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)

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 tosystemic inflammation and troubling symptoms such as restless legs syndrome (RLS), severeitching, and poor sleep quality. While traditional high‐flux dialysis efficiently clearssmall molecules, its ability to remove larger middle‐molecule toxins (likeα1‐microglobulin [α1‐MG]) is limited. Current alternatives such as onlinehemodiafiltration (HDF) have limitations, highlighting the need for new treatmentapproaches. Super High‐Flux Hemodialysis (SHFHD) offers enhanced clearance of thesemiddle molecules while preserving serum albumin levels and maintaining patient safety.In this study, the investigators evaluate the effectiveness and safety of SHFHD comparedwith high‐flux HD in patients undergoing maintenance HD, focusing on α1‐MG removal andits potential effect on RLS. The investigators also explore the multiple diverse effectsof SHFHD on the changes of cardiovascular risk factors including bone turnover, mineralmetabolism, 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 adialysis unit of tertiary teaching hospital in Northern Taiwan. The investigators willstratify participants by baseline RLS. Participants will receive either SHFHD orhigh‐flux HD for 12 weeks, followed by a 4‐week washout and crossover. The study outcomemeasures are difference in change‐from‐baseline values of α1‐MG reduction ratio, RLSseverity (International Restless Legs Scale), albumin levels, clearance ofβ2‐microglobulin, free light chains, inflammatory markers, pruritus scores, and qualityof life. Safety will be assessed via albumin maintenance, adverse events, and hemodynamicstability.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 prescriptionstrategies.