Accumulation of Globotriaosylceramide in Podocytes in Fabry Nephropathy Is Associated with Progressive Podocyte Loss.

Journal of the American Society of Nephrology : JASN
Behzad NajafianMichael Mauer

Abstract

In males with classic Fabry disease, the processes leading to the frequent outcome of ESKD are poorly understood. Defects in the gene encoding α-galactosidase A lead to accumulation of globotriaosylceramide (GL3) in various cell types. In the glomerular podocytes, accumulation of GL3 progresses with age. Of concern, podocytes are relatively resistant to enzyme replacement therapy and are poorly replicating, with little ability to compensate for cell loss. In this study of 55 males (mean age 27 years) with classic Fabry disease genotype and/or phenotype, we performed unbiased quantitative morphometric electron microscopic studies of biopsied kidney samples from patients and seven living transplant donors (to serve as controls). We extracted clinical information from medical records and clinical trial databases. Podocyte GL3 volume fraction (proportion of podocyte cytoplasm occupied by GL3) increased with age up to about age 27, suggesting that increasing podocyte GL3 volume fraction beyond a threshold may compromise survival of these cells. GL3 accumulation was associated with podocyte injury and loss, as evidenced by increased foot process width (a generally accepted structural marker of podocyte stress and injury) and with dec...Continue Reading

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Citations

Sep 24, 2020·Genes·Tina LevstekKatarina Trebusak Podkrajsek
Aug 29, 2020·Aging·Natalya V KaverinaStuart J Shankland
Jan 13, 2021·Cell and Tissue Research·Catherine Meyer-Schwesinger
Jan 31, 2021·Cells·So-Young KimEun Young Lee
Apr 20, 2020·The American Journal of Pathology·Marica GilibertiLoreto Gesualdo
Mar 27, 2021·Clinical and Experimental Nephrology·Sandro Feriozzi, Paula Rozenfeld
Apr 1, 2021·Canadian Journal of Kidney Health and Disease·Cassiano Augusto Braga SilvaFellype Carvalho Barreto
May 1, 2021·Journal of Clinical Medicine·Clara Carnicer-CáceresGuillem Pintos-Morell
Jun 22, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Malte Lenders, Eva Brand
Aug 4, 2021·Molecular Genetics and Metabolism·Jakob M DommMichael L West
Aug 18, 2021·Molecular Genetics and Metabolism Reports·Daniel G BichetKathy Nicholls

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