Role of T Helper 17 and Regulatory T Cells in Delayed Graft Function

Can T Helper 17 and Regulatory T Cells Explain the Pathophysiology of Delayed Graft Function in Renal Transplant Recipients?

Delayed graft function (DGF) increases risk of acute rejection after kidney transplantation (KTx). Interleukin-6, which is produced in DGF, is critical in directing naive T helper cells differentiation towards T helper 17 (Th17) and away from regulatory T (Treg) cells. The investigators hypothesize there is an increase in Th17 and a decrease in Treg expression in KTx recipients with DGF compared to those without, leading to immunologic consequences. The investigators will test their hypothesis by measuring in both groups expression of Th17, Treg, and related cytokines in blood, urine, kidney biopsy, and kidney preservation fluid, and correlating these results with immunologic events.

Study Overview

• Status: Unknown
• Conditions: Delayed Graft Function

Detailed Description

All adult recipients of a primary kidney transplant will be eligible. Subjects will have blood samples drawn from which we will isolate lymphocytes and analyze the Treg population based on surface markers as well as a functional assay. The measures of Treg function will be compared to outcomes including DGF, graft survival and graft function, as well as the development of immunological complications such as donor-specific antibody production, acute rejection, IFTA and opportunistic infection.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All kidney transplant recipients at our institution will be recruited prior to their operative procedure.

Description

Inclusion Criteria:

• Kidney transplant recipients

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Delayed graft function; These are patients in whom dialysis is required following transplantation.
Immediate function; These are patients in whom no dialysis is required and creatinine declines by >20% in the first 24 hours following transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft function	Kidney graft function as measured by GFR	1 year

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Astellas Pharma Canada, Inc.
• Investigators: Principal Investigator: Steven Paraskevas, MD PhD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Nguyen MT, Fryml E, Sahakian SK, Liu S, Cantarovich M, Lipman M, Tchervenkov JI, Paraskevas S. Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation. Transplantation. 2016 Feb;100(2):314-24. doi: 10.1097/TP.0000000000000942.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: October 30, 2010
• First Submitted That Met QC Criteria: November 1, 2010
• First Posted (Estimate): November 2, 2010

Study Record Updates

• Last Update Posted (Estimate): September 14, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function
• Other Study ID Numbers: 09-202-SDR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make the experimental data available to participants. Their clinical data, however, is available to them through their treating physician.