Molecular Landscape of Microvascular Inflammation in Kidney Allografts

Comprehensive Multiscale Characterization of the Molecular Landscape of Microvascular Inflammation in Kidney Allografts

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:

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.

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