J Pathol Transl Med.  2016 Nov;50(6):405-410. 10.4132/jptm.2016.09.21.

Pathogenesis of Focal Segmental Glomerulosclerosis

• Lim BJ
• Yang JW
• Do WS
• Fogo AB

• KMID: 2361987
• DOI: http://doi.org/10.4132/jptm.2016.09.21

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.

Keyword

Focal segmental glomerulosclerosis; Podocytopathy; Permeability factors; Parietal epithelial cells

MeSH Terms

Actin Cytoskeleton
Age of Onset
Capillaries
Diaphragm
Epithelial Cells
Foot
Glomerulosclerosis, Focal Segmental*
Nephrosis, Lipoid
Pathology
Permeability
Podocytes
Rabeprazole
Sclerosis
Wills

Figure

• 

  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.

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