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

Overview

Patients receiving maintenance hemodialysis are at increased risk of cardiovascular disease, chronic inflammation, endothelial dysfunction, and impaired quality of life. Medium cut-Off (MCO) hemodialysis membranes have been developed to enhance the removal of middle-molecular-weight uremic toxins compared with conventional high-flux membranes, which may improve inflammatory status and cardiovascular health. The aim of this study is to compare the effects of MCO and high-flux hemodialysis membranes on inflammatory biomarkers and cardiovascular function in adult patients receiving maintenance hemodialysis. The primary outcomes are changes in serum interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) levels. Secondary outcomes include arterial stiffness assessed by pulse wave velocity (PWV), body composition assessed by Body Composition Monitor (BCM), handgrip strength, and patient-reported outcomes including quality of life, pruritus, and pain scores. This is a prospective, randomized, open-label, two-sequence, two-period crossover study conducted at Gazi University Faculty of Medicine. Thirty adult hemodialysis patients will be randomized to one of two treatment sequences. Participants in Sequence A will receive MCO dialysis membranes for the first 3 months followed by high-flux membranes for the next 3 months. Participants in Sequence B will receive high-flux membranes for the first 3 months followed by MCO membranes for the next 3 months. Blood samples and clinical assessments will be performed at baseline, month 3, and month 6. The study is expected to provide evidence regarding the effects of different dialysis membrane technologies on inflammation and cardiovascular health and may contribute to optimizing membrane selection in routine hemodialysis practice.

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.