Incidence, Course and Outcome of ABMR in Kidney Transplantation

Study Overview
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Brief Summary
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Rationale: Despite improved patient and graft survival in renal transplant recipients, still 20% of the patients reaches end-stage renal disease within 5 years after transplantation. Antibody-mediated rejection (ABMR) is one of the major causes of early graft loss and perhaps even more important of late deterioration of graft function Objective: Evaluate the occurrence of antibody mediated rejection (ABMR) and mixed ABMR and cellular/ T-cell mediated rejection (TCMR), in patients treated with the currently prevailing immunosuppressive regimens, and relate them to outcome (graft survival, function, proteinuria, histology) Study design: Clinical cohort study. Study population: patients of >18 years old, about to receive a post mortal of living donor renal transplant with an immunological high risk for ABMR. Main study parameters/endpoints: main study endpoints are the occurrence of ABMR, mixed ABMR/TCMR and renal function after 1 year of follow-up. The main study parameter will be mapping the immune system, including B-cells, (non-)HLA antibodies, interaction between B-cells and T follicular helper cells, and complete immune profiling.

Official Title
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Incidence, Course and Outcome of Cellular and Antibody-mediated Rejection in Immunological High-risk Kidney Transplantation, a Prospective Cohort PROCARE2 Study

Conditions
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Antibody-mediated Rejection, Kidney Transplantation, Immunosuppression

Intervention / Treatment
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* Procedure: Kidney Transplantation
* Combination Product: Immunosuppression
* Procedure: Nephrectomy (kidney donation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant recipients ≥18 years old About to receive a post mortal or living donor renal transplant written informed consent (is able to read of understand in Dutch) Immunological high risk for rejection Luminex positive DSAs ; or Retransplantation with repeated mismatch ; or Husband to wife donation (after fathering children); or Offspring to mother donation Exclusion Criteria: No immunological high risk

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 with an immunological high risk for ABMR<br>Kidney transplant recipients ≥18 years old About to receive a post mortal or living donor renal transplant Immunological high risk for rejection Luminex positive DSAs ; or Retransplantation with repeated mismatch ; or Husband to wife donation (after fathering children); or Offspring to mother donation | Procedure: Kidney Transplantation<br>* All participants will receive a kidney transplantation from a living donor or deceased donor<br>Combination Product: Immunosuppression<br>* All participants will receive immunosuppresive drugs to prevent rejection of de kidney transplant graft.<br>|
| Living Kidney Donors<br>Participants who are about to donate their kidney to a Recipient with a high immunological risk (as described above) | Procedure: Nephrectomy (kidney donation)<br>* All kidney donors will receive a nephrectomy for kidney donation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Antibody-Mediated Rejection (ABMR) | Incidence of Antibody-Mediated Rejection (ABMR) as histopathological diagnosis | within 12 months after transplantation | 
| Incidence of mixed Antibody-Mediated Rejection / T-Cell Mediated Rejection (ABMR/TCMR) | Incidence of mixed Antibody-Mediated Rejection / T-Cell Mediated Rejection as histopathological diagnosis(ABMR/TCMR) as histopathological diagnosis | within 12 months after transplantation | 
| Kidney transplant function | as measured by eGFR and proteinuria | at 12 months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Human-Leukocyte Antigen (HLA) antibodies | As measured by Luminex assay at 3 and 12 months | At 3 and 12 months after transplantation | 
| Development of non-HLA antibodies | Development of non-HLA antibodies as measured by a cell-based endothelial assay | At 3 and 12 months after transplantation | 
| Kidney transplant survival | Kidney transplant survival in patients experiencing ABMR versus those not experiencing ABMR | At 12 months after transplantation |