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Kidney non-tumor

Primary glomerular diseases

Focal and segmental glomerulosclerosis


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 21 February 2014, last major update April 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
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● A histologic pattern of glomerulosclerosis (affecting some glomeruli, and only part of capillary tuft) associated with heavy proteinuria (> 3.5 g/day) and progressive renal failure
● In normal adults at autopsy, ages 55 or less, glomerulosclerosis affects < 3% of glomeruli (Arch Pathol Lab Med 1989;113:1253)

Primary (idiopathic) form:
● Causes 10% of nephrotic syndrome in children (usually < 5 years old), 20% in adults (20-39 years)
● Associated with hematuria, hypertension, hypercholesterolemia, hypoalbuminemia, non-selective proteinuria and edema
● Rarely is familial
● Overall incidence higher in African-Americans

Secondary forms:
● Causes: congenital heart disease, congenital kidney disease (associated with 19q13 or nephrin alterations), focal proliferative and necrotizing glomerulonephritis-healed, glycogen, heroin addiction, HIV, hypertension, IgA nephropathy, morbid obesity, obstruction, reflux, renal ablation nephropathy, sickle cell disease, storage disease, unilateral renal agenesis
● Similar glomerular lesions as idiopathic forms
● May be due to circulating mediator (proteinuria may recur with allografts in 24 hours, overall in 25-50% of allografts)
● Children have better prognosis than adults, who often progress to renal failure (40-60% overall within 10-20 years)
● Note: minimal change disease, diffuse mesangial hypercellularity and focal segmental glomerulosclerosis may be a continuum of the same disease

Classification
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● Columbia University classification: perihilar, cellular, tip lesion, collapsing and not otherwise specified (Am J Kidney Dis 2004;43:368); correlates with prognosis

Treatment
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● Steroids and cytotoxic therapy in children (Saudi J Kidney Dis Transpl 2010;21:87)
● Gastric bypass surgery may be effective for obesity related disease (Pediatr Nephrol 2009;24:851)
● Also transplant
● Rrituximab may reduce recurrence prior to a second transplant (Transpl Int 2012;25:e62)
● Intensive and prolonged treatment of recurrence may also be effective (Am J Transplant 2009;9:1081)
● Rarely, recurrence post-transplant may spontaneously regress (Saudi J Kidney Dis Transpl 2011;22:1219)

Micro description
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● Focal and segmental glomerulosclerosis and mesangial sclerosis in lobules that appear to adhere to Bowmanís capsule (begins in corticomedullary region), inframembranous hyaline deposits (PAS+, trichrome red, silver negative) and endocapillary foam cells or lipoid droplets in focal glomeruli, initially mild mesangial hypercellularity that becomes hypocellular in advanced lesions
● Focal tubular atrophy with interstitial fibrosis, hyaline thickening of afferent arterioles
● Note: the defining glomerular lesions may not be sampled in needle core biopsy due to their focal nature

Micro images
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Focal and segmental glomerulosclerosis

           
Various images


Enlarged glomeruli with segmental sclerosis NOS on PAS stain


Enlarged glomerulus with a tip lesion on PAS stain #1; #2 Silver stain


Glomerulus with perihilar sclerosis and hyalinosis on PAS #1; #2 on Trichrome


HIV collapsing glomerulopathy on Silver stain


Idiopathic collapsing glomerulopathy on PAS stain

Positive stains
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● High levels of malondialdehyde (Saudi J Kidney Dis Transpl 2010;21:886)

Immunofluorescence
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● IgM and C3 deposited in focal and segmental manner in the sclerotic segments

Electron microscopy description
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● Epithelial cell detachment from glomerular basement membrane
● Extensive foot process obliteration (even in non-sclerotic glomeruli), mesangial sclerosis with increased matrix and collapsed glomerular loops

Electron microscopy images
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Series of images


Foot process effacement in collapsing FSGS #1; #2 in tip variant of FSGS



Cellular variant

General
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● Compared to classic focal segmental glomerulosclerosis (NOS), presents with more severe proteinuria (Kidney Int 2006;70:1783)

Micro description
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● Focal and segmental endocapillary hypercellularity occluding lumens, with foam cells and karryorrhexis, podocyte hypertrophy and hyperplasia; resembles crescents
● May resemble focal proliferative glomerulonephritis, but no glomerular immune deposits are present

Micro images
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Various images

Immunofluorescence
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● Segmental IgM and C3

Electron microscopy description
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● Severe podocyte foot process effacement, occlusion of capillaries by endocapillary hypercellularity including foam cells, and hyaline deposits

End of Kidney non-tumor > Primary glomerular diseases > Focal and segmental glomerulosclerosis

Ref Updated: 4/16/12


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