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Pre-formed Alloreactivity in Renal Transplant Recipients

Completed
Conditions
Kidney Transplantation
Acute Graft Rejection
Registration Number
NCT02633826
Lead Sponsor
Martina Sester
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
190
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
graft function1 year

1-year graft function (estimated glomerular filtration rate)

Secondary Outcome Measures
NameTimeMethod
Creatinine1 year

1-year creatinine

rejection: acute rejection episodes within the first year1 year
Cystatin C1 year

1-year cystatin C

proteinuria within the first year1 year

Trial Locations

Locations (13)

Medizinische Klinik II, Aachen University

🇩🇪

Aachen, Germany

University Erlangen Nürnberg

🇩🇪

Erlangen, Germany

Transplantationszentrum Heidelberg - Nephrologie

🇩🇪

Heidelberg, Germany

Klinikum Köln-Lindenthal

🇩🇪

Köln, Germany

Medizinische Klinik III, Frankfurt University

🇩🇪

Frankfurt, Germany

University Clinic of Giessen and Marburg (UKGM)

🇩🇪

Gießen, Germany

Innere Medizin IV, University of Tübingen

🇩🇪

Tübingen, Germany

Saarland University

🇩🇪

Homburg, Saarland, Germany

University of Münster

🇩🇪

Muenster, Germany

University of Mainz

🇩🇪

Mainz, Germany

Universitätsklinikum Hamburg Eppendorf

🇩🇪

Hamburg, Germany

University of Lübeck

🇩🇪

Lubeck, Germany

Charité Berlin

🇩🇪

Berlin, Germany

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