What is the treatment for Focal Segmental Glomerulosclerosis (FSGN)?

Treatment for Focal Segmental Glomerulosclerosis (FSGS)

High-dose glucocorticoids are the first-line therapy for primary FSGS with nephrotic syndrome, while calcineurin inhibitors (CNIs) should be used in patients with contraindications to steroids. 1

Initial Treatment Approach

Conservative Management

• All patients with FSGS should receive supportive therapy with:
  • ACE inhibitors or ARBs titrated to maximally tolerated dose to reduce proteinuria 1
  • Blood pressure control targeting systolic BP <120 mmHg using standardized office measurements 1
  • Dietary sodium restriction to <2.0 g/day (<90 mmol/day) 1
  • Lifestyle modifications including weight normalization, smoking cessation, and regular exercise 1
  • Diuretics for edema management as needed 1
  • Consider statin therapy for hyperlipidemia, especially in patients with other cardiovascular risk factors 1

Immunosuppressive Therapy for Primary FSGS

• Immunosuppressive therapy should only be considered for idiopathic FSGS with nephrotic syndrome 1
• Secondary forms of FSGS (adaptive/hyperfiltration) should be treated with conservative management only 2

First-Line Therapy: Glucocorticoids

• Dosing: Prednisone/prednisolone 1 mg/kg/day (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg) 1
• Duration: Continue high-dose glucocorticoids for at least 4 weeks and up to 16 weeks as tolerated or until complete remission 1
• Tapering: After achieving remission, taper by 5 mg every 1-2 weeks to complete a total treatment duration of 6 months 1
• Monitoring: Patients who respond typically show some degree of proteinuria reduction before 16 weeks 1
• If no response after 4-8 weeks or significant toxicity develops, consider switching to alternative therapy 1

Second-Line Therapy: Calcineurin Inhibitors (CNIs)

• Consider as first-line therapy in patients with contraindications to glucocorticoids (uncontrolled diabetes, psychiatric conditions, severe osteoporosis) 1
• Options:
  • 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
• Duration: Continue for at least 4-6 months before determining resistance; if effective, maintain for at least 12 months total 1
• Tapering: After achieving remission, continue at target dose for at least 2 months, then slowly taper over 6-12 months 1

Treatment of Steroid-Resistant FSGS

• For patients who fail to respond to glucocorticoids, a trial of CNIs is recommended 1, 3
• If no response to CNIs after 6 months (defined as <50% reduction in baseline proteinuria), consider alternative therapies 1, 3
• Alternative options with limited evidence include:
  • Mycophenolate mofetil in selected high-risk patients 3
  • Plasmapheresis may provide benefits in some resistant cases 3
  • Combination therapy approaches 4

Monitoring and Follow-up

• Monitor laboratory values frequently in patients on ACEi/ARB therapy 1
• Counsel patients to temporarily discontinue ACEi/ARB and diuretics when at risk for volume depletion 1
• For patients on CNIs, monitor renal function closely and reduce dose if serum creatinine increases >30% from baseline 1
• If serum creatinine does not improve after dose reduction, consider discontinuing CNI 1

Common Pitfalls and Caveats

• Distinguish between primary and secondary FSGS before initiating immunosuppression, as secondary forms typically don't respond to immunosuppressive therapy 1, 2
• Do not start ACEi/ARB in patients with abrupt onset of nephrotic syndrome as these drugs can cause acute kidney injury, especially in minimal change disease 1
• Consider using potassium-wasting diuretics and/or potassium-binding agents to manage hyperkalemia when using RAS blockers 1
• Relapse is common after CNI withdrawal, suggesting these agents may have hemodynamic effects rather than treating the underlying disease process 1
• Treatment response is a stronger predictor of renal survival than histologic findings 1, 3