Incidence, Course and Outcome of ABMR in Kidney Transplantation (PROCARE2)

May 9, 2023 updated by: J.S.F. Sanders, University Medical Center Groningen

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

225

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jan-Stephan Sanders, MD PhD
  • Phone Number: +31503612955
  • Email: j.sanders@umcg.nl

Study Contact Backup

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Academisch Medisch Centrum
        • Contact:
          • Frederike Bemelman, MD, PhD
        • Principal Investigator:
          • Frederike Bemelman, MD, PhD
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
        • Principal Investigator:
          • Jan-Stephan Sanders, MD, PhD
        • Contact:
      • Leiden, Netherlands
        • Recruiting
        • Leiden University Medical Center
        • Contact:
          • Aiko de Vries, MD, PhD
        • Principal Investigator:
          • Aiko de Vries, MD, PhD
      • Nijmegen, Netherlands
        • Recruiting
        • Radboud University Hospital
        • Contact:
          • Marije Baas, MD, PhD
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus MC
        • Contact:
          • Dennis Hesselink, MD, PhD
      • Utrecht, Netherlands
        • Recruiting
        • UMCU
        • Contact:
          • Arjan Van Zuilen, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients with eind-stage renale disease (ESRD) who are about to receive a kidney transplant from a living or deceased donor, with an elevated immunological risk (higher risk for (antibody-mediated) rejection).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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

    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
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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

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

Investigators

  • Study Chair: Hendrikus Otten, PhD, UMC Utrecht

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2022

Primary Completion (Anticipated)

January 1, 2025

Study Completion (Anticipated)

March 1, 2026

Study Registration Dates

First Submitted

November 17, 2021

First Submitted That Met QC Criteria

November 17, 2021

First Posted (Actual)

December 1, 2021

Study Record Updates

Last Update Posted (Estimate)

May 11, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • PROCARE2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe