Focal Segmental Glomerulosclerosis

FSGS refers to a pattern of renal injury characterized by segmental glomerular scars that involve some but not all glomeruli; the clinical findings of FSGS largely manifest as proteinuria.

 When the secondary causes of FSGS are eliminated , the remaining patients are considered to have FSGS. The incidence of this disease is increasing, and it now represents up to one-third of cases of nephrotic syndrome in adults and one-half of cases of nephrotic syndrome in African Americans, in whom it is seen more commonly.

 The pathogenesis of FSGS is probably multifactorial. Possible mechanisms include a T cell–mediated circulating permeability factor, TGF-–mediated cellular proliferation and matrix synthesis, and podocyte abnormalities associated with genetic mutations.

Primary focal segmental glomerulosclerosis

Secondary focal segmental glomerulosclerosis
Viruses:  HIV/Hepatitis B/Parvovirus
  Hypertensive nephropathy
  Reflux nephropathy
  Cholesterol emboli

  Drugs: Heroin/analgesics
  Oligomeganephronia
  Renal dysgenesis
  Alport's syndrome
  Sickle cell disease
  Lymphoma
  Radiation nephritis

    Familial podocytopathies
       NPHS1 mutation/nephrin
       NPHS2 mutation/podocin
       TRPC6 mutation/cation channel
       ACTN4 mutation/Actinin
       -Galactosidase A deficiency/Fabry's disease
  N-acetylneuraminic acid hydrolase deficiency/nephrosialidosis

The pathologic changes of FSGS are most prominent in glomeruli located at the corticomedullary junction, so if the renal biopsy specimen is from superficial tissue, the lesions can be missed, which sometimes leads to a misdiagnosis of MCD. In addition to focal and segmental scarring, other variants have been described, including cellular lesions with endocapillary hypercellularity and heavy proteinuria; collapsing glomerulopathy with segmental or global glomerular collapse and a rapid decline in renal function; or the glomerular tip lesion, which seems to have a better prognosis.

FSGS can present with any level of proteinuria, hematuria, hypertension, or renal insufficiency. Nephrotic range proteinuria, African-American race, and renal insufficiency are associated with a poor outcome, with 50% of patients reaching renal failure in 6–8 years. FSGS rarely remits spontaneously, but treatment-induced remission of proteinuria significantly improves prognosis.

Treatment of patients with primary FSGS should include inhibitors of the renin-angiotensin system. Based on retrospective studies, patients with nephrotic range proteinuria can be treated with steroids but respond far less often than patients with MCD. Proteinuria remits in only 20–45% of patients receiving a course of steroids over 6–9 months. Limited evidence suggests that the use of cyclosporine in steroid-responsive patients helps ensure remissions, while other cytotoxic agents confer little added benefit over steroid therapy. Primary FSGS recurs in 25–40% of patients given allografts at end-stage disease, leading to graft loss in half of those cases.

 The treatment of secondary FSGS typically involves treating the underlying cause and controlling proteinuria. There is no role for steroids or other immunosuppressive agents in secondary FSGS.