BanffNET, a Deep Learning System for Comprehensive Histological Lesion Quantification in Kidney Transplant Biopsies
Abstract
Abstract Accurate, reproducible interpretation of kidney allograft biopsies is critical for the diagnosis of graft injury and for informing prognosis and clinical management. The international Banff classification is a consensus diagnostic system based on semiquantitative histological lesion scoring according to either lesion extent or severity in kidney transplant biopsies. However, pathologist scoring is limited by interobserver variability, constrained scalability, and the inherent nature of the scoring system itself. Here we present BanffNET, a weakly supervised, probabilistic deep learning framework that combines self-supervised feature extraction with a novel Bayesian multiple-instance learning framework to predict (continuously) the full spectrum of Banff lesion scores directly from whole-slide images (WSIs). Using lesion-specific aggregation functions tailored to localized (modeling severity) and diffuse histological lesions (modeling extent), BanffNET generates interpretable, patch-level probability maps and calibrated slide-level scores. BanffNET’s performance was assessed relative to consensus, biological correlates of rejection and clinical outcome, demonstrating superior consistency, transportability and generalization. Trained on 7,533 WSIs from three cohorts, BanffNET demonstrates consistent performance on 12,687 WSIs across five external validation cohorts, matching or surpassing individual expert pathologists across lesion assessments. BanffNET scores align more closely than pathologist Banff scores with molecular profiles of rejection, offering an objective, transparent, biologically grounded framework for computational pathology with relevance beyond kidney transplantation.
Authors 47
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Pathology, Systems Pathology Research Group, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Ospedale di Parma · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Medicine and Surgery, Nephrology Unit, Parma University Hospital, Parma, Italy
Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Pathology, Systems Pathology Research Group, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, Netherlands
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Pathology, Systems Pathology Research Group, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Center, Radboud University, Nijmegen, Netherlands
-
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Pathology, RWTH Aachen University Hospital, Aachen, Germany
-
David L. Hoelscher Aachen Center of Excellence in Nephrology Department of Nephrology and Hypertension Rheumatology and Immunology (Medical Clinic II) Medical Faculty Institute for Pathology
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Center of Excellence in Nephrology, University Hospitals Aachen, Cologne, Dusseldorf
Department of Nephrology and Hypertension, Rheumatology and Immunology (Medical Clinic II), Medical Faculty RWTH Aachen, Aachen, Germany
Institute for Pathology, RWTH Aachen University Hospital, Aachen, Germany
-
Anja Muehlfeld Aachen Center of Excellence in Nephrology Department of Nephrology and Hypertension Rheumatology and Immunology (Medical Clinic II) Medical Faculty
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Center of Excellence in Nephrology, University Hospitals Aachen, Cologne, Dusseldorf
Department of Nephrology and Hypertension, Rheumatology and Immunology (Medical Clinic II), Medical Faculty RWTH Aachen, Aachen, Germany
-
Affiliation as printed
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
-
Affiliation as printed
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
-
Affiliation as printed
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
-
Affiliation as printed
Department of Medicine, University of Alberta, Edmonton, Canada
-
Leiden University Medical Center
Affiliation as printed
Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Soufian Meziyerh Aachen Division of Nephrology Department Internal Medicine, and Leiden Transplant Center Leiden Transplant Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Division of Nephrology, Department Internal Medicine, and Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Jouke Dijkstra Aachen Division of Image Processing Department of Radiology, Leiden University Medical Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Radboud University Medical Center
Affiliation as printed
Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands
-
Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Center, Radboud University, Nijmegen, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Amsterdam University Medical Centers · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Amsterdam University Medical Center, University of Amsterdam and VU University, Amsterdam, Netherlands
-
Amsterdam University Medical Centers · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Internal Medicine, Division of Nephrology, Amsterdam University Medical Center, University of Amsterdam and VU University, Amsterdam, Netherlands
-
Affiliation as printed
Cell Systems and Drug Safety, Leiden Academic Center for Drug Research, Leiden University, Leiden, Netherlands
-
Affiliation as printed
Cell Systems and Drug Safety, Leiden Academic Center for Drug Research, Leiden University, Leiden, Netherlands
-
Affiliation as printed
Cell Systems and Drug Safety, Leiden Academic Center for Drug Research, Leiden University, Leiden, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Nephrology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Affiliation as printed
Department of Medicine and Surgery, Nephrology Unit, Parma University Hospital, Parma, Italy
-
Affiliation as printed
Department of Medicine and Surgery, Nephrology Unit, Parma University Hospital, Parma, Italy
-
Affiliation as printed
Department of Medicine and Surgery, Nephrology Unit, Parma University Hospital, Parma, Italy
-
Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
-
Azienda Ospedaliero-Universitaria di Modena
Affiliation as printed
Nephrology, Dialysis and Kidney Transplant Unit, University Hospital of Modena, Modena, Italy
-
Azienda Ospedaliero-Universitaria di Modena
Affiliation as printed
Nephrology, Dialysis and Kidney Transplant Unit, University Hospital of Modena, Modena, Italy
-
Affiliation as printed
Department of Histopathology, African Medical Center of Excellence Hospital, Abuja, Nigeria
-
Affiliation as printed
Department of Medicine and Surgery, Nephrology Unit, Parma University Hospital, Parma, Italy
-
Affiliation as printed
Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, Netherlands
-
Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Center for Infection and Molecular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
-
Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Department of Pathology, University Hospitals Leuven, Leuven, Belgium
-
Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
-
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Pathology, RWTH Aachen University Hospital, Aachen, Germany
-
Onno YK Teng Aachen Center of Expertise for Lupus Division of Nephrology Department Internal Medicine, and Leiden Transplant Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Center of expertise for Lupus-, Vasculitis and Complement-mediated Systemic Autoimmune Disease (LuVaCs), Leiden University Medical Center, Leiden University, Leiden, Netherlands
Division of Nephrology, Department Internal Medicine, and Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
-
Aiko Pj de Vries Aachen Division of Nephrology Department Internal Medicine, and Leiden Transplant Center Leiden Transplant Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Division of Nephrology, Department Internal Medicine, and Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
Leiden Transplant Center, Leiden University Medical Center, Leiden University, Leiden, Netherlands
-
Leiden University · Leiden University Medical Center · Erasmus MC · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
Department of Pathology, Erasmus Medical Center, Rotterdam, Netherlands
Department of Pathology, Systems Pathology Research Group, Leiden University Medical Center, Leiden University, Leiden, Netherlands
Cited by 2 stored of 2
2 results
No patents citing this paper on Lens.org (checked 2026-10-06).