Antibody-mediated Rejection, Immunosuppression, Kidney Transplantation
Conditions
Brief summary
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.
Interventions
PROCEDUREKidney Transplantation
All participants will receive a kidney transplantation from a living donor or deceased donor
COMBINATION_PRODUCTImmunosuppression
All participants will receive immunosuppresive drugs to prevent rejection of de kidney transplant graft.
PROCEDURENephrectomy (kidney donation)
All kidney donors will receive a nephrectomy for kidney donation
Sponsors
Dutch Kidney Foundation
UMC Utrecht
Leiden University Medical Center
Maastricht University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Radboud University Medical Center
University Medical Center Groningen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 1. Luminex positive DSAs ; or 2. Retransplantation with repeated mismatch ; or 3. Husband to wife donation (after fathering children); or 4. Offspring to mother donation
Exclusion criteria
* No immunological high risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Antibody-Mediated Rejection (ABMR) | within 12 months after transplantation | Incidence of Antibody-Mediated Rejection (ABMR) as histopathological diagnosis |
| Incidence of mixed Antibody-Mediated Rejection / T-Cell Mediated Rejection (ABMR/TCMR) | within 12 months after transplantation | Incidence of mixed Antibody-Mediated Rejection / T-Cell Mediated Rejection as histopathological diagnosis(ABMR/TCMR) as histopathological diagnosis |
| Kidney transplant function | at 12 months after transplantation | as measured by eGFR and proteinuria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Development of Human-Leukocyte Antigen (HLA) antibodies | At 3 and 12 months after transplantation | As measured by Luminex assay at 3 and 12 months |
| Development of non-HLA antibodies | At 3 and 12 months after transplantation | Development of non-HLA antibodies as measured by a cell-based endothelial assay |
| Kidney transplant survival | At 12 months after transplantation | Kidney transplant survival in patients experiencing ABMR versus those not experiencing ABMR |
Countries
Netherlands
Contacts
Primary ContactJan-Stephan Sanders, MD PhD
Backup ContactJoost van den Born, MD PhD
Outcome results
None listed