Deep learning-based segmentation and quantification of podocyte foot process morphology suggests differential patterns of foot process effacement across kidney pathologies.

Journal: Kidney international
PMID:

Abstract

Morphological alterations at the kidney filtration barrier increase intrinsic capillary wall permeability resulting in albuminuria. However, automated, quantitative assessment of these morphological changes has not been possible with electron or light microscopy. Here we present a deep learning-based approach for segmentation and quantitative analysis of foot processes in images acquired with confocal and super-resolution fluorescence microscopy. Our method, Automatic Morphological Analysis of Podocytes (AMAP), accurately segments podocyte foot processes and quantifies their morphology. AMAP applied to a set of kidney diseases in patient biopsies and a mouse model of focal segmental glomerulosclerosis allowed for accurate and comprehensive quantification of various morphometric features. With the use of AMAP, detailed morphology of podocyte foot process effacement was found to differ between categories of kidney pathologies, showed detailed variability between diverse patients with the same clinical diagnosis, and correlated with levels of proteinuria. AMAP could potentially complement other readouts such as various omics, standard histologic/electron microscopy and blood/urine assays for future personalized diagnosis and treatment of kidney disease. Thus, our novel finding could have implications to afford an understanding of early phases of kidney disease progression and may provide supplemental information in precision diagnostics.

Authors

  • David Unnersjö-Jess
    Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany; MedTechLabs, Karolinska University Hospital, Solna, Sweden; Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden; Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden. Electronic address: daviduj@kth.se.
  • Linus Butt
    Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. Electronic address: Linus.Butt@uk-koeln.de.
  • Martin Höhne
    Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
  • German Sergei
    Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
  • Arash Fatehi
    Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
  • Anna Witasp
    Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
  • Annika Wernerson
    Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
  • Jaakko Patrakka
    KI/AZ Integrated CardioMetabolic Center, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Peter F Hoyer
    Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany.
  • Hans Blom
    MedTechLabs, Karolinska University Hospital, Solna, Sweden; Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.
  • Bernhard Schermer
    Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
  • Katarzyna Bozek
    Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Thomas Benzing
    Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.