Impact of Microvascular Inflammation on Kidney Allograft Outcome

NCT ID: NCT06496269

Last Updated: 2024-07-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2023-12-31

Brief Summary

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.

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.

Conditions

Transplant;Failure,Kidney; Kidney Transplant Rejection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

No intervention

No intervention

Intervention Type: OTHER

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Paris Translational Research Center for Organ Transplantation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre Loupy

Role: PRINCIPAL_INVESTIGATOR

Paris Institute for Transplantation and Organ Regeneration

Locations

Pediatric Nephrology, UCLA Mattel Children's Hospital

Los Angeles, California, United States

Division of Pediatric Nephrology, Children's Pediatric Institute

Atlanta, Georgia, United States

Division of Pediatric Nephrology, Children's Mercy Hospital

Kansas City, Missouri, United States

Acute Dialysis Units, Pediatric Kidney Transplant

Charleston, South Carolina, United States

Division of Pediatric Nephrology and Hypertension, Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Department of Pediatrics, Seattle Children's Hospital

Seattle, Washington, United States

Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Bordeaux University Hospital, Department of Nephrology, Transplantation, Dialysis and Apheresis

Bordeaux, , France

Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon

Lyon, , France

Department of Nephrology, Centre Hospitalier Universitaire de Montpellier

Montpellier, , France

Nantes University Hospital, Department of Nephrology

Nantes, , France

Division of Pediatric Nephrology, Necker Hospital, AP-HP

Paris, , France

Division of Pediatric Nephrology, Robert Debré Hospital, AP-HP

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

Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Toulouse

Toulouse, , France

Department of Nephrology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Berlin Institute of Health

Berlin, , Germany

Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital

Barcelona, , Spain

Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals,

Geneva, , Switzerland

Countries

United States; France; Germany; Spain; Switzerland

References

Sablik M, Sannier A, Raynaud M, Goutaudier V, Divard G, Astor BC, Weng P, Smith J, Garro R, Warady BA, Zahr RS, Twombley K, Dharnidharka VR, Dandamudi RS, Fila M, Huang E, Sellier-Leclerc AL, Tonshoff B, Rabant M, Verine J, Del Bello A, Berney T, Boyer O, Catar RA, Danger R, Giral M, Yoo D, Girardin FR, Alsadi A, Gourraud PA, Morelon E, Le Quintrec M, Try M, Villard J, Zhong W, Bestard O, Budde K, Chauveau B, Couzi L, Brouard S, Hogan J, Legendre C, Anglicheau D, Aubert O, Kamar N, Lefaucheur C, Loupy A. Microvascular Inflammation of Kidney Allografts and Clinical Outcomes. N Engl J Med. 2025 Feb 20;392(8):763-776. doi: 10.1056/NEJMoa2408835. Epub 2024 Oct 24.

Reference Type: DERIVED

PMID: 39450752 (View on PubMed)

Other Identifiers

MVI_Kidney_002

Identifier Type: -

Identifier Source: org_study_id