Kidney nontumor
Primary glomerular diseases
Focal and segmental glomerulosclerosis

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 20 September 2017, last major update April 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Focal and segmental glomerulosclerosis [title]

Cite this page: Sangle, N. Focal and segmental glomerulosclerosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyfsgs.html. Accessed November 25th, 2017.
Definition / general
  • 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, nonselective 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
Treatment
Microscopic (histologic) description
  • Focal and segmental glomerulosclerosis and mesangial sclerosis in lobules that appear to adhere to Bowman 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
Microscopic (histologic) images

Images hosted on PathOut server:

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



Images hosted on other servers:

Focal and segmental glomerulosclerosis

Various images

Positive stains
Immunofluorescence
  • IgM and C3 deposited in focal and segmental manner in the sclerotic segments
Electron microscopy description
  • Epithelial cell detachment from glomerular basement membrane
  • Extensive foot process obliteration (even in nonsclerotic glomeruli), mesangial sclerosis with increased matrix and collapsed glomerular loops
Electron microscopy images

Images hosted on PathOut servers:

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

Cellular variant

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


Microscopic (histologic) description:
  • 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


Microscopic (histologic) images:

Images hosted on other servers:

Various images



Immunofluorescence:
  • Segmental IgM and C3


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