Pre-formed Alloreactivity in Renal Transplant Recipients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Kidney Transplantation, Acute Graft Rejection

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| kidney transplant recipients<br>kidney transplant recipients of an allograft from a living donor, no intervention | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alloreactive T cell, donor-specific antibody