Medium Cut-Off and High-Flux Membranes on Mineral and Bone Metabolism in Hemodialysis Patients (MBD-HD)

Prospective Comparative Evaluation of the Effects of Medium Cut-Off and High-Flux Hemodialysis Membranes on Mineral and Bone Metabolism Biomarkers and Body Composition in Maintenance Hemodialysis Patients

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemodialysis; Chronic Kidney Disease Mineral and Bone Disorder; End Stage Kidney Disease (ESKD)
• Intervention / Treatment: Device: Medium Cut-Off Hemodialysis Membrane; Device: High-Flux Hemodialysis Membrane

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Veysel Baran Tomar, M.D.; Phone Number: +905334133253; Email: veyselbarantomar@gazi.edu.tr

Study Locations

• Turkey (Türkiye)
  • Ankara
    • Ankara, Ankara, Turkey (Türkiye), 06500
      • Gazi University Faculty of Medicine, Department of Nephrology, Hemodialysis Unit
      • Contact: Veysel Baran Tomar, M.D.; Phone Number: +905334133253; Email: veyselbarantomar@gazi.edu.tr
      • Contact: Omer Faruk Akcay, Associate Professor; Phone Number: +905546992867; Email: omerfarukakcay@gazi.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A (MCO to High-Flux); Participants randomized to Sequence A will receive medium cut-off (MCO) hemodialysis membranes during Period 1 (Months 0-3), followed by high-flux hemodialysis membranes during Period 2 (Months 3-6). Hemodialysis will be performed three times weekly according to standard clinical practice. Serum fibroblast growth factor-23 (FGF-23), sclerostin, pulse wave velocity (PWV), body composition parameters, handgrip strength, and patient-reported outcomes will be assessed at baseline, Month 3, and Month 6.	Device: Medium Cut-Off Hemodialysis Membrane; 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.; Device: High-Flux Hemodialysis Membrane; 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.
Experimental: Sequence B (High-Flux to MCO); Participants randomized to Sequence B will receive high-flux hemodialysis membranes during Period 1 (Months 0-3), followed by medium cut-off (MCO) hemodialysis membranes during Period 2 (Months 3-6). Hemodialysis will be performed three times weekly according to standard clinical practice. Serum fibroblast growth factor-23 (FGF-23), sclerostin, pulse wave velocity (PWV), body composition parameters, handgrip strength, and patient-reported outcomes will be assessed at baseline, Month 3, and Month 6.	Device: Medium Cut-Off Hemodialysis Membrane; 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.; Device: High-Flux Hemodialysis Membrane; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Fibroblast Growth Factor-23 (FGF-23)	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Serum Sclerostin	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kidney Disease Quality of Life-36 (KDQOL-36) Score	Evaluation of patient-reported quality of life using the KDQOL-36 questionnaire.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in UP-Dial Pruritus Score	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Short-Form McGill Pain Questionnaire (SF-MPQ) Score	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Overhydration (OH)	Assessment of overhydration (OH, L) measured using the Body Composition Monitor (BCM).	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Extracellular Water to Total Body Water Ratio (ECW/TBW)	Assessment of the extracellular water to total body water ratio (ECW/TBW) using the Body Composition Monitor (BCM).	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Intracellular Water (ICW)	Assessment of intracellular water (ICW, L) using the Body Composition Monitor (BCM).	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Lean Tissue Index (LTI)	Assessment of lean tissue index (LTI, kg/m²) using the Body Composition Monitor (BCM).	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Body Cell Mass (BCM)	Assessment of body cell mass (BCM, kg) using the Body Composition Monitor.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Pulse Wave Velocity (PWV) Measured in m/s	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)
Change in Handgrip Strength Measured by Hand Dynamometer	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.	At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)

Collaborators and Investigators

• Sponsor: Gazi University
• Collaborators: Nipro Medical Corporation

Publications and helpful links

General Publications

• Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, Schneider A, Wanner C, Rosenkranz AR, Krieter DH. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172. doi: 10.1093/ndt/gfw310.
• Figurek A, Rroji M, Spasovski G. Sclerostin: a new biomarker of CKD-MBD. Int Urol Nephrol. 2020 Jan;52(1):107-113. doi: 10.1007/s11255-019-02290-3. Epub 2019 Oct 14.
• Kim HJ, Seong EY, Song SH. Medium cut-off dialyzer improves reduction ratios of large middle molecules associated with vascular calcification. Kidney Res Clin Pract. 2024 Nov;43(6):753-762. doi: 10.23876/j.krcp.23.061. Epub 2024 Jan 25.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pulse Wave Velocity; FGF-23; Sclerostin; End-Stage Kidney Disease; CKD-MBD; Handgrip Strength; Body Composition Monitor; High-Flux Hemodialysis; Medium Cut-Off Membrane
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Nutrition Disorders; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Bone Diseases, Metabolic; Parathyroid Diseases; Renal Insufficiency, Chronic; Avitaminosis; Deficiency Diseases; Malnutrition; Rickets; Calcium Metabolism Disorders; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Hyperparathyroidism; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Kidney Failure, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder; Sclerosteosis
• Other Study ID Numbers: GAZI-HD-MCO-MBD-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) are not planned to be shared publicly. The study involves a limited number of participants from a single center, and data will be retained and managed in accordance with institutional policies, ethical requirements, and applicable data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No