Focal Segmental Glomerulosclerosis
It is a cause of nephrotic syndrome in children
and adolescents, as well as an important
cause of kidney failure in adults.
• It is also known as "focal glomerular sclerosis"
or "focal nodularglomerulosclerosis”.
• MCD and primary FSGS may have a similar
• Focal segmental glomerulosclerosis
(FSGS) is a major cause of idiopathic
steroid-resistant nephrotic syndrome
(SRNS) and end-stage kidney disease
• FSGS is the most common cause of
acquired chronic renal insufficiency in
1. Collapsing variant→ESRD
2. Glomerular tip lesion variant
3. Cellular variant
4. Perihilar variant
5. Not otherwise specified (NOS) variant. Most common
Classification by Robbins
• 1. In association with other known conditions,
such as HIV infection (HIV Nephropathy) or heroin abuse (Heroin Nephropathy);
• 2. As a secondary event in other forms of GN
(e.g., IgA nephropathy);
• 3. As a maladaptation after nephron loss
• 4. Congenital forms resulting from mutations affecting cytoskeletal proteins
expressed in podocytes (nephrin);
• 5. Primary or Idiopathic
Primary or Idiopathic FSGS
• Primary /Idiopathic FSGS accounts for
approximately 20-30 % of
all cases of the NS. It is becoming an
increasingly common cause of NS in
adults & remains a frequent cause in
FSGS vs MCD
• 1. Hematuria, Hypertension.
• 2. Nonselective proteinuria.
• 3. Poor response to corticosteroids.
• 4. >50% individuals develop ESRF within 10 y.
• 5. Adults in general fare even less well
Pathogenesis - unknown
• MCD may transform to FSGS.
• Distinct clinicopathologic entity from the
• In any case, injury to podocytes is thought
to represent the initiating event of primary
• As with MCD, permeability-increasing factors
produced by lymphocytes (cytokines) have
•The deposition of hyaline
masses in the glomeruli
represents the entrapment of plasma proteins and
lipids in foci of injury where sclerosis develops.
• IgM and complement proteins
commonly seen in the lesion are also believed to
result from nonspecific entrapment in damaged
• The recurrence of proteinuria in some
persons with FSGS who receive renal
allografts, sometimes within 24 hours of
transplantation, supports the idea that
a circulating mediator
is the cause of the damage to podocytes.
The most likely candidate representing the responsible
circulating factor is soluble urokinase-type plasminogen
activator receptor (suPAR). Another possible circulating
factor is Cardiotrophin-like cytokine 1.
• The disease first affects only some of the
glomeruli (Focal) & initially only the
• Eventually all levels of the cortex are affected.
• Lesions occur in some tufts (Segmental)
within a glomerulus.
• The affected glomeruli exihibit:
1.Increased mesangial matrix,
2.Obliterated capillary lumens
3.Deposition of hyaline masses & lipid droplets.
Occasionally , glomeruli are
completely sclerosed with or
without interstitial fibrosis.
• EM shows effacement of foot processes.
Global sclerosis may be found occasionally.
• Collapsing glomerulopathy- Collapse of the
entire glomerular tuft & podocyte hyperplasia.
CG may be associated with HIV inf drug-
induced toxicities. It has a poor prognosis.
• Immunofluorescence microscopy:
• It reveals nonspecific trapping of
immunoglobulins, usually IgM &
complement in the areas of