What is the treatment for nephrotic syndrome?

Treatment of Nephrotic Syndrome

The treatment of nephrotic syndrome requires both supportive care and disease-specific therapy, with high-dose oral glucocorticoids (1mg/kg/day) for 4-16 weeks being the first-line treatment for primary forms in adults, while supportive measures include diuretics, ACE inhibitors/ARBs, and statins. 1

Diagnosis and Classification

Nephrotic syndrome is characterized by:

• Heavy proteinuria (>3.5g/24h)
• Hypoalbuminemia (<3.0g/dL)
• Edema
• Hyperlipidemia 1, 2

Classification:

• Congenital/infantile
• Primary/idiopathic (most common in adults: focal segmental glomerulosclerosis and membranous nephropathy)
• Secondary (due to diabetes, lupus, infections, etc.) 1, 3

Treatment Approach

Supportive Care

1. Edema Management:

   • Sodium restriction
   • Fluid restriction
   • Loop diuretics (furosemide 0.5-2 mg/kg per dose) 1
   • Ambulatory management preferred when possible 1

2. Proteinuria Reduction:

   • ACE inhibitors or ARBs 1

3. Hyperlipidemia Management:

   • Statins with target LDL-cholesterol of 100 mg/dl 1

4. Thrombosis Prevention:

   • Anticoagulation in high-risk patients 1
   • Note: Routine prophylactic anticoagulation is not universally recommended 3

Disease-Specific Therapy

Primary/Idiopathic Nephrotic Syndrome

1. First-line Treatment:

   • High-dose oral glucocorticoids (prednisone/prednisolone at 1 mg/kg/day)
   • Continue for 4-16 weeks or until complete remission 1

2. Steroid-Resistant Cases:

   • Calcineurin inhibitors 1, 4
   • Consider calcineurin inhibitors as first-line for patients with contraindications to steroids 1

3. Other Immunosuppressive Options:

   • Mycophenolate mofetil
   • Rituximab (anti-CD20 monoclonal antibodies)
   • Cyclophosphamide 4

Specific Disease Treatments

• Lupus Nephritis (Class III/IV):

  • Initial: Mycophenolate mofetil or cyclophosphamide plus glucocorticoids
  • Maintenance: MMF or azathioprine with low-dose prednisone for at least 3 years 1

• Post-infectious glomerulonephritis:

  • Antimicrobial therapy for underlying infection 1

• IgA nephropathy:

  • ACE inhibitors/ARBs
  • Consider corticosteroids for persistent proteinuria 1

• ANCA-associated vasculitis:

  • Cyclophosphamide or rituximab plus corticosteroids 1

Monitoring and Follow-up

Regular monitoring should include:

• Body weight
• Blood pressure
• Renal function
• Proteinuria
• Serum albumin
• Urinary sediment 1

Visit frequency:

• Every 2-4 weeks during first 2-4 months after diagnosis or flare 1

Response assessment:

• Complete response: Return of serum creatinine to baseline and decline in UPCR to <500-700 mg/g
• Partial response: Stabilization or improvement of serum creatinine but UPCR still >500-700 mg/g 1

Special Considerations for Pediatric Patients

• Corticosteroids are first-line treatment for minimal change disease in children 1, 4
• Cyclophosphamide may be considered for steroid-resistant cases 1
• Monitor growth velocity in children on prolonged corticosteroid treatment 1, 5
• Consider growth hormone substitution in children with growth issues 1

Complications to Monitor and Prevent

• Venous thromboembolism
• Infections (especially in immunosuppressed patients)
• Acute kidney injury
• Hyperlipidemia 1, 2, 3

Common Pitfalls to Avoid

1. Treating based on serum albumin levels alone rather than clinical indicators of hypovolemia
2. Overreliance on immunosuppression for genetic forms of nephrotic syndrome
3. Fluid overload due to excessive fluid administration
4. Inadequate thromboprophylaxis in high-risk patients
5. Failure to monitor for and prevent infections in immunosuppressed patients 1
6. Delaying genetic testing in suspected congenital/infantile cases 1
7. Not considering potential side effects of corticosteroids, particularly in pediatric and geriatric populations 5

When to Consider Renal Biopsy

• Adults with nephrotic syndrome without clear etiology
• Worsening kidney function
• Non-responsiveness to treatment
• Relapse
• To assess histologic transition or changes in chronicity/activity indices 1, 3