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Microvascular inflammation in kidney allografts has been widely reappraised in the recent update of Banff classification. There is a critical need to better understand the pathophysiological mechanisms associated with the various phenotypes of microvascular inflammation that are observed in kidney transplants, particularly in order to develop targeted therapeutic approaches.
Antibody-mediated rejection is a major cause of graft failure in kidney transplant recipients. The diagnostic criteria for antibody-mediated rejection have undergone significant changes since their initial definition in the international Banff Classification system. The Banff 2022 Classification update reappraises lesions of microvascular inflammation and identifies new phenotypes for cases with microvascular inflammation. However, pathophysiological mechanisms associated with microvascular inflammation in kidney allografts are still poorly understood, thus hampering the development of efficient treatments.
The aims of this study are:
The investigators will use a multimodal phenotyping approach including histological analyses and multiplex immunostainings, bulk transcriptomic analyses and spatial whole-transcriptome digital profiling to decipher the molecular landscape of microvascular inflammation in kidney allografts. Based on these results, they will investigate its association with allograft outcomes and search for molecular targets which could benefit from targeted therapeutic strategies.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No intervention | Other | No intervention |
| Measure | Description | Time Frame |
|---|---|---|
| RNA-based molecular signatures assessed using bulk and spatial transcriptomics | 1 day (at time of a kidney allograft biopsy) | |
| Probability of graft survival based on outcome data | 24 months post-kidney allograft biopsy | |
| Probability of patient survival on outcome data | 24 months post-kidney allograft biopsy |
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Inclusion Criteria:
- Adult kidney transplant recipients, with at least one kidney transplant biopsy performed and assessed according to the international Banff 2022 classification, with or without lesions of microvascular inflammation
Exclusion Criteria:
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Adult kidney transplant recipients of all sexes (self-determined) recruited in Europe and United States, who had a kidney allograft biopsy with or without lesions of microvascular inflammation (adequate biopsies without missing data for Banff lesion scores, donor-specific antibody status, and C4d staining), according to the international Banff 2022 classification.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alexandre Loupy, MD PhD | Contact | +33612491082 | alexandreloupy@inserm.fr | |
| Catherine Tritscher | Contact | +33153988000 | tritschercatherine@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris | Recruiting | Paris | 75010 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32463180 | Background | Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel M. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020 Sep;20(9):2318-2331. doi: 10.1111/ajt.15898. Epub 2020 May 28. | |
| 32428337 |
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The data analyzed during the current study are available on reasonable request including standards for General Data Protection Regulation and Institutional Review Board approval.
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| Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris | Recruiting | Paris | 75015 | France |
|
| Bichat Hospital, Assistance Publique - Hôpitaux de Paris | Recruiting | Paris | 75018 | France |
|
| Background |
| Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, Dagobert J, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thusen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RB. Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation. Am J Transplant. 2020 Sep;20(9):2305-2317. doi: 10.1111/ajt.16059. Epub 2020 Jun 27. |
| 34922989 | Background | Loupy A, Mengel M, Haas M. Thirty years of the International Banff Classification for Allograft Pathology: the past, present, and future of kidney transplant diagnostics. Kidney Int. 2022 Apr;101(4):678-691. doi: 10.1016/j.kint.2021.11.028. Epub 2021 Dec 17. |
| 38032300 | Background | Naesens M, Roufosse C, Haas M, Lefaucheur C, Mannon RB, Adam BA, Aubert O, Bohmig GA, Callemeyn J, Clahsen-van Groningen M, Cornell LD, Demetris AJ, Drachenberg CB, Einecke G, Fogo AB, Gibson IW, Halloran P, Hidalgo LG, Horsfield C, Huang E, Kikic Z, Kozakowski N, Nankivell B, Rabant M, Randhawa P, Riella LV, Sapir-Pichhadze R, Schinstock C, Solez K, Tambur AR, Thaunat O, Wiebe C, Zielinski D, Colvin R, Loupy A, Mengel M. The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics. Am J Transplant. 2024 Mar;24(3):338-349. doi: 10.1016/j.ajt.2023.10.016. Epub 2023 Oct 28. |