• 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
Corticosteroids10 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