Pre-formed Alloreactivity in Renal Transplant Recipients

The Role of Pre-formed Alloreactive T Cells on Acute Rejection Episodes and Long-term Graft Outcome in Patients After Living Donor Renal Transplantation

This investigator-initiated study will analyse the role of pre-formed alloreactive T cells on acute rejection episodes and graft outcome in kidney transplant recipients after living donation.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; Acute Graft Rejection

Detailed Description

In recipients of solid organ transplants, preformed alloreactive T cells may mediate acute rejections and compromise long-term graft survival. Previous studies on the role of alloreactive T cells in transplantation were hampered by the fact that experimental assays to quantify alloreactivity were technically demanding and not suitable for use in a clinical setting. Based on a recent development of a whole-blood assay, alloreactive T cells may be quantified and characterised within one day. This assay therefore provides the experimental basis to study the development and the role of alloreactive T cells in a clinical setting in patients after renal transplantation. This will be performed in a multicenter study in living donor renal transplant recipients where preformed alloreactivity of the recipient towards the living donor will be determined and associated with standard clinical parameters of graft function and long-term graft outcome on follow-up. In addition, the development of donor-specific antibodies will be analysed after transplantation. If this project was able to provide evidence for a role of alloreactive T cells in acute rejection episodes or long-term graft function, this assay may in future be used to guide individualized immunosuppressive drug treatment early after transplantation. It will thereby aid in distinguishing patients where standard immunosuppressive drug regimens are sufficient from the minor population of patients at high risk for rejection who will benefit from intensified drug regimens.

• Study Type: Observational
• Enrollment (Actual): 190

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Medizinische Klinik II, Aachen University
  • Berlin, Germany, 10117
    • Charite Berlin
  • Erlangen, Germany, 91054
    • University Erlangen Nürnberg
  • Frankfurt, Germany, 60596
    • Medizinische Klinik III, Frankfurt University
  • Gießen, Germany, 35392
    • University Clinic of Giessen and Marburg (UKGM)
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg Eppendorf
  • Heidelberg, Germany, 69120
    • Transplantationszentrum Heidelberg - Nephrologie
  • Köln, Germany, 50935
    • Klinikum Köln-Lindenthal
  • Lubeck, Germany, 23538
    • University of Lubeck
  • Mainz, Germany, 55131
    • University of Mainz
  • Muenster, Germany
    • University of Munster
  • Tübingen, Germany, 72076
    • Innere Medizin IV, University of Tübingen
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Saarland University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Transplant recipients of a kidney from a living donor

Description

Inclusion Criteria:

• Written informed consent
• First or second renal transplantation
• Living donor renal transplantation
• Recipient older than 18 years
• Negative cross match
• Planed quadruple, Tacrolimus-based (low-dose) immunosuppressive drug regimen (Tacrolimus, 2g MMF starting dose, (methyl)prednisolone according to center practice, basiliximab at day 0 and day 4)
• Planned start of Tacrolimus (Advagraf®) 3 to 10 days prior to transplantation (trough levels 5-10 ng/ml during the first 3 months, 5-7 ng/ml thereafter)

Exclusion Criteria:

• Planed T-cell depleting induction therapy
• Pregnancy
• Pre-existing, moderate to high dose immunosuppressive medication
• Pre-existing, severe lymphopenia (< 400/µl)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
kidney transplant recipients; kidney transplant recipients of an allograft from a living donor, no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
graft function	1-year graft function (estimated glomerular filtration rate)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Creatinine	1-year creatinine	1 year
Cystatin C	1-year cystatin C	1 year
rejection: acute rejection episodes within the first year		1 year
proteinuria within the first year		1 year

Collaborators and Investigators

• Sponsor: Martina Sester

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: alloreactive T cell; donor-specific antibody
• Other Study ID Numbers: Pre-formed alloreactivity

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO