Chronic Kidney Disease Mineral and Bone Disorder, End Stage Kidney Disease (ESKD), Hemodialysis
Conditions
Keywords
End-Stage Kidney Disease, High-Flux Hemodialysis, Medium Cut-Off Membrane, Pulse Wave Velocity, Body Composition Monitor, Handgrip Strength, FGF-23, Sclerostin, CKD-MBD
Brief summary
This study aims to compare the effects of medium cut-off (MCO) and high-flux hemodialysis membranes on mineral and bone metabolism biomarkers in patients receiving maintenance hemodialysis. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by disturbances in biomarkers such as fibroblast growth factor-23 (FGF-23) and sclerostin, which are associated with bone turnover, vascular calcification, and adverse clinical outcomes. This is a single-center, prospective, randomized, open-label, two-sequence, two-period crossover clinical study. Thirty adult patients receiving maintenance hemodialysis will be randomized to receive either MCO membrane treatment followed by high-flux membrane treatment or the reverse sequence, with each treatment period lasting three months. Serum FGF-23 and sclerostin levels will be measured at baseline, Month 3, and Month 6. Additional assessments will include pulse wave velocity (PWV), body composition monitoring (BCM), handgrip strength, health-related quality of life (KDQOL-36), pruritus severity (UP-Dial), and pain assessment (SF-MPQ). The study will evaluate whether MCO membranes provide additional benefits compared with conventional high-flux membranes regarding CKD-MBD-related biomarkers and patient-centered outcomes.
Detailed description
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication in patients receiving maintenance hemodialysis and is associated with abnormalities in mineral metabolism, bone turnover, vascular calcification, and increased cardiovascular risk. Biomarkers such as fibroblast growth factor-23 (FGF-23) and sclerostin play important roles in the pathophysiology of CKD-MBD and have been associated with adverse clinical outcomes in patients with end-stage kidney disease. 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. Because FGF-23 and sclerostin are relatively large circulating molecules, MCO membranes may provide improved clearance and potentially influence CKD-MBD-related biological pathways. This study is a single-center, prospective, randomized, open-label, two-sequence, two-period crossover clinical investigation conducted in maintenance hemodialysis patients. Eligible participants will be randomized in a 1:1 ratio to one of two treatment sequences. Sequence A will receive MCO hemodialysis for three months followed by high-flux hemodialysis for three months. Sequence B will receive high-flux hemodialysis for three months followed by MCO hemodialysis for three months. Assessments will be performed at baseline, Month 3, and Month 6. Primary outcome measures include changes in serum FGF-23 and sclerostin concentrations. Secondary outcome measures include changes in pulse wave velocity (PWV), body composition parameters measured by BCM, handgrip strength, health-related quality of life (KDQOL-36), pruritus severity (UP-Dial), and pain characteristics (SF-MPQ). Routine laboratory evaluations will be performed according to standard clinical practice. In addition, blood samples will be collected for FGF-23 and sclerostin measurements at each study visit. Safety assessments will include monitoring of adverse events, dialysis-related intolerance, and clinically significant medical events throughout the study period. The results of this study are expected to provide evidence regarding the effects of MCO membranes on CKD-MBD-related biomarkers and patient-centered outcomes and may contribute to optimizing membrane selection strategies in maintenance hemodialysis practice.
Interventions
A medium cut-off (MCO) hemodialysis membrane used during maintenance hemodialysis treatment. Participants assigned to MCO treatment will receive thrice-weekly hemodialysis according to standard clinical practice. The intervention is intended to enhance the removal of middle-molecular-weight solutes and to evaluate its effects on mineral and bone metabolism biomarkers, including fibroblast growth factor-23 (FGF-23) and sclerostin, as well as body composition, vascular stiffness, and patient-reported outcomes.
A conventional high-flux hemodialysis membrane used during maintenance hemodialysis treatment. Participants assigned to high-flux treatment will receive thrice-weekly hemodialysis according to standard clinical practice. This intervention serves as the comparator for evaluating the effects of medium cut-off membranes on mineral and bone metabolism biomarkers, including fibroblast growth factor-23 (FGF-23) and sclerostin, as well as body composition, vascular stiffness, and patient-reported outcomes.
Sponsors
Gazi University
Nipro Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. Participants, care providers, and investigators are aware of the assigned dialysis membrane. No masking procedures are planned.
Intervention model description
Participants will be randomized in a 1:1 ratio to one of two treatment sequences. Sequence A will receive medium cut-off (MCO) hemodialysis membranes during the first 3-month treatment period followed by high-flux membranes during the second 3-month treatment period. Sequence B will receive high-flux membranes during the first treatment period followed by MCO membranes during the second treatment period. Clinical and laboratory assessments will be performed at baseline, Month 3, and Month 6.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Fibroblast Growth Factor-23 (FGF-23) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Change in serum fibroblast growth factor-23 (FGF-23) concentrations during treatment with medium cut-off and high-flux hemodialysis membranes. Serum FGF-23 levels will be measured using ELISA and compared between treatment periods. |
| Change in Serum Sclerostin | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Change in serum sclerostin concentrations during treatment with medium cut-off and high-flux hemodialysis membranes. Serum sclerostin levels will be measured using ELISA and compared between treatment periods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulse Wave Velocity (PWV) Measured in m/s | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Pulse wave velocity (PWV) will be measured in meters per second (m/s) as a single parameter of arterial stiffness. Change in PWV from baseline to Month 3 and Month 6 will be compared between medium cut-off and high-flux hemodialysis membrane treatment periods. |
| Change in Handgrip Strength Measured by Hand Dynamometer | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Handgrip strength will be measured in kilograms (kg) using a hand dynamometer. The same prespecified measurement method will be used at each study visit. Change in handgrip strength from baseline to Month 3 and Month 6 will be compared between medium cut-off and high-flux hemodialysis membrane treatment periods. |
| Change in Kidney Disease Quality of Life-36 (KDQOL-36) Score | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Evaluation of patient-reported quality of life using the KDQOL-36 questionnaire. |
| Change in UP-Dial Pruritus Score | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Evaluation of pruritus severity using the Uraemic Pruritus in Dialysis Patients (UP-Dial) scale. The UP-Dial total score ranges from 0 to 56, with higher scores indicating more severe pruritus and a worse outcome. |
| Change in Short-Form McGill Pain Questionnaire (SF-MPQ) Score | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Evaluation of pain using the Short-Form McGill Pain Questionnaire (SF-MPQ) total Pain Rating Index score. The SF-MPQ total Pain Rating Index score is calculated from 15 pain descriptors, each scored from 0 to 3, resulting in a total score range of 0 to 45. Higher scores indicate greater pain severity and a worse outcome. |
| Change in Overhydration (OH) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Assessment of overhydration (OH, L) measured using the Body Composition Monitor (BCM). |
| Change in Extracellular Water to Total Body Water Ratio (ECW/TBW) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Assessment of the extracellular water to total body water ratio (ECW/TBW) using the Body Composition Monitor (BCM). |
| Change in Intracellular Water (ICW) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Assessment of intracellular water (ICW, L) using the Body Composition Monitor (BCM). |
| Change in Lean Tissue Index (LTI) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Assessment of lean tissue index (LTI, kg/m²) using the Body Composition Monitor (BCM). |
| Change in Body Cell Mass (BCM) | At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027) | Assessment of body cell mass (BCM, kg) using the Body Composition Monitor. |
Countries
Turkey (Türkiye)
Outcome results
None listed