Impact of Microvascular Inflammation on Kidney Allograft Outcome

Impact of Microvascular Inflammation on Kidney Allograft Outcome: a Multinational Cohort Study

Graft microvascular inflammation poses a significant challenge to successful kidney transplantation due to its heterogeneous clinical presentation. There is a critical need to unravel the clinical significance of newly defined allograft microvascular inflammation phenotypes in the Banff 2022 classification and assess the implications of these new phenotypes on kidney transplant precision diagnostics and patient risk stratification.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Rejection; Transplant;Failure,Kidney
• Intervention / Treatment: Other: No intervention

Detailed Description

Antibody-mediated rejection is a major cause of graft failure in kidney transplant recipients, with allograft microvascular inflammation serving as the hallmark histological lesion of antibody-mediated graft injury. However, the frequent occurrence of graft microvascular inflammation in the absence of circulating anti-HLA donor-specific antibodies highlights the incomplete understanding of the mechanisms underlying this inflammation. This heterogenous presentation poses a significant challenge in the clinical setting, as current treatment strategies often prove ineffective, hindering the improvement of allograft and patient care. The Banff 2022 classification update has reappraised lesions of microvascular inflammation, identifying new diagnostic phenotypes of microvascular inflammation. However, the clinical significance of these phenotypes is yet to be determined.

The aims of this study are:

1. To determine the impact of the revised Banff 2022 Classification on the diagnostic classification of phenotypes related to microvascular inflammation, compared to previous Banff 2019 Classification.
2. To assess the association of microvascular inflammation phenotypes with kidney allograft survival.
3. To assess the association of microvascular inflammation phenotypes with disease progression, defined by transplant glomerulopathy occurrence (cg and subsequent antibody-mediated rejection episodes.

• Study Type: Observational
• Enrollment (Actual): 6000

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Bordeaux University Hospital, Department of Nephrology, Transplantation, Dialysis and Apheresis
  • Lyon, France
    • Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon
  • Montpellier, France
    • Department of Nephrology, Centre Hospitalier Universitaire de Montpellier
  • Nantes, France
    • Nantes University Hospital, Department of Nephrology
  • Paris, France
    • Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris
  • Paris, France
    • Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris
  • Paris, France
    • Division of Pediatric Nephrology, Necker Hospital, AP-HP
  • Paris, France
    • Division of Pediatric Nephrology, Robert Debré Hospital, AP-HP
  • Toulouse, France
    • Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Toulouse
• Germany
  • Berlin, Germany
    • Department of Nephrology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Berlin Institute of Health
• Spain
  • Barcelona, Spain
    • Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital
• Switzerland
  • Geneva, Switzerland
    • Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals,
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Pediatric Nephrology, UCLA Mattel Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Division of Pediatric Nephrology, Children's Pediatric Institute
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Division of Pediatric Nephrology, Children's Mercy Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Acute Dialysis Units, Pediatric Kidney Transplant
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Division of Pediatric Nephrology and Hypertension, Le Bonheur Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Department of Pediatrics, Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Kidney transplant recipients of all sexes recruited in observational studies performed in Europe and United States, with at least one kidney biopsy performed with all the relevant data to provide a diagnosis according to the 2019 and 2022 Banff classification, including clinical data (recipient and donor's age, sex and transplant characteristics).

Description

Inclusion Criteria:

• Kidney transplant recipients, with at least one kidney transplant biopsy performed, assessed with the Banff classification.

Exclusion Criteria:

• Missing data for a rejection-related diagnosis according to the 2019 and 2022 Banff classification.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Microvascular inflammation-related diagnoses according to the Banff 2022 Classification	March 2004 to December 2023
Kidney allograft loss	March 2004 to December 2023

Secondary Outcome Measures

Outcome Measure	Time Frame
Transplant glomerulopathy	March 2004 to December 2023
(Recurrent) antibody-mediated rejection episode	March 2004 to December 2023

Collaborators and Investigators

• Sponsor: Paris Translational Research Center for Organ Transplantation
• Investigators: Principal Investigator: Alexandre Loupy, Paris Institute for Transplantation and Organ Regeneration

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Inflammation; Renal Insufficiency
• Other Study ID Numbers: MVI_Kidney_002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data analyzed during the current study are available on reasonable request including standards for General Data Protection Regulation and Institutional Review Board approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No