Development and Validation of a Comprehensive Classification Automation System for Kidney Allograft Biopsies

Study Overview
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Brief Summary
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Since 1991, the Banff classification has been the gold standard for defining antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR), thereby guiding the treatment and management of transplant recipients. Starting from a pure histological approach, the classification has moved over the past three decades towards an integrated precision diagnosis system, which encompasses other expertise, such as immunology, immunogenetic, other basic sciences, biostatistics, data science, and artificial intelligence The counterpart of this constant refinement is that Banff rules are becoming complex to follow, with numerous possible scenarios leading to a high degree of inter-observer variability and misclassifications, which may lead to therapeutic consequences. The aims of this study are: To integrate and decode all Banff rules and develop a computer-based application - the Banff Automation System - which provides automated and reproducible diagnoses To validate the ability of the Banff Automation System to reclassify rejection diagnoses in multicenter cohort studies and clinical trials.

Detailed Description
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Despite considerable advances in the development of effective immunosuppressive therapies, allograft rejection remains the main cause of graft loss after kidney transplantation. Since 1991, the Banff classification has been the gold standard for defining antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR), thereby guiding the treatment and management of transplant recipients. Starting from a pure histological approach, the classification has moved over the past three decades towards an integrated precision diagnosis system, which encompasses other expertise, such as immunology, immunogenetic, other basic sciences, biostatistics, data science, and artificial intelligence The counterpart of this constant refinement is that Banff rules are becoming complex to follow, with numerous possible scenarios leading to a high degree of inter-observer variability and misclassifications, which may lead to therapeutic consequences. Hence, international transplant societies and regulatory agencies urgently appealed for a more comprehensible and reproducible classification, required for decision-making process and reliable surrogate endpoints, to further improve patients care and drug development. The aims of this study are: To integrate and decode all Banff rules and develop a computer-based application - the Banff Automation System - which provides automated and reproducible diagnoses To validate the ability of the Banff Automation System to reclassify rejection diagnoses in multicenter cohort studies and clinical trials. Based on the results, the investigators will provide a comprehensive, user-friendly, and open-access online application which might improve reproducibility and precision of biopsies' diagnoses, thereby reducing misclassifications, and path the way to standardize histology-based endpoints in observational studies and clinical trials, and post-transplant diagnostic and therapeutic's management of kidney transplant recipients.

Official Title
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Development, Application, and Validation of a Comprehensive Classification Automation System for Allograft Precision Diagnostics in Adult and Pediatric Kidney Transplant Biopsies

Conditions
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Kidney Transplant Rejection, Pathology

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant recipients At least one kidney transplant biopsy performed, assessed with the Banff classification Exclusion Criteria: Inadequate biopsy according to the Banff classification (number of glomeruli inferior less than seven) Missing data for Banff lesion scores Missing data for donor-specific antibody status Missing data for C4d (degradation product of the classic complement pathway) staining
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational cohort<br>Observational prospective cohort of kidney transplant allograft biopsies | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rejection-related diagnoses reclassified by the computer-based tool | Proportion of rejection-related diagnoses reclassified by the computer-based tool | 1 day (At time of a kidney allograft biopsy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft survival | Comparison of graft survival after diagnosis by the computer-based tool | 24 months post-kidney allograft biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Banff classification, Kidney transplantation, Precision diagnostic, Automation