A novel unbiased method reveals progressive podocyte globotriaosylceramide accumulation and loss with age in females with Fabry disease.


Journal

Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470

Informations de publication

Date de publication:
07 2022
Historique:
received: 04 11 2021
revised: 15 02 2022
accepted: 08 03 2022
pubmed: 29 4 2022
medline: 28 6 2022
entrez: 28 4 2022
Statut: ppublish

Résumé

While females can suffer serious complications of Fabry disease, most studies are limited to males to avoid confounding by mosaicism. Here, we developed a novel unbiased method for quantifying globotriaosylceramide (GL3) inclusion volume in affected podocytes (F+) in females with Fabry disease independent of mosaicism leading to important new observations. All podocytes in male patients with Fabry are F+. The probability of observing random profiles from F+ podocytes without GL3 inclusions (estimation error) was modeled from electron microscopic studies of 99 glomeruli from 40 treatment-naïve males and this model was applied to 28 treatment-naïve females. Also, podocyte structural parameters were compared in 16 age-matched treatment-naïve males and females with classic Fabry disease and 11 normal individuals. A 4

Identifiants

pubmed: 35483528
pii: S0085-2538(22)00341-6
doi: 10.1016/j.kint.2022.03.023
pmc: PMC9233139
mid: NIHMS1801226
pii:
doi:

Substances chimiques

Trihexosylceramides 0
globotriaosylceramide 71965-57-6

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

173-182

Subventions

Organisme : NINDS NIH HHS
ID : U54 NS065768
Pays : United States

Informations de copyright

Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Behzad Najafian (B)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA. Electronic address: najafian@uw.edu.

Aurelio Silvestroni (A)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Alexey Sokolovskiy (A)

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Camilla Tøndel (C)

Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Einar Svarstad (E)

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Bogdan Obrisca (B)

Discipline Nephrology-Fundeni Clinical Institute, Department of Nephrology, Urology, Immunology and Immunology of Transplant, Dermatology, Allergology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Gener Ismail (G)

Discipline Nephrology-Fundeni Clinical Institute, Department of Nephrology, Urology, Immunology and Immunology of Transplant, Dermatology, Allergology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Myrl D Holida (MD)

Medical Genetics and Genomics, Stead Family Department of Pediatrics, University of Iowa Health Care, Iowa City, Iowa, USA.

Michael Mauer (M)

Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

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Classifications MeSH