T Regulatory Cells in Hemodialysis Patients: Observational Study

NCT ID: NCT02981992

Last Updated: 2016-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-02-28

Study Completion Date

2016-02-29

Brief Summary

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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

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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.

Conditions

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Haemodialysis Complication Immune Dysfunction

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role lead

Responsible Party

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Carmelo Libetta

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carmelo Libetta, Prof

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico "San Matteo", Pavia- Italy

Locations

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Fondazione Policlinico "San Matteo"

Pavia, , Italy

Site Status

Countries

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Italy

References

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Hendrikx TK, van Gurp EA, Mol WM, Schoordijk W, Sewgobind VD, Ijzermans JN, Weimar W, Baan CC. End-stage renal failure and regulatory activities of CD4+CD25bright+FoxP3+ T-cells. Nephrol Dial Transplant. 2009 Jun;24(6):1969-78. doi: 10.1093/ndt/gfp005. Epub 2009 Feb 4.

Reference Type BACKGROUND
PMID: 19193737 (View on PubMed)

Sewgobind VD, van der Laan LJ, Kho MM, Kraaijeveld R, Korevaar SS, van Dam T, Ijzermans JN, Weimar W, Baan CC. Characterization of rabbit antithymocyte globulins-induced CD25+ regulatory T cells from cells of patients with end-stage renal disease. Transplantation. 2010 Mar 27;89(6):655-66. doi: 10.1097/TP.0b013e3181c9cc7a.

Reference Type BACKGROUND
PMID: 20164820 (View on PubMed)

Sharif MR, Chitsazian Z, Moosavian M, Raygan F, Nikoueinejad H, Sharif AR, Einollahi B. Immune disorders in hemodialysis patients. Iran J Kidney Dis. 2015 Mar;9(2):84-96.

Reference Type BACKGROUND
PMID: 25851286 (View on PubMed)

Uda S, Mizobuchi M, Akizawa T. Biocompatible characteristics of high-performance membranes. Contrib Nephrol. 2011;173:23-29. doi: 10.1159/000328941. Epub 2011 Aug 8.

Reference Type BACKGROUND
PMID: 21865772 (View on PubMed)

Libetta C, Esposito P, Sepe V, Portalupi V, Margiotta E, Canevari M, Dal Canton A. Dialysis treatment and regulatory T cells. Nephrol Dial Transplant. 2010 May;25(5):1723-7. doi: 10.1093/ndt/gfq055. Epub 2010 Feb 15. No abstract available.

Reference Type RESULT
PMID: 20157169 (View on PubMed)

Sepe V, Gregorini M, Rampino T, Esposito P, Coppo R, Galli F, Libetta C. Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging. BMC Nephrol. 2019 Nov 15;20(1):412. doi: 10.1186/s12882-019-1585-6.

Reference Type DERIVED
PMID: 31729973 (View on PubMed)

Other Identifiers

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20100014090

Identifier Type: -

Identifier Source: org_study_id