Continuous indices to assess the phenotypic spectrum of kidney transplant rejection

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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-11-26
DOI
https://doi.org/10.1038/s41467-025-65153-9
Citations
5
Primary Topic
Renal Transplantation Outcomes and Treatments
Type
article
Field-Weighted Citation Impact
9.93

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Continuous indices to assess the phenotypic spectrum of kidney transplant rejection

Aravind Cherukuri, Olivier Aubert, Michelle Willicombe, Thangamani Muthukumar et al.
5 citations
Nature Communications
Renal Transplantation Outcomes and Treatments
9.93
article

Continuous indices to assess the phenotypic spectrum of kidney transplant rejection

Aravind Cherukuri, Olivier Aubert, Michelle Willicombe, Thangamani Muthukumar, Elisabet Van Loon, Karolien Wellekens, Jesper Kers, Marie‐Paule Emonds, Maarten Naesens, Sandrine Florquin, Jasper Callemeyn, Gillian Divard, Evert Cleenders, Maarten Coemans, Angelica Pagliazzi, Candice Roufosse, Dirk Kuypers, Alexandre Loupy, Mark Haas, Priyanka Koshy, Olivier Thaunat, Friedrich Alexander von Samson‐Himmelstjerna, Surya V. Seshan, Georg A. Böhmig, Philip F. Halloran, Steven Salvatore, Thomas Vanhoutte, Aiko P. J. de Vries, Thibaut Vaulet, Lynn D. Cornell, Charlotte Bottomley
article en
5 citations

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.

Nature CommunicationsVol. 16(1)
Université Claude Bernard Lyon 1 (FR), École Normale Supérieure de Lyon (FR), Cedars-Sinai Medical Center (US), Centre National de la Recherche Scientifique (FR), University of Alberta (CA), Inserm (FR), University of Calgary (CA), University of Pittsburgh (US), Université Paris Cité (FR), Cornell University (US), Leiden University Medical Center (NL), Institut Necker Enfants Malades (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), University Hospital Schleswig-Holstein (DE), Paris Cardiovascular Research Center (FR), Amsterdam University Medical Centers (NL), Centre International de Recherche en Infectiologie (FR), Weill Cornell Medicine (US), Imperial College London (GB), Medical University of Vienna (AT), University of Amsterdam (NL), University of Lübeck (DE), KU Leuven (BE)
National Institute for Health and Care Research, Fonds Wetenschappelijk Onderzoek, KU Leuven, Vlaamse regering, NIHR Imperial Biomedical Research Centre
Openalex Percentile: Top 2%
Renal Transplantation Outcomes and Treatments
9.93
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.