Functional Proteomics of Uremic Retention Solutes Associated With Immunosenescence, Inflammation and Impaired Adaptive Stress Response

This is a randomized controlled crossover trial (58) in order to characterize PBL damage and death rate in hemodialysis patients treated with membranes with different permeability, including protein-leaking dialysers.

The study will enroll fourty patients on regular 4-h three times per week hemodialysis (HD) of the dialysis unit of the "Fondazione IRCCS Policlinico San Matteo" (Pavia, Italy). Thirteen age and sex matched healthy individuals (Ctr) and ten CKD patients on peritoneal dialysis treatment (PD*) will be included as healthy and CKD-matched controls, respectively. Comparison between HD and PD patients is aimed to assess the effect of biocompatibility and protein leakage during the treatments

Study Overview

• Status: Active, not recruiting
• Conditions: Hemodialysis
• Intervention / Treatment: Device: HDF with PMMA; Device: HDF

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

Contacts and Locations

Study Locations

• Italy
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo di Pavia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Male or female adults at time of enrolment aged <90 years old and >18 years old
• Patients in stable standard bicarbonate HD regimen, for at least two months

Exclusion Criteria:

• Patients aged <18 years old and >90 years old
• Known hypersensitivity or allergy to class of drugs or the investigational product or inability to comply with the requirements of the protocol;
• Participation in another study with investigational drug within the 30 days preceding and during the present study;
• Enrolment of the investigator, his/her family members, employees and other dependent persons;
• Recent illness (within the previous 1 week);
• Severe anemia (Hb < 7 g/dl);
• Bacterial or viral active infections;

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: healthy individuals
Experimental: patients on regular hemodialysis (HD) HDF with high cut-off polymethylmethacrylate (PMMA) membranes	Device: HDF with PMMA; Hemodiafiltration with polymethyl methacrylate (PMMA)-based membrane; Device: HDF; Hemodiafiltration without polymethyl methacrylate (PMMA)-based membrane
Active Comparator: patients on regular hemodialysis (HD) with polysulfone membrane dialyzers (HDF)	Device: HDF with PMMA; Hemodiafiltration with polymethyl methacrylate (PMMA)-based membrane; Device: HDF; Hemodiafiltration without polymethyl methacrylate (PMMA)-based membrane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of the filters in term of the reduction of plasma HMWs and PBL death levels in a cross-over design	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of plasma proteins composition of the uremic retentates.		day 0, day 90, day 180
Pharmacological manipulation of the cellular redox in THP-1 human leukocytes exposed to uremic retention solutes.	Thiol metabolomics and pharmacological manipulation of the cellular redox in THP-1 human leukocytes exposed to uremic retention solutes	day 0, day 90, day 180
Proteomics studies of the role of GSTP hyperexpression in the modulation of Nrf2 expression and activity in uremic leukocytes.		day 0, day 90, day 180
Study on transcription factors alternative to Nrf2	Study on transcription factors alternative to Nrf2 using human and murine Nrf2 inhibited monocyte lines	day 0, day 90, day 180
Study of Nrf2/GSTP stress response pathway in the PBL and THP-1 human monocytes	Study of expression and activity of the Nrf2/GSTP stress response pathway in the PBL and THP-1 human monocytes exposed to isolated uremic retention solutes.	day 0, day 90, day 180
Study of cell death in PBL freshly isolated from study groups	Study of cell death in PBL freshly isolated from study groups before and after treatment with autologous and heterologous whole plasma or isolated HMW fractions (studies of the IPR mechanism)	day 0, day 90, day 180
Analysis of CD4+ cells from blood samples and assessment of inflammatory cytokines after LPS stimulation	Purification and culture of CD4+ cells from blood samples and assessment of inflammatory cytokines (IL-4, IL-10, IL-12 p70, IL-18, and IFNγ) after LPS stimulation	day 0, day 90, day 180
Determination of lymphocyte subpopulations ex vivo		day 0, day 90, day 180
Pathway analysis of the differentially expressed proteins of PBL and of principal component of complement system		day 0, day 90, day 180
Analysis of HMWs characteristic oxidative PTMs in plasma and PBL lysate samples collected		day 0, day 90, day 180

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): February 17, 2027
• Study Completion (Estimated): February 17, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: PROTEURS

Drug and device information, study documents

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