Legs Syndrome)

Advancing Dialyzer Technology: Efficacy and Safety of Super High-Flux Hemodialysis in Maintenance Dialysis Patients

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.

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.

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