What is the initial treatment for a patient with an exacerbation of nephrotic syndrome?

Initial Treatment for Nephrotic Syndrome Exacerbation

The initial treatment for a patient with an exacerbation of nephrotic syndrome should be high-dose corticosteroids, specifically prednisone or prednisolone at a daily single dose of 1 mg/kg (maximum 80 mg) or an alternate-day dose of 2 mg/kg (maximum 120 mg). 1

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis of nephrotic syndrome by verifying:

• Proteinuria >3.5g/day
• Hypoalbuminemia
• Edema
• Hyperlipidemia

Treatment Algorithm

First-Line Therapy: Corticosteroids

1. Initial dosing:

   • Adults: Prednisone/prednisolone 1 mg/kg/day (maximum 80 mg) as a single daily dose OR 2 mg/kg on alternate days (maximum 120 mg) 2, 1
   • Children: Prednisone/prednisolone 60 mg/m²/day (maximum 60 mg) as a single daily dose 1

2. Duration:

   • Continue high-dose corticosteroids for a minimum of 4 weeks
   • Extend treatment up to a maximum of 16 weeks as tolerated, or until complete remission is achieved 2, 1
   • After achieving complete remission, taper steroids slowly over 6 months 2

Alternative First-Line Options (for patients with contraindications to steroids)

For patients with contraindications to high-dose corticosteroids (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis):

• Consider calcineurin inhibitors (CNIs) such as cyclosporine (3-5 mg/kg/day in divided doses) or tacrolimus 2, 1

Supportive Management

Implement these measures concurrently with immunosuppressive therapy:

1. Blood pressure control:

   • ACE inhibitors or ARBs for hypertension and proteinuria reduction 2
   • Target BP <130/80 mmHg

2. Edema management:

   • Sodium restriction (<2.0 g/day) 2
   • Diuretics (loop diuretics for significant edema)
   • Consider potassium-wasting diuretics if hyperkalemia is present 2

3. Hyperlipidemia management:

   • Consider statin therapy, particularly for patients with other cardiovascular risk factors 2

4. Thrombosis prevention:

   • Evaluate risk of venous thromboembolism
   • Consider prophylactic anticoagulation for high-risk patients, particularly those with membranous nephropathy 1

Monitoring Response

1. Monitor proteinuria regularly:

   • Target reduction: 25% by 3 months, 50% by 6 months 1
   • Goal: <0.5-0.7 g/24h by 12 months 1

2. Monitor for complications:

   • Renal function (serum creatinine, eGFR)
   • Electrolyte abnormalities
   • Steroid-related adverse effects
   • Infections

Special Considerations

For Minimal Change Disease (MCD)

• Most responsive to corticosteroids
• Consider cyclophosphamide for frequent relapses 2

For Focal Segmental Glomerulosclerosis (FSGS)

• May require longer course of corticosteroids
• For steroid-resistant FSGS, consider cyclosporine at 3-5 mg/kg/day in divided doses for at least 4-6 months 2

For Membranous Nephropathy (MN)

• Consider a 6-month course of alternating monthly cycles of corticosteroids and oral alkylating agents 2
• Cyclophosphamide preferred over chlorambucil 2

Common Pitfalls to Avoid

1. Inadequate initial steroid duration: Ensure minimum 4 weeks of high-dose treatment 1
2. Rapid steroid tapering: Taper slowly over 6 months after remission to reduce relapse risk 1
3. Delayed recognition of steroid resistance: Consider alternative therapy if no improvement after 16 weeks of steroids
4. Overlooking infections: Monitor for and promptly treat infections
5. Inadequate monitoring of drug toxicity: Regular monitoring of blood counts, renal function, and drug levels for specific agents

Patient Instructions

1. Hold ACEi/ARB and diuretics during episodes of volume depletion (vomiting, diarrhea) 2
2. Restrict dietary sodium to <2.0 g/day 2
3. Regular monitoring of weight and edema
4. Report signs of infection promptly
5. Adhere to medication regimen and follow-up appointments