Microvascular Inflammation of Kidney Allografts and Clinical Outcomes
Marta Sablik, Aurélie Sannier, Marc Raynaud, Valentin Goutaudier, Gillian Divard, Brad C. Astor, Patricia L. Weng, Jodi M. Smith, Rouba Garro, Bradley A. Warady, Rima S. Zahr, Katherine Twombley, Vikas R. Dharnidharka, Raja Dandamudi, Marc Fila, Edmund Huang, Anne‐Laure Sellier‐Leclerc, Burkhard Tönshoff, Marion Rabant, Jérôme Verine, Arnaud Del Bello, Thierry Berney, Olivia Boyer, Rusan Catar, Richard Danger, Magali Giral, Daniel Yoo, François Girardin, Alaa Alsadi, Pierre‐Antoine Gourraud, Emmanuel Morélon, Moglie Le Quintrec, Mélanie Try, Jean Villard, Weixiong Zhong, Oriol Bestard, Klemens Budde, Bertrand Chauveau, Lionel Couzi, Sophie Brouard, Julien Hogan, Christophe Legendre, Dany Anglicheau, Olivier Aubert, Nassim Kamar, Carmen Lefaucheur, Alexandre Loupy
Abstract
BACKGROUND: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear. METHODS: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression. RESULTS: A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation. CONCLUSIONS: Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts. (Funded by OrganX. ClinicalTrials.gov number, NCT06496269.).