PROCARE2: Incidence, Course and Outcome of ABMR in Kidney Transplantation

Sponsor

University Medical Center Groningen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05140018

Collaborator

Dutch Kidney Foundation (Other), UMC Utrecht (Other), Leiden University Medical Center (Other), Maastricht University Medical Center (Other), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Erasmus Medical Center (Other), Radboud University Medical Center (Other), Amsterdam UMC, location VUmc (Other)

225

Enrollment

49.9

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Antibody-mediated Rejection Kidney Transplantation Immunosuppression	Procedure: Kidney Transplantation Combination Product: Immunosuppression Procedure: Nephrectomy (kidney donation)

Study Design

Study Type:

Observational

Anticipated Enrollment :

225 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Kidney Transplant Recipients with an immunological high risk for ABMR 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 All participants will receive a kidney transplantation from a living donor or deceased donor Combination Product: Immunosuppression All participants will receive immunosuppresive drugs to prevent rejection of de kidney transplant graft.
Living Kidney Donors Participants who are about to donate their kidney to a Recipient with a high immunological risk (as described above)	Procedure: Nephrectomy (kidney donation) All kidney donors will receive a nephrectomy for kidney donation

Arm

Intervention/Treatment

Kidney Transplant Recipients with an immunological high risk for ABMR

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

All participants will receive a kidney transplantation from a living donor or deceased donor

Combination Product: Immunosuppression

All participants will receive immunosuppresive drugs to prevent rejection of de kidney transplant graft.

Living Kidney Donors

Participants who are about to donate their kidney to a Recipient with a high immunological risk (as described above)

Procedure: Nephrectomy (kidney donation)

All kidney donors will receive a nephrectomy for kidney donation

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University Medical Center Groningen
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
Amsterdam UMC, location VUmc

Investigators

Study Chair: Hendrikus Otten, PhD, UMC Utrecht

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

J.S.F. Sanders, MD PhD, University Medical Center Groningen

ClinicalTrials.gov Identifier:

NCT05140018

Other Study ID Numbers:

PROCARE2

First Posted:

Dec 1, 2021

Last Update Posted:

Dec 1, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Dec 1, 2021