• Characterized by glomerular scarring from podocyte injury and depletion4
  • Patients typically present with subnephrotic to nephrotic ranges of proteinuria, hypertension, microscopic hematuria, and renal insufficiency
  • Approximately 20-25% of adult patients undergoing biopsy evaluation for idiopathic glomerulonephritis (GN) are diagnosed with primary (idiopathic) FSGS
  • Approximately 35% of adult patients undergoing biopsy evaluation for idiopathic nephrotic syndrome are diagnosed with FSGS, making it the most common lesion found5
  • The remaining patients have secondary FSGS from genetic factors, drugs, infection, or other structural/functional adaptations
  • Most common primary glomerular disease leading to ESRD
  • Incidence rate estimated to be about 2.7 patients/million on average in the United States
  • Higher male dominance
    • 1.5:1 male-to-female ratio
    • Can occur at any age
  • Most common in African Americans, followed by Hispanics and Caucasians4
  • Prognosis varies depending on levels of proteinuria:
    • Non-nephrotic levels — <15% progress to ESRD over 10 years
    • Nephrotic levels — ≤50% progress to ESRD over 5-10 years
    • Massive levels — ESRD within 2-3 years5
  • Histologically, FSGS can be observed by 5 types of scarring patterns:
    • Cellular variant — overabundance of cells within the glomerulus, impinging on the blood vessels
    • Tip lesion variant — scarring appears at the tip or pole of the glomerulus (best overall outcomes)
    • Perihilar variant — scarring appears where blood vessels enter and exit the glomerulus
    • Collapsing variant — scarring affects the entire glomerulus leading to a collapsed appearance (lowest overall outcomes)
    • Not otherwise specified (NOS) variant – must exclude other variants; defined by blocked glomerular capillaries form extracellular matrix accumulations6

ESRD: end-stage renal disease

Recommendations are based on the KDIGO Clinical
Practice Guideline for Glomerulonephritis

  • Treatment aimed towards remission of proteinuria to slow/control progression of ESRD
    • Prognosis goals: proteinuria reduction, complete or partial remission of nephrotic syndrome, and stable or improved renal function
  • Options are based on degree and persistence of nephrotic-range proteinuria and kidney function
  • Initial therapy upon diagnosis should consist of daily or alternating-day doses of corticosteroids if FSGS presents with nephrotic syndrome
    • 4-16 weeks of treatment until remission
  • CNIs are prescribed for first line of defense if patients cannot tolerate/are resistant to corticosteroids or have contraindications
    • Cyclosporine is recommended, but tacrolimus is mentioned as a potential option for intolerant patients
  • If a patient is resistant to corticosteroids and intolerant to CNIs, a combination therapy of MMF and high-dose dexamethasone is recommended
  • As of 2012, the KDIGO guidelines list the following therapies as potential treatment options, but they are not recommended this agent:
    • Alkylating agents (cyclophosphamide/chlorambucil)
    • Monoclonal antibodies (rituximab)10

Alternative option not listed in 2012 KDIGO Guidelines

  • The product is an FDA approved treatment option11

CNI: calcineurin inhibitor; ESRD: end-stage renal disease; MMF: mycophenolate mofetil.

Treatment Options
Immunosuppressive Therapy
  • Prednisone
  • Dexamethasone
  • Cytotoxic Agents10
  • Chlorambucil (Leukeran®)
  • Cyclophosphamide (Cytoxan®)
  • Monoclonal Antibodies10
  • Rituximab (Rituxan®)
  • Calcineurin Inhibitors10
  • Cyclosporine (Gengraf®)
  • Tacrolimus (Prograf®)
  • Immunosuppressive Agents10
  • Mycophenolate mofetil (CellCept®)
  • The Product®11*

    *FDA approved, but not enough contemporaneous data for KDIGO to make a use recommendation