• Marta Sablik, Aurélie Sannier, Marc Raynaud, Valentin Goutaudier, Gillian Divard, Brad C Astor, Patricia Weng, Jodi Smith, Rouba Garro, Bradley A Warady, Rima S Zahr, Katherine Twombley, Vikas R Dharnidharka, Raja S Dandamudi, Marc Fila, Edmund Huang, Anne-Laure Sellier-Leclerc, Burkhard Tönshoff, Marion Rabant, Jérôme Verine, Arnaud Del Bello, Thierry Berney, Olivia Boyer, Rusan Ali Catar, Richard Danger, Magali Giral, Daniel Yoo, François R Girardin, Alaa Alsadi, Pierre-Antoine Gourraud, Emmanuel Morelon, 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, and Alexandre Loupy.
• From Université Paris Cité, INSERM Unité 970, Paris Institute for Transplantation and Organ Regeneration (M.S., A.S., M. Raynaud, V.G., G.D., D.Y., J.H., C. Legendre, O.A., C. Lefaucheur, A.L.), the Department of Pathology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) (A.S.), the Kidney Transplant Department (G.D., C. Lefaucheur) and the Department of Pathology (J. Verine), Saint-Louis Hospital, AP-HP, the Department of Pathology, Necker Hospital, AP-HP (M. Rabant), the Division of Pediatric Nephrology, Necker Hospital, AP-HP, Université Paris Cité (O. Boyer), the Department of Kidney Transplantation, Necker Hospital, AP-HP (M.T., C. Legendre, D.A., O.A., A.L.), and the Division of Pediatric Nephrology, Robert Debré Hospital, AP-HP (J.H.), Paris, the Departments of Pediatric Nephrology (M.F.) and Nephrology (M.L.Q.), Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier, the Pediatric Nephrology Department, Hôpital Universitaire Mère-Enfant, Hospices Civils de Lyon (HCL) (A.-L.S.-L.), and the Department of Transplantation, Edouard Herriot University Hospital, HCL, University of Lyon I (E.M.), Lyon, the Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse (A.B., N.K.), Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, Unité Mixte de Recherche 1064, Institute of Urology-Nephrology Transplantation of the University Hospital of Nantes, Nantes (R.D., M.G., P.-A.G., S.B.), and the Departments of Pathology (B.C.) and Nephrology, Transplantation, Dialysis, and Apheresis (L.C.), CHU Bordeaux, Bordeaux - all in France; the Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health (B.C.A.), and the Department of Pathology, University of Wisconsin (A.A., W.Z.) - both in Madison; Pediatric Nephrology, David Geffen School of Medicine at UCLA, UCLA Mattel Children's Hospital (P.W.), and Cedars-Sinai Comprehensive Transplant Center (E.H.) - both in Los Angeles; the Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle (J.S.); the Division of Pediatric Nephrology, Emory University School of Medicine, Children's Pediatric Institute, Atlanta (R.G.); the Division of Pediatric Nephrology, University of Kansas City, Children's Mercy Hospital, Kansas City, MO (B.A.W.); the Division of Pediatric Nephrology and Hypertension, University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis (R.S.Z.); the Acute Dialysis Units, Pediatric Kidney Transplant, Medical University of South Carolina, Charleston (K.T.); the Division of Pediatric Nephrology, Hypertension, and Apheresis, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis (V.R.D., R.S.D.); the Department of Pediatrics, Robert Wood Johnson Medical School at Rutgers University, New Brunswick, NJ (V.R.D.); the Department of Pediatrics I, University Children Hospital Heidelberg, Heidelberg (B.T.), and the Department of Nephrology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Berlin Institute of Health, Berlin (R.A.C., K.B.) - both in Germany; the Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals (T.B.), and the Division of Transplantation Immunology, University Hospital of Geneva (J. Villard), Geneva, and the Division of Clinical Pharmacology, Department of Medicine, and the Department of Laboratory Medicine and Pathology, Lausanne University Hospital, Faculty of Medicine, University of Lausanne, Lausanne (F.R.G.) - all in Switzerland; and the Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital, Barcelona (O. Bestard).
• N. Engl. J. Med. 2024 Oct 24.

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionsMicrovascular 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.).Copyright © 2024 Massachusetts Medical Society.

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