Focal Segmental Glomerulosclerosis (FSGS)

Overview
  • Focal Segmental Glomerulosclerosis (FSGS) is a disease defined principally by a unique histopathology that primarily manifests clinically as nephrotic syndrome. It is most importantly characterized by a histopathology of focal and segmental sclerosis of glomeruli
Morphology
  • Light Microscopy:
    • FSGS is characterized by "Sclerosis" of Glomeruli, meaning the deposition of an undifferentiated hyaline substance within the glomerulus. The sclerosis of glomeruli displays a unique focal and segmental pattern which gives FSGS its namesake. Focal sclerosis refers to the observation that only a certain subset of glomeruli are affected, traditionally, glomeruli near the corticomedullary border . Segmental sclerosis refers to the fact that only a segment of each individual glomerulus appears sclerosed.
  • Immunofluorescence:
    • Deposition of IgM and complement in sclerosed regions of glomeruli.
  • Electron Microscopy:
    • Effacement of podocyte foot processes along with substantial detachement of podocytes from the glomerular basement membrane.
Etiology
  • Primary Disease
    • The etiology of primary FSGS is highly unclear. Whatever the initial insult, it appears that a localized area of the glomerular barrier is rendered leaky in a certain subset of glomeruli. This leads to a localized deposition of plasma proteins that initiates a 'segment' of sclerosis within that glomerulus. Deposition of IgM and complement in areas of sclerosis appears to be due trapping of these proteins within previously damaged glomeruli; thus, these are not thought to be the primary initiators of pathology
    • Nephrotic syndrome then develops due to the reduced selectivity of glomerular filtration.
  • Secondary Disease
    • FSGS can appear secondary to a variety of infectious, pharmacological, or genetic insults. Infectious etiologies include HIV while FSGS is often observed in the end-stage of compensatory glomerulopathy.
Clinical Consequences
  • FSGS can occur in both children and adults, primarily manifesting as nephrotic syndrome (i.e. proteinuria, hypoalbuminemia , generalized edema, hyperlipidemia). Because a wide variety of plasma proteins are lost in the urine FSGS is said to involve a "nonselective proteinuria". Disease is typically progressive and tends toward chronic renal failure in many cases. In children, this disease must be distinguished from minimal change disease as it does not respond nearly as well to corticosteroid therapy and is more prone to serious progression.