What is the management of Focal Segmental Glomerulosclerosis (FSGS)?

Management of Focal Segmental Glomerulosclerosis (FSGS)

The management of FSGS should be guided by classification of the disease as primary, genetic, secondary, or undetermined cause, with high-dose glucocorticoids as first-line therapy for primary FSGS and calcineurin inhibitors for steroid-resistant cases. 1

Classification and Diagnostic Approach

• FSGS should be classified into four categories to guide treatment: primary FSGS, genetic FSGS, secondary FSGS, and FSGS of undetermined cause (FSGS-UC) 1
• Primary FSGS is characterized by sudden-onset nephrotic syndrome with diffuse foot process effacement and is potentially responsive to immunosuppressive therapy 2
• Genetic FSGS includes familial, syndromic, and sporadic forms that typically do not respond to immunosuppression 1
• Secondary FSGS can be caused by viral infections, medications, glomerular hyperfiltration, or adaptive changes 1

Diagnostic Evaluation

• Presence of nephrotic syndrome (proteinuria >3.5 g/day AND serum albumin <30 g/L with or without edema) with diffuse foot process effacement suggests primary FSGS 1
• Absence of nephrotic syndrome (proteinuria <3.5 g/day or serum albumin >30 g/L) suggests secondary FSGS or FSGS-UC 1
• Genetic screening should be considered, especially in cases with family history or early onset 2
• All patients should be evaluated for underlying secondary causes before initiating immunosuppressive therapy 1

Treatment Algorithm for Primary FSGS

First-Line Therapy: Glucocorticoids

• High-dose glucocorticoid therapy with prednisone at 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) 1
• Continue high-dose glucocorticoids for at least 4 weeks and until complete remission is achieved, with a maximum duration of 16 weeks 1
• If complete remission is achieved, continue high-dose treatment for several weeks after proteinuria disappears, then taper prednisone by 5 mg every 1-2 weeks to complete a total duration of 6 months 1
• If partial remission occurs within 8-12 weeks, continue high-dose treatment for up to 16 weeks, then taper 1
• Patients who respond to glucocorticoids should receive treatment for at least 6 months total 1

Second-Line Therapy: Calcineurin Inhibitors (CNIs)

• For steroid-resistant FSGS or patients with contraindications to glucocorticoids, CNIs are the preferred alternative therapy 1
• Cyclosporine: 3-5 mg/kg/day in 2 divided doses (target trough level: 100-175 ng/ml) 1
• Tacrolimus: 0.05-0.1 mg/kg/day in 2 divided doses (target trough level: 5-10 ng/ml) 1
• CNI therapy should be continued for a minimum of 12 months in responders to minimize relapse risk 1
• Dose should be titrated based on proteinuria response and serum creatinine; reduce dose if creatinine increases >30% from baseline 1

Alternative Therapies for Resistant Cases

• For frequently relapsing or steroid-dependent cases, options include cyclophosphamide, rituximab, CNIs, or mycophenolic acid analogs 1
• Mycophenolate mofetil has shown success in some high-risk patients who failed previous therapies 3
• Plasmapheresis may provide benefits in some resistant cases, though further evaluation is needed 3

Supportive Therapy

• All patients should receive renin-angiotensin-aldosterone system blockers (ACE inhibitors or ARBs) to reduce proteinuria 3
• Lipid-lowering drugs (statins) for cardiovascular risk reduction 2
• Sodium restriction and diuretics for edema management 3
• Monitor for complications of nephrotic syndrome including thromboembolism, infections, and malnutrition 4

Monitoring and Prognosis

• Proteinuria remission is one of the most important independent predictors of kidney survival 5
• Patients who achieve complete remission have a significantly better prognosis than non-responders 5
• Monitor proteinuria, serum albumin, and kidney function regularly to assess treatment response 1
• CNI therapy requires monitoring of drug levels and kidney function to minimize nephrotoxicity 1

Special Considerations

• Steroid resistance is common in adult FSGS patients and portends worse outcomes 6
• Patients with genetic forms of FSGS typically do not respond to immunosuppression and should receive supportive care only 1
• Secondary FSGS management should focus on treating the underlying cause rather than immunosuppression 1
• The risk of progression to end-stage kidney disease is high in non-responders, with 50% risk within 5 years compared to 10% in those achieving complete remission 5