Focal & segmental glomerulosclerosis


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Focal & segmental glomerulosclerosis

  1. 1. Focal & Segmental Glomerulosclerosis Focal & Segmental Glomerulosclerosis Lecture 41
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. • The affected glomeruli exihibit: 1.Increased mesangial matrix, 2.Obliterated capillary lumens 3.Deposition of hyaline masses & lipid droplets.
  13. 13. Morphology Global Sclerosis: Occasionally , glomeruli are completely sclerosed with or without interstitial fibrosis.
  14. 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. 15. Morphology • Immunofluorescence microscopy: • It reveals nonspecific trapping of immunoglobulins, usually IgM & complement in the areas of hyalinosis.