Incidence, Course and Outcome of ABMR in Kidney Transplantation

Recruiting

• Conditions: Kidney Transplantation; Immunosuppression; Antibody-mediated Rejection
• Interventions: Procedure: Nephrectomy (kidney donation); Procedure: Kidney Transplantation; Combination Product: Immunosuppression

• Registration Number: NCT05140018
• Lead Sponsor: University Medical Center Groningen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-17
• Study First Submitted QC: 2021-11-17
• Study First Posted: 2021-12-01
• Study Start: 2022-01-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-05-11
• Primary Completion: 2025-01-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 225

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Living Kidney Donors	Nephrectomy (kidney donation)	Participants who are about to donate their kidney to a Recipient with a high immunological risk (as described above)
Kidney Transplant Recipients with an immunological high risk for ABMR	Kidney Transplantation	* Kidney transplant recipients ≥18 years old * About to receive a post mortal or living donor renal transplant * 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
Kidney Transplant Recipients with an immunological high risk for ABMR	Immunosuppression	* Kidney transplant recipients ≥18 years old * About to receive a post mortal or living donor renal transplant * 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

Primary Outcome Measures

Name	Time	Method
Incidence of Antibody-Mediated Rejection (ABMR)	within 12 months after transplantation	Incidence of Antibody-Mediated Rejection (ABMR) as histopathological diagnosis
Kidney transplant function	at 12 months after transplantation	as measured by eGFR and proteinuria
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

Secondary Outcome Measures

Name	Time	Method
Kidney transplant survival	At 12 months after transplantation	Kidney transplant survival in patients experiencing ABMR versus those not experiencing ABMR
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

Trial Locations

Locations (6)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

UMCU; 🇳🇱 Utrecht, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Academisch Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Radboud University Hospital; 🇳🇱 Nijmegen, Netherlands