FSGS

An increasing cause of end-stage renal disease is the pathological lesion focal and segmental glomerulosclerosis (FSGS). FSGS is characterized by proteinuria and frequently nephrotic syndrome with ensuing renal failure. The etiology remains unknown in the majority of individuals.

The idiopathic form of FSGS is most common; however, secondary forms of FSGS do exist.

There is a form of FSGS that is fulminant that frequently recurs after renal transplantation with an estimated frequency of approximately 30%, suggesting that the pathogenesis is not solely a result of intrinsic kidney disease.

Recently, hereditary forms of the disease were recognized as well as those associated with other congenital syndromes. Known genetic causes of the hereditary form of this disease have been suggested to account for upwards of 18% of cases.

Synopsis

Localized anywhere, defined by obliteration of capillary lumen and increased matrix, extensive foot process effacement by EM.

Early lesions

 small peripheral foci of segmental glomerulosclerosis
 well-defined peripheral segmental sclerosis
 glomerular intracapillary foam cells
 prominence of overlying visceral epithelial cells.
 surrounding mild interstitial fibrosis
 mild enlargment of sclerosed glomeruli

Advanced lesions

 diffuse glomerulosclerosis
 moderate to severe renal interstitial fibrosis
 renal tubular atrophy
 increased mesangial matrix
 obliteration of glomerular capillaries

Etiology

 idiopathic FSGS
 WT1-associated FSGS

• WT1 splice site mutation (14646409)

 TRPC6-associated FSGS

• germline mutations in TRPC6 cause focal segmental glomerulosclerosis

 OXPHOS system anomalies (mitochondrial cytopathy) (16328667)

Susceptibility loci

 9q31-q32 (12840782)

See also

 glomerulosclerosis
 hereditary FSGS
 podocyte slit diaphragm

References

 D’Agati VD. Podocyte injury in focal segmental glomerulosclerosis: Lessons from animal models (a play in five acts). Kidney Int. 2008 Feb;73(4):399-406. PMID: 17989648

 Daskalakis N, Winn MP. Focal and segmental glomerulosclerosis. Cell Mol Life Sci. 2006 Nov;63(21):2506-11. PMID: 16952054

 Kriz W. TRPC6 - a new podocyte gene involved in focal segmental glomerulosclerosis. Trends Mol Med. 2005 Dec;11(12):527-30. PMID: 16290061