Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies

Zhengzi Yi, Fadi Salem, Madhav C. Menon, Karen Keung, Caixia Xi, Sebastian Hultin, M. Rizwan Haroon Al Rasheed, Li Li, Fei Su, Zeguo Sun, Chengguo Wei, Weiqing Huang, Samuel Fredericks, Qisheng Lin, Khadija Banu, Germaine Wong, Natasha M. Rogers, Samira Farouk, Paolo Cravedi, Meena ShingdeR. Neal Smith, Ivy A. Rosales, Philip J. O'Connell, Robert B. Colvin, Barbara Murphy, Weijia Zhang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning–based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid– Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalKidney International
Volume101
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • deep learning
  • graft survival
  • kidney transplantation
  • renal pathology

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