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

Jess, David Unnersjö (author)
KTH,Biofysik,Science for Life Laboratory, SciLifeLab,Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.;Karolinska Univ Hosp, MedTechLabs, Solna, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, Stockholm, Sweden.
Butt, Linus (author)
Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.;Univ Hosp Cologne, Dept Internal Med 2, Kerpener Str 62, D-50937 Cologne, Germany.
Hoehne, Martin (author)
Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.
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Sergei, German (author)
Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.
Fatehi, Arash (author)
Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.
Witasp, Anna (author)
Karolinska Institutet
Wernerson, Annika (author)
Karolinska Institutet
Patrakka, Jaakko (author)
Karolinska Institutet
Hoyer, Peter F. (author)
Univ Duisburg Essen, Pediat Nephrol, Pediat 2, Essen, Germany.
Blom, Hans, 1968- (author)
KTH,Science for Life Laboratory, SciLifeLab,Biofysik,Karolinska Univ Hosp, MedTechLabs, Solna, Sweden.
Schermer, Bernhard (author)
Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.
Bozek, Katarzyna (author)
Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.;Ctr Mol Med Cologne CMMC, Robert Koch Str 21, D-50931 Cologne, Germany.
Benzing, Thomas (author)
Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany.;Univ Hosp Cologne, Cologne, Germany.;Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.;Univ Cologne, Cologne Excellence Cluster Cellular Stress Respons, Cologne, Germany.
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 (creator_code:org_t)
Elsevier BV, 2023
2023
English.
In: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 103:6, s. 1120-1130
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  • Journal article (peer-reviewed)
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  • 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.

Keyword

artificial intelligence
kidney pathology
podocyte

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