T Regulatory Cells in Hemodialysis Patients: Observational Study

Completed

• Conditions: Haemodialysis Complication; Immune Dysfunction

• Registration Number: NCT02981992
• Lead Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Brief Summary

In this observational study, the investigators evaluated the Treg number and function in a population of patients undergoing hemodialysis (HD).

In particular, the investigators considered the relationship of Treg cell status with the different HD modalities and clinical parameters.

Detailed Description

Patients on hemodialysis (HD) present an elevated risk of cardiovascular disease, cancer and infectious events that may lead to the high morbidity and mortality rate characteristic of this population. Many causes can explain this increased risk, including inflammation that, in turn, might be secondary to dialysis-specific factors, such as contaminated water, dialysis modality and dialysis membranes used for treatment.

In addition to chronic inflammatory, in HD patients is also present a significant alteration of the immune system resulting in chronic lymphocytic infiltration, alteration of T-helper balance (Th1/Th2) etc. The immune response is controlled by very complex mechanisms; it is mediated by interaction between antigen-presenting cells (APC), CD4+ T helper (Th) and T cells CD4+ CD25+ regulatory (Treg), a cell subpopulation of T CD4+ expressing the IL-2 receptor (CD25) and forkhead factor (foxp 3). Treg cells contribute to the maintenance of peripheral tolerance by suppressing the immune response to self-normal or tumor antigens. Treg cells control population's expansion of peripheral cells and suppress the proliferation of Th activated cells. Accessory molecules such as CTLA-4 receptors, CD28 and IL-2 cytokines and IL-6, contribute to the activation and proliferation of Treg cells.

The characterization by flow cytometry of Treg suffered for a lack of specific surface markers. These cells are generally identified on the basis of contemporary expression of molecules CD4 and CD25, but the specificity of these markers is limited, given that the CD25 is also expressed on activated lymphocytes. Recently it has been showed that the expression of Foxp3 gene is a phenomenon strictly linked to the development of regulatory activity of Treg, and so, the extent of the expression of this gene by Real Time PCR is currently considered the most specific Treg marker. There is very poor data on Treg cells function in HD. A recent study shows that in patients on chronic HD, the number of Treg is lower if compared to healthy subjects. Moreover, the Treg cells of patients on HD would present a significant impairment of their function, assessed as the ability to inhibit lymphocyte proliferation.

Those results, however, are affected by the lack of data on the characteristics of the studied patients and the type of dialysis treatment applied. In contrast, a recent study by our group showed that patients on hemodialysis with poor biocompatible membranes have a greater number of circulating Treg compared with healthy controls matched for age and sex.

Given the absence of other data, it still remains to investigate the actual significance and function of Treg in HD, considering that Treg status might potentially affect the immune response.

Therefore, the purpose of this study was to evaluate the structure and function of Treg cells in patients undergoing HD, also considering their relationship with the different HD modalities and clinical parameters.

Study Timeline

• Study Start: 2011-02
• Primary Completion: 2014-02
• Study Completion: 2016-02
• Status Verified: 2016-11
• Study First Submitted: 2016-11-26
• Study First Submitted QC: 2016-12-02
• Last Update Submitted: 2016-12-02
• Study First Posted: 2016-12-05
• Last Update Posted: 2016-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patients with spKt/V ≥ 1,2

Exclusion Criteria

• Cancer
• Pregnant or breastfeeding
• Sepsis
• Kidney or other organ transplant
• Major cardiovascular events in the previous 3 months
• Patients unable to understand or interdicted

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treg number	Assessment of Treg number at basal control and then every 3 months for a total study period of 12 months	Assessment of the number of Treg by flow cytometry.

Secondary Outcome Measures

Name	Time	Method
Treg function	Assessment of Treg function at basal control and then every 3 months for a total study period of 12 months	Evaluation of Treg function by measuring the ability to inhibit cell proliferation in the context of a mixed lymphocyte reaction.
Effect of dialysis modality	Analysis of the number and function of Treg cells in function of the type of dialysis treatment at basal control and then every 6 months for a total study period of 12 months	Evaluation of the number and function of Treg cells before and after dialysis (by flow cytometry and in vitro experiments), as a function of the type of dialysis treatment by use of multivariate regression models

Trial Locations

Locations (1)

Fondazione Policlinico "San Matteo"; 🇮🇹 Pavia, Italy