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Basic Research
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Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis

Brandon Ginley, Kuang-Yu Jen, Seung Seok Han, Luís Rodrigues, Sanjay Jain, Agnes B. Fogo, Jonathan Zuckerman, Vighnesh Walavalkar, Jeffrey C. Miecznikowski, Yumeng Wen, Felicia Yen, Donghwan Yun, Kyung Chul Moon, Avi Rosenberg, Chirag Parikh and Pinaki Sarder
JASN February 2021, ASN.2020050652; DOI: https://doi.org/10.1681/ASN.2020050652
Brandon Ginley
1Departments of Pathology and Anatomical Sciences, University at Buffalo – The State University of New York, Buffalo, New York
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Kuang-Yu Jen
2Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California
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Seung Seok Han
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Luís Rodrigues
4University Clinic of Nephrology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
5Nephrology Unit, Coimbra Hospital and University Center, Coimbra, Portugal
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Sanjay Jain
6Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Agnes B. Fogo
7Departments of Pathology, Microbiology, and Immunology, and Medicine, Vanderbilt University, Nashville, Tennessee
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Jonathan Zuckerman
8Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
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Vighnesh Walavalkar
9Department of Pathology, University of California at San Francisco, San Francisco, California
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Jeffrey C. Miecznikowski
10Department of Biostatistics, University at Buffalo – The State University of New York, Buffalo, New York
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Yumeng Wen
11Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Felicia Yen
2Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California
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Donghwan Yun
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Kyung Chul Moon
12Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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Avi Rosenberg
13Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Chirag Parikh
11Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Pinaki Sarder
1Departments of Pathology and Anatomical Sciences, University at Buffalo – The State University of New York, Buffalo, New York
14Department of Biomedical Engineering, University at Buffalo – The State University of New York, Buffalo, New York
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Significance Statement

Reliable, digital, automated detection of interstitial fibrosis and tubular atrophy (IFTA) has not yet been developed. Machine learning (ML) can reproduce the renal pathologist’s visual assessment of IFTA and glomerulosclerosis. Well-trained ML methods not only showed similar agreement to that seen among renal pathologists for the assessment of IFTA and glomerulosclerosis, but also equivalent statistical association with patient outcome. These methods can help expedite research on very large digital archives of renal biopsy specimens, and may also benefit clinical practice by acting as a stand-in reading for pathology scenarios where renal expertise is limited or unavailable.

Abstract

Background Interstitial fibrosis, tubular atrophy (IFTA), and glomerulosclerosis are indicators of irrecoverable kidney injury. Modern machine learning (ML) tools have enabled robust, automated identification of image structures that can be comparable with analysis by human experts. ML algorithms were developed and tested for the ability to replicate the detection and quantification of IFTA and glomerulosclerosis that renal pathologists perform.

Methods A renal pathologist annotated renal biopsy specimens from 116 whole-slide images (WSIs) for IFTA and glomerulosclerosis. A total of 79 WSIs were used for training different configurations of a convolutional neural network (CNN), and 17 and 20 WSIs were used as internal and external testing cases, respectively. The best model was compared against the input of four renal pathologists on 20 new testing slides. Further, for 87 testing biopsy specimens, IFTA and glomerulosclerosis measurements made by pathologists and the CNN were correlated to patient outcome using classic statistical tools.

Results The best average performance across all image classes came from a DeepLab version 2 network trained at 40× magnification. IFTA and glomerulosclerosis percentages derived from this CNN achieved high levels of agreement with four renal pathologists. The pathologist- and CNN-based analyses of IFTA and glomerulosclerosis showed statistically significant and equivalent correlation with all patient-outcome variables.

Conclusions ML algorithms can be trained to replicate the IFTA and glomerulosclerosis assessment performed by renal pathologists. This suggests computational methods may be able to provide a standardized approach to evaluate the extent of chronic kidney injury in situations in which renal-pathologist time is restricted or unavailable.

  • interstitial fibrosis
  • tubular atrophy
  • glomerulosclerosis
  • prognostication
  • convolutional neural network
  • whole slide segmentation
  • diabetes
  • transplant
  • eGFR
  • Copyright © 2021 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 32 (3)
Journal of the American Society of Nephrology
Vol. 32, Issue 3
March 2021
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Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis
Brandon Ginley, Kuang-Yu Jen, Seung Seok Han, Luís Rodrigues, Sanjay Jain, Agnes B. Fogo, Jonathan Zuckerman, Vighnesh Walavalkar, Jeffrey C. Miecznikowski, Yumeng Wen, Felicia Yen, Donghwan Yun, Kyung Chul Moon, Avi Rosenberg, Chirag Parikh, Pinaki Sarder
JASN Feb 2021, ASN.2020050652; DOI: 10.1681/ASN.2020050652

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Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis
Brandon Ginley, Kuang-Yu Jen, Seung Seok Han, Luís Rodrigues, Sanjay Jain, Agnes B. Fogo, Jonathan Zuckerman, Vighnesh Walavalkar, Jeffrey C. Miecznikowski, Yumeng Wen, Felicia Yen, Donghwan Yun, Kyung Chul Moon, Avi Rosenberg, Chirag Parikh, Pinaki Sarder
JASN Feb 2021, ASN.2020050652; DOI: 10.1681/ASN.2020050652
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Keywords

  • interstitial fibrosis
  • tubular atrophy
  • glomerulosclerosis
  • prognostication
  • convolutional neural network
  • whole slide segmentation
  • diabetes
  • transplant
  • eGFR

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