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Continuous indices to assess the phenotypic spectrum of kidney transplant rejection

Author

Listed:
  • Thibaut Vaulet

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation)

  • Priyanka Koshy

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    KU Leuven, Department of Imaging and Pathology, Translational Cell and Tissue Research
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Karolien Wellekens

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Olivier Aubert

    (Necker Enfants Malades Institute (INEM), Université Paris Cité, Inserm UMR1151
    Université Paris Cité, Department of Kidney and Metabolic Diseases, Transplantation and Clinical Immunology, Necker Hospital, Assistance Publique - Hôpitaux de Paris)

  • Charlotte Bottomley

    (Imperial College, Department of Immunology and Inflammation)

  • Jasper Callemeyn

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Evert Cleenders

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    KU Leuven, Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care)

  • Maarten Coemans

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    KU Leuven, Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care)

  • Lynn Cornell

    (Department of Pathology & Laboratory Medicine and Department of Medicine at the University of Calgary)

  • Aiko P. J. de Vries

    (Leiden University Medical Center, Division of Nephrology, Department of Medicine
    Leiden University Medical Center, Leiden Transplant Center)

  • Gillian Divard

    (Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, INSERM U970 PARCC)

  • Marie-Paule Emonds

    (Belgian Red Cross-Flanders, Histocompatibility and Immunogenetics Laboratory)

  • Sandrine Florquin

    (Dept. of Pathology, Amsterdam UMC, University of Amsterdam
    Amsterdam Institute for Infection and Immunology)

  • Mark Haas

    (Cedars-Sinai Medical Center, Department of Pathology and Laboratory Medicine)

  • Philip F. Halloran

    (University of Alberta, Department of Medicine)

  • Jesper Kers

    (Leiden University Medical Center, Division of Nephrology, Department of Medicine
    Leiden University Medical Center, Leiden Transplant Center
    University of Amsterdam, Department of Pathology, Amsterdam UMC
    Leiden University Medical Center, Department of Pathology, Leiden Transplant Center)

  • Dirk Kuypers

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Thangamani Muthukumar

    (Weill Cornell Medicine, Division of Nephrology and Hypertension)

  • Angelica Pagliazzi

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Steven Salvatore

    (Weill Cornell Medicine, Department of Pathology and Laboratory Medicine)

  • Olivier Thaunat

    (Univ. Lyon, CIRI, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon
    Edouard Herriot Hospital, Department of Transplantation, Nephrology, and Clinical Immunology, Hospices Civils de Lyon)

  • Surya V. Seshan

    (Weill Cornell Medicine, Department of Pathology and Laboratory Medicine)

  • Elisabet Van Loon

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Thomas Vanhoutte

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

  • Georg A. Böhmig

    (Medical University of Vienna, Division of Nephrology and Dialysis, Department of Medicine III)

  • Friedrich A. von Samson-Himmelstjerna

    (University Hospital Schleswig-Holstein—Campus Kiel, Department of Nephrology and Hypertension)

  • Michelle Willicombe

    (Imperial College, Department of Immunology and Inflammation)

  • Aravind Cherukuri

    (University of Pittsburgh, Thomas E. Starzl Transplantation Institute)

  • Alexandre Loupy

    (Paris Institute for Transplantation and Organ Regeneration, Université Paris Cité, INSERM U970 PARCC)

  • Candice Roufosse

    (Imperial College, Department of Immunology and Inflammation)

  • Maarten Naesens

    (KU Leuven, Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven, Department of Nephrology and Renal Transplantation)

Abstract

The Banff classification for kidney transplant pathology dichotomizes the rejection continuum into distinct diagnostic categories, introducing artificial cutoff points and threshold effects. To better reflect the underlying disease spectrum, in this cohort study of 19,500 biopsies from 8873 patients across 10 centers worldwide, we developed two indices for quantifying antibody-mediated rejection/microvascular inflammation and T-cell-mediated rejection/tubulointerstitial inflammation from histological lesion scores and calculated indices for overall activity and chronicity. These indices demonstrate excellent discrimination for the main diagnostic categories of rejection (AUCs from 0.95 to 0.99), with consistent performance across derivation and validation datasets. These indices strictly confine intermediate phenotypes to low index values and are associated to graft failure even within the diagnostic categories, thus reflecting the underlying rejection continuum. In this work, we demonstrate that four continuous indices provide implementable and interpretable global evaluation of kidney transplant histology that align with the continuous nature of the rejection process regardless of the underlying disease cause.

Suggested Citation

  • Thibaut Vaulet & Priyanka Koshy & Karolien Wellekens & Olivier Aubert & Charlotte Bottomley & Jasper Callemeyn & Evert Cleenders & Maarten Coemans & Lynn Cornell & Aiko P. J. de Vries & Gillian Divard, 2025. "Continuous indices to assess the phenotypic spectrum of kidney transplant rejection," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65153-9
    DOI: 10.1038/s41467-025-65153-9
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