What is the initial management of nephrotic syndrome in pediatric patients?

Initial Management of Nephrotic Syndrome in Pediatric Patients

The initial management of nephrotic syndrome in pediatric patients should consist of oral glucocorticoids (prednisone/prednisolone) at a dose of 60 mg/m²/day (maximum 60 mg) as a single daily dose for 4-6 weeks, followed by 40 mg/m²/day (maximum 40 mg) on alternate days for 4-6 weeks, with a total treatment duration of 8-12 weeks. 1

Diagnostic Approach

Before initiating treatment, consider:

• Empiric glucocorticoid treatment without biopsy is recommended for children without syndromic features or family history 1

• Kidney biopsy and/or genetic testing should be considered in specific cases:

  • Children with syndromic features
  • Family history of nephrotic syndrome
  • Atypical presentation (hypertension, hematuria, renal insufficiency)

• Initial laboratory evaluation:

  • Urinalysis and urine protein-to-creatinine ratio
  • Serum albumin, creatinine, electrolytes, and lipid profile
  • Renal ultrasound to assess kidney size and rule out structural abnormalities 1

Glucocorticoid Treatment Protocol

The 2025 KDIGO guidelines recommend two options for initial treatment 2:

1. 8-week regimen: 4 weeks daily glucocorticoids followed by 4 weeks alternate-day glucocorticoids
2. 12-week regimen: 6 weeks daily glucocorticoids followed by 6 weeks alternate-day glucocorticoids

The specific dosing should be:

• Daily dose: 60 mg/m²/day (maximum 60 mg) as a single morning dose
• Alternate-day dose: 40 mg/m²/day (maximum 40 mg) as a single morning dose

Evidence shows that longer treatment durations (3 months or more) significantly reduce the risk of relapse at 12-24 months compared to shorter durations (2 months) without increasing adverse events 3.

Monitoring During Treatment

While on glucocorticoid therapy, monitor for:

• Proteinuria: Remission is defined as trace/negative protein for at least 3 consecutive days on urine dipstick 2
• Relapse: ≥2+ proteinuria for 3 consecutive days on early morning urine or ≥2+ proteinuria with edema 2
• Steroid-related adverse effects:
  • Blood pressure
  • Weight and height
  • Blood glucose
  • Signs of infection
  • Behavioral changes

Management of Complications

Common complications requiring management:

• Edema: Sodium restriction and judicious use of diuretics
• Infections: Prompt recognition and treatment; consider pneumococcal and annual influenza vaccination 1
• Hypovolemia: Monitor for signs of dehydration, especially during diuretic use
• Thrombosis: Be vigilant for signs of thromboembolism, particularly in severely hypoalbuminemic patients

Management of Relapses

For patients who experience relapses:

• Infrequent relapses: Treat with prednisone 60 mg/m²/day until remission for at least 3 days, followed by alternate-day prednisone (40 mg/m²) for at least 4 weeks 1

• Frequent relapses or steroid-dependent: Consider steroid-sparing agents when steroid-related adverse effects develop 2, 1:

  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Cyclophosphamide (2 mg/kg/day for 8-12 weeks)
  • Mycophenolate mofetil (600-1200 mg/m²/day divided into 2 doses)
  • Levamisole (2.5 mg/kg on alternate days)
  • Rituximab for selected cases

Important Considerations and Pitfalls

• The 2025 KDIGO guidelines recommend against routinely giving daily glucocorticoids during episodes of upper respiratory tract and other infections to reduce relapse risk 2

• Common pitfalls to avoid 1:

  • Inadequate initial steroid duration
  • Rapid steroid tapering
  • Delayed introduction of steroid-sparing agents
  • Overlooking infections
  • Inadequate monitoring of drug toxicity

• Pediatric patients on corticosteroids should be carefully monitored for growth velocity, which may be a more sensitive indicator of systemic corticosteroid exposure than HPA axis function tests 4

• For steroid-resistant nephrotic syndrome, cyclosporine or tacrolimus is recommended as initial second-line therapy 2