Randomized Cross-Over Comparison of Medium Cut-Off and High-Flux Hemodialysis Membranes

Cardiovascular disease remains the leading cause of morbidity and mortality in patients receiving maintenance hemodialysis. Chronic inflammation, endothelial dysfunction, vascular stiffness, and the accumulation of middle-molecular-weight uremic toxins are considered important contributors to adverse cardiovascular outcomes in this population. Conventional high-flux hemodialysis membranes provide effective small-solute clearance but have limited capacity for removing larger middle molecules involved in inflammation and vascular injury.

Medium cut-off (MCO) membranes have been developed to enhance the clearance of larger middle molecules while maintaining albumin retention within acceptable limits. Previous studies have suggested that MCO membranes may improve inflammatory profiles and patient-centered outcomes; however, data regarding their effects on endothelial dysfunction, arterial stiffness, body composition, and patient-reported outcomes remain limited.

This study is designed as a prospective, randomized, open-label, two-sequence, two-period crossover clinical investigation comparing MCO and high-flux hemodialysis membranes in maintenance hemodialysis patients. Participants will be randomized in a 1:1 ratio to one of two treatment sequences. Sequence A will receive MCO membranes during Period 1 (Months 0-3) followed by high-flux membranes during Period 2 (Months 3-6). Sequence B will receive high-flux membranes during Period 1 followed by MCO membranes during Period 2. This crossover design allows each participant to serve as his or her own control, thereby reducing inter-individual variability.

Study assessments will be performed at baseline, Month 3, and Month 6. In addition to routine laboratory testing performed during standard hemodialysis follow-up, blood samples will be obtained at baseline, Month 3, and Month 6 for the measurement of serum interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1). Cardiovascular assessment will include pulse wave velocity (PWV) measurement. Nutritional and body composition status will be evaluated using Body Composition Monitor (BCM) parameters, including overhydration, ECW/TBW ratio, intracellular water, lean tissue index, body cell mass, and phase angle. Functional status will be assessed by handgrip strength measurement. Patient-reported outcomes will be evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36), UP-Dial pruritus questionnaire, and Short-Form McGill Pain Questionnaire (SF-MPQ).

The primary objective is to compare the effects of MCO and high-flux membranes on IL-6 and VCAM-1 levels. Secondary objectives include evaluation of arterial stiffness, body composition, physical function, and patient-reported outcomes. The findings may provide clinically relevant evidence regarding membrane selection strategies in routine hemodialysis practice.

Inclusion criteria

• Age 18 to 80 years.
• Receiving maintenance hemodialysis for at least 6 months.
• Clinically stable and receiving thrice-weekly hemodialysis.
• Able to comply with study procedures, questionnaires, and scheduled assessments.
• Able and willing to provide written informed consent.

Exclusion criteria

• Acute infection at screening or enrollment.
• Major surgery within the previous 3 months.
• Active malignancy requiring ongoing treatment.
• Terminal illness with limited life expectancy.
• Physical or cognitive impairment preventing completion of study procedures or questionnaires.
• Inability or unwillingness to provide written informed consent.