Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome characterized by scarring of the glomeruli. It commonly affects children and adults and can lead to end-stage kidney disease. The pathology involves focal and segmental scarring within the glomeruli along with effacement of foot processes. While the exact cause is unknown, it is believed to involve injury to filtering structures in the kidney (podocytes) potentially from circulating permeability factors.

1. Focal & Segmental Glomerulosclerosis
Focal
& Segmental
Glomerulosclerosis
Lecture 41

2. 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
cause.

3. FSGS
• Focal segmental glomerulosclerosis
(FSGS) is a major cause of idiopathic
steroid-resistant nephrotic syndrome
(SRNS) and end-stage kidney disease
(ESKD).
• FSGS is the most common cause of
acquired chronic renal insufficiency in
children.

4. Pathologic variants
1. Collapsing variant→ESRD
2. Glomerular tip lesion variant
3. Cellular variant
4. Perihilar variant
5. Not otherwise specified (NOS) variant. Most common

5. 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
disease

6. 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
children.

7. 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
than children.

8. Pathogenesis - unknown
• MCD may transform to FSGS.
• Distinct clinicopathologic entity from the
outset (beginning).
• In any case, injury to podocytes is thought
to represent the initiating event of primary
FSGS.
• As with MCD, permeability-increasing factors
produced by lymphocytes (cytokines) have
been proposed.

9. •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
glomeruli.

10. • 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.

11. Morphology
• The disease first affects only some of the
glomeruli (Focal) & initially only the
juxtamedullary glomeruli.
• Eventually all levels of the cortex are affected.
• Lesions occur in some tufts (Segmental)
within a glomerulus.

12. • The affected glomeruli exihibit:
1.Increased mesangial matrix,
2.Obliterated capillary lumens
3.Deposition of hyaline masses & lipid droplets.

13. Morphology
Global Sclerosis:
Occasionally , glomeruli are
completely sclerosed with or
without interstitial fibrosis.

14. Morphology
• 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.

15. Morphology
• Immunofluorescence microscopy:
• It reveals nonspecific trapping of
immunoglobulins, usually IgM &
complement in the areas of
hyalinosis.