Molecular Landscape of Microvascular Inflammation in Kidney Allografts

NCT ID: NCT06342128

Last Updated: 2025-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

600 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-01-01

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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:

1. To decipher the spatial immune-molecular landscape of microvascular inflammation in kidney allografts.
2. To compare the characteristics of this landscape in different clinical scenarios.

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.

Conditions

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Kidney Rejection Transplant

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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No intervention

No intervention

Intervention Type OTHER

Eligibility Criteria

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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

* Inadequate biopsy according to the Banff classification
* Missing data for Banff lesion scores, donor-specific antibody status, C4d staining
* Biopsies showing histological signs of ischemia-reperfusion
* Combined transplantation and kidney transplantation after a non-kidney solid organ transplantation
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Paris Translational Research Center for Organ Transplantation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris

Paris, , France

Site Status RECRUITING

Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris

Paris, , France

Site Status RECRUITING

Bichat Hospital, Assistance Publique - Hôpitaux de Paris

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Alexandre Loupy, MD PhD

Role: CONTACT

+33612491082

Catherine Tritscher

Role: CONTACT

+33153988000

Facility Contacts

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Carmen Lefaucheur, MD PhD

Role: primary

Alexandre Loupy, MD PhD

Role: primary

+33612491082

Aurélie Sannier, MD PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 32463180 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32428337 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34922989 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38032300 (View on PubMed)

Other Identifiers

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MVI_Kidney_001

Identifier Type: -

Identifier Source: org_study_id

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