What is the initial treatment to reduce proteinuria in a patient with nephrotic syndrome?

Initial Treatment for Nephrotic Syndrome

The initial treatment for a patient with nephrotic syndrome should be steroids (prednisone or prednisolone), which is the most effective first-line therapy to reduce proteinuria. 1

Rationale for Steroid Therapy

Corticosteroids remain the mainstay of treatment for nephrotic syndrome based on strong guideline recommendations. The KDIGO practice guideline specifically recommends:

• 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) 2
• Initial high-dose corticosteroids should be given for a minimum of 4 weeks and continued up to a maximum of 16 weeks as tolerated, or until complete remission is achieved 2
• After achieving complete remission, steroids should be tapered slowly over a period of 6 months 2

Treatment Algorithm

1. Initial Assessment:

   • Confirm nephrotic syndrome diagnosis (proteinuria >3.5g/24h, hypoalbuminemia, edema, hyperlipidemia)
   • Determine if primary (idiopathic) or secondary nephrotic syndrome
   • Perform kidney biopsy if indicated to determine underlying pathology

2. First-Line Treatment:

   • Start prednisone/prednisolone 1 mg/kg/day (maximum 80 mg) as a single daily dose 1
   • Continue high-dose steroids for minimum 4 weeks if remission achieved
   • May continue up to 16 weeks if remission not yet achieved 2
   • Monitor for response: Goal is reduction in proteinuria by at least 25% by 3 months, 50% by 6 months 2

3. Alternative First-Line Options (for patients with contraindications to high-dose steroids):

   • Consider calcineurin inhibitors (CNIs) such as cyclosporine (3-4 mg/kg/day) or tacrolimus 2
   • This is particularly important for patients with uncontrolled diabetes, psychiatric conditions, or severe osteoporosis 2

Supporting Evidence

The recommendation for steroids as initial therapy is supported by multiple guidelines and studies. The FDA label for prednisone specifically lists its indication "to induce a diuresis or remission of proteinuria in the nephrotic syndrome" 3.

A Cochrane systematic review found that adult patients treated with cyclosporine plus low-dose prednisone were significantly more likely to achieve remission compared to prednisone alone (RR 8.85,95% CI 1.22 to 63.92) 4. However, steroids remain the first-line therapy due to their established efficacy and the potential nephrotoxicity of long-term calcineurin inhibitor use.

Special Considerations

• Histological subtype matters: Response to steroids varies by underlying pathology. For example, in focal segmental glomerulosclerosis (FSGS), corticosteroids are recommended only in idiopathic FSGS associated with nephrotic syndrome 2

• Conservative measures: While initiating steroid therapy, also implement:

  • Blood pressure control with ACE inhibitors or ARBs
  • Sodium restriction
  • Diuretics for edema management
  • Statins for hyperlipidemia 2

• Monitoring: Regular assessment of:

  • Proteinuria (target <0.5-0.7 g/24h by 12 months)
  • Renal function
  • Steroid-related adverse effects

Common Pitfalls to Avoid

• Inadequate initial treatment duration: Ensure minimum 4 weeks of high-dose treatment 1
• Rapid steroid tapering: Taper slowly over 6 months after remission to reduce relapse risk 1
• Overlooking contraindications to steroids: In patients with significant contraindications, consider CNIs as first-line therapy 2
• Neglecting supportive care: Always include blood pressure control, edema management, and lipid control alongside immunosuppressive therapy

The answer is B. Steroid therapy.