Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Nov;50(6):405-410.
doi: 10.4132/jptm.2016.09.21. Epub 2016 Oct 16.

Pathogenesis of Focal Segmental Glomerulosclerosis

Beom Jin Lim  1 , Jae Won Yang  2 , Woo Sung Do  1 , Agnes B Fogo  3
Affiliations
Review

Pathogenesis of Focal Segmental Glomerulosclerosis

Beom Jin Lim et al. J Pathol Transl Med. 2016 Nov.

Abstract

Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

Keywords: Focal segmental glomerulosclerosis; Parietal epithelial cells; Permeability factors; Podocytopathy.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
Morphologic variants of focal segmental glomerulosclerosis. (A) Capillary collapse and podocyte hyperplasia are characteristic features of the collapsing variant. (B) In the tip variant, segmental lesion involves the glomerular tuft next to the tubular pole. (C) The perihilar variant is diagnosed when sclerosis or hyalinosis are present in perihilar lesion in more than half of the sclerotic glomeruli.
See this image and copyright information in PMC

References

    1. D’Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43:368–82. - PubMed
    1. Weiss MA, Daquioag E, Margolin EG, Pollak VE. Nephrotic syndrome, progressive irreversible renal failure, and glomerular “collapse”: a new clinicopathologic entity? Am J Kidney Dis. 1986;7:20–8. - PubMed
    1. Moudgil A, Nast CC, Bagga A, et al. Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy. Kidney Int. 2001;59:2126–33. - PubMed
    1. Markowitz GS, Appel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol. 2001;12:1164–72. - PubMed
    1. Markowitz GS, Nasr SH, Stokes MB, D’Agati VD. Treatment with IFN-α, -β, or -γ is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010;5:607–15. - PMC - PubMed

LinkOut - more resources