Kidney nontumor
Glomerular disease
Focal segmental glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis-general
Author: Nikhil Sangle, M.D.
Topic Completed: 2 April 2012
Minor changes: 10 October 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Focal and segmental glomerulosclerosis [title]
Table of Contents
Definition / general | Classification | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Immunofluorescence description | Electron microscopy description | Electron microscopy images | Cellular variantCite this page: Sangle N. Focal segmental glomerulosclerosis-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneyfsgs.html. Accessed January 17th, 2021.
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
- Columbia University classification: perihilar, cellular, tip lesion, collapsing and not otherwise specified (Am J Kidney Dis 2004;43:368); correlates with prognosis
Treatment
- 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
- Rituximab 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 posttransplant may spontaneously regress (Saudi J Kidney Dis Transpl 2011;22:1219)
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
- High levels of malondialdehyde (Saudi J Kidney Dis Transpl 2010;21:886)
Immunofluorescence description
- 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
