Treatment Approach for Nephrotic Syndrome vs Nephritic Syndrome in Pediatric Patients
Critical Distinction: These Are Different Diseases Requiring Completely Different Management
Nephrotic syndrome and nephritic syndrome are fundamentally different glomerular diseases with opposing treatment strategies—nephrotic syndrome is treated primarily with corticosteroids, while nephritic syndrome (acute post-infectious glomerulonephritis) is managed supportively without immunosuppression.
Nephrotic Syndrome Treatment
Initial Presentation (<12 years, no syndromic features)
Start oral prednisone 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) as a single morning dose for 4-6 weeks, followed by alternate-day prednisone 40 mg/m² for 2-5 months. 1, 2
- Total treatment duration should be 8-12 weeks minimum (either 4 weeks daily + 4 weeks alternate-day OR 6 weeks daily + 6 weeks alternate-day) 1
- Longer initial courses up to 6 months reduce relapse risk 1, 2
- Approximately 80-94% of children will achieve remission with this regimen 3, 4
Children >12 Years or With Syndromic Features
Perform kidney biopsy and/or genetic testing before initiating corticosteroids and refer to specialty center. 1
- Children <1 year likely have genetic causes and should not receive standard corticosteroid regimens 2
- Syndromic features include skeletal abnormalities, neurodevelopmental delays, deafness, genital ambiguity, or facial dysmorphisms 1
Relapse Management
For infrequent relapses: Treat with prednisone 60 mg/m²/day until 3 consecutive days of remission, then switch to alternate-day prednisone 40 mg/m² for 4 weeks. 1, 2
- Relapse defined as ≥3+ protein on dipstick for 3 consecutive days 2
- Remission defined as urine protein <1+ on dipstick for 3 consecutive days 2
Frequent Relapses or Steroid-Dependent Disease
For children with frequent relapses who develop serious glucocorticoid toxicity or all children with steroid-dependent nephrotic syndrome, prescribe glucocorticoid-sparing agents rather than continuing corticosteroids alone. 1
The 2025 KDIGO guidelines eliminate the distinction between "first-line" and "alternative" agents 1:
- For frequently relapsing disease: Cyclophosphamide (2 mg/kg/day for 8-12 weeks) or levamisole (2.5 mg/kg alternate days) are preferable 1
- For steroid-dependent disease: Mycophenolate mofetil, rituximab, calcineurin inhibitors (cyclosporine/tacrolimus), or cyclophosphamide are preferable 1
- Patients should be in remission with glucocorticoids before starting these agents, with glucocorticoids continued for 2 weeks after initiation 1
Steroid-Resistant Nephrotic Syndrome
Use cyclosporine or tacrolimus as initial second-line therapy for steroid-resistant disease. 1
- Rituximab may achieve remission in approximately 30% of children with calcineurin inhibitor-resistant disease 1
Important Practice Changes from 2025 Guidelines
Do NOT routinely give daily glucocorticoids during upper respiratory tract infections to prevent relapses in children with frequently relapsing or steroid-dependent disease. 1
- The PREDNOS2 study showed no benefit of prophylactic steroids during infections 1
- Exception: May consider 3 extra doses of low-dose prednisone (0.5 mg/kg/day) in children already on alternate-day therapy with history of repeated infection-associated relapses 1
Nephritic Syndrome Treatment
Acute Post-Infectious Glomerulonephritis (Classic Nephritic Syndrome)
Nephritic syndrome requires supportive care only—do NOT use corticosteroids or immunosuppression.
The management is fundamentally different from nephrotic syndrome:
- Fluid and sodium restriction for edema and hypertension
- Antihypertensive therapy (typically loop diuretics, calcium channel blockers, or ACE inhibitors) for blood pressure control
- Monitor for complications: Acute kidney injury, severe hypertension, pulmonary edema, hyperkalemia
- Antibiotics only if active streptococcal infection is documented (penicillin for 10 days)
- Self-limited disease: Most children recover completely within 2-4 weeks without immunosuppression
Key Distinguishing Features
| Feature | Nephrotic Syndrome | Nephritic Syndrome |
|---|---|---|
| Proteinuria | Massive (>40 mg/m²/hr) | Mild-moderate |
| Hematuria | Microscopic or absent | Gross hematuria common |
| Edema | Severe, generalized | Mild, periorbital |
| Hypertension | Uncommon | Common |
| Complement (C3) | Normal | Low |
| Treatment | Corticosteroids | Supportive only |
Critical Pitfalls to Avoid
- Never treat nephritic syndrome with corticosteroids—this is a post-infectious process requiring supportive care only
- Never discontinue steroids abruptly in nephrotic syndrome—increases relapse risk 2, 5
- Never use standard corticosteroid regimens in children <1 year without genetic testing—they likely have genetic forms 2
- Never continue corticosteroids alone in steroid-dependent disease—glucocorticoid-sparing agents are mandatory 1
- Never assume FSGS on biopsy means steroid resistance—19% of white children with FSGS respond to corticosteroids 3