Clinical trial NCT06496269: Impact of Microvascular Inflammation on Kidney Allograft Outcome
Official title: Impact of Microvascular Inflammation on Kidney Allograft Outcome: a Multinational Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Transplant;Failure,Kidney
Kidney Transplant Rejection
Lead sponsor: Paris Translational Research Center for Organ Transplantation
Sponsor class: OTHER
First posted: 2024-07-11
Enrollment: 6000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

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.

Primary outcomes:
measure: Microvascular inflammation-related diagnoses according to the Banff 2022 Classification
timeFrame: March 2004 to December 2023
measure: Kidney allograft loss
timeFrame: March 2004 to December 2023
Secondary outcomes:
measure: Transplant glomerulopathy
timeFrame: March 2004 to December 2023
measure: (Recurrent) antibody-mediated rejection episode
timeFrame: March 2004 to December 2023
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Pediatric Nephrology, UCLA Mattel Children's Hospital
state: California
city: Atlanta
country: United States
facility: Division of Pediatric Nephrology, Children's Pediatric Institute
state: Georgia
city: Kansas City
country: United States
facility: Division of Pediatric Nephrology, Children's Mercy Hospital
state: Missouri
city: Charleston
country: United States
facility: Acute Dialysis Units, Pediatric Kidney Transplant
state: South Carolina
city: Memphis
country: United States
facility: Division of Pediatric Nephrology and Hypertension, Le Bonheur Children's Hospital
state: Tennessee
city: Seattle
country: United States
facility: Department of Pediatrics, Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health
state: Wisconsin
city: Bordeaux
country: France
facility: Bordeaux University Hospital, Department of Nephrology, Transplantation, Dialysis and Apheresis
city: Lyon
country: France
facility: Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon
city: Montpellier
country: France
facility: Department of Nephrology, Centre Hospitalier Universitaire de Montpellier
city: Nantes
country: France
facility: Nantes University Hospital, Department of Nephrology
city: Paris
country: France
facility: Division of Pediatric Nephrology, Necker Hospital, AP-HP
city: Paris
country: France
facility: Division of Pediatric Nephrology, Robert Debré Hospital, AP-HP
city: Paris
country: France
facility: Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris
city: Paris
country: France
facility: Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris
city: Toulouse
country: France
facility: Department of Nephrology-Dialysis-Transplantation, Centre Hospitalier Universitaire de Toulouse
city: Berlin
country: Germany
facility: Department of Nephrology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Berlin Institute of Health
city: Barcelona
country: Spain
facility: Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital
city: Geneva
country: Switzerland
facility: Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals,
Study officials:
affiliation: Paris Institute for Transplantation and Organ Regeneration
name: Alexandre Loupy
role: PRINCIPAL_INVESTIGATOR
References: