Initial Management of Pediatric Nephrotic Syndrome
Begin oral prednisone at 60 mg/m²/day (maximum 60 mg) as a single morning dose for 6 weeks, followed by 40 mg/m² on alternate days for another 6 weeks, then taper over 4 weeks for a total 16-week course. 1, 2, 3
Diagnostic Confirmation Before Treatment
Before initiating corticosteroids, verify the diagnostic triad:
- Nephrotic-range proteinuria: UPCR ≥2000 mg/g (≥200 mg/mmol) or ≥3+ on urine dipstick 1, 3
- Hypoalbuminemia: Serum albumin ≤2.5 g/dL (not <3 g/dL as suggested in newer guidelines, as this lacks validation) 1
- Edema: Clinical finding of fluid retention 1, 4
Critical age consideration: Children younger than 1 year likely have genetic nephrotic syndrome and should NOT receive standard corticosteroid therapy without genetic testing and specialized evaluation. 2, 3
Initial Corticosteroid Regimen
The evidence strongly supports a 12-16 week initial course over shorter 8-week regimens:
Daily Phase (Weeks 1-6)
- Prednisone 60 mg/m²/day (or 2 mg/kg/day) as single morning dose 1, 2, 3, 5
- Maximum daily dose: 60 mg 1, 2, 3, 5
- Continue until remission achieved (typically 4-6 weeks in 85-90% of patients) 4, 6, 7
Alternate-Day Phase (Weeks 7-12)
- Prednisone 40 mg/m² (or 1.5 mg/kg) on alternate days 1, 2, 3, 5
- Maximum alternate-day dose: 40 mg 2, 3
Tapering Phase (Weeks 13-16)
- Reduce by 10 mg/m² per week until reaching 5 mg on alternate days 1
- Total treatment duration: 16 weeks 1, 3
Evidence nuance: While KDIGO 2021 suggests 8-12 weeks may be acceptable 1, the Ibadan consensus and multiple studies demonstrate that longer initial courses (12-16 weeks) significantly reduce relapse rates without substantially increasing steroid toxicity. 1, 8, 9 The 16-week regimen is preferred in real-world practice.
Monitoring During Initial Treatment
Weekly Assessment
- Urine dipstick for protein (first morning void preferred) 3
- Blood pressure measurement 3
- Weight and edema assessment 3
- Monitor for steroid side effects (mood changes, hyperglycemia, hypertension) 10
Laboratory Monitoring
- Serum albumin at 4-6 weeks 3
- UPCR when dipstick becomes trace/negative to confirm remission 3
- Electrolytes if using diuretics 1
Definition of Remission
Remission: Urine protein trace or negative on dipstick for 3 consecutive days, or UPCR <200 mg/g (<20 mg/mmol) 1, 2, 3
Most children (80-94%) achieve remission within 4-6 weeks of daily prednisone. 3, 6, 7
Supportive Management
Edema Management
- Salt restriction (no added salt diet) 4, 8, 9
- Fluid restriction only if serum sodium <125 mEq/L 4
- Diuretics (furosemide 1-2 mg/kg/day) reserved for severe, symptomatic edema after confirming adequate intravascular volume 1, 4, 8, 9
Critical pitfall: Avoid aggressive diuresis in hypovolemic patients—assess for signs of intravascular depletion (tachycardia, prolonged capillary refill, oliguria) before administering diuretics. 1
Albumin Infusions
- NOT routinely indicated based on albumin levels alone 1
- Reserve for clinical hypovolemia: oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension, or abdominal discomfort 1
- Dose: 0.5-1 g/kg of 25% albumin over 2-4 hours if needed 1
Infection Prevention
- Pneumococcal vaccination if not previously immunized 3, 9
- Consider prophylactic antibiotics only in high-risk situations (not routine) 8, 9
- Educate families about increased infection risk, particularly pneumococcal peritonitis and sepsis 4, 7
Thromboembolism Prophylaxis
- Consider anticoagulation if serum albumin <2.0 g/dL, especially with additional risk factors 3
- Avoid central venous lines when possible due to high thrombosis risk 1
Additional Supportive Measures
- Calcium and vitamin D supplementation during corticosteroid therapy 10, 4, 8
- ACE inhibitor or ARB for blood pressure control and proteinuria reduction (though less critical during initial episode) 1, 3
- Dietary modifications: Normal protein intake (not restricted), reduce saturated fats and simple carbohydrates 4
When Kidney Biopsy is NOT Needed
Do NOT perform kidney biopsy in children aged 1-10 years with typical presentation who respond to corticosteroids. 3, 4
When Kidney Biopsy IS Indicated
Perform kidney biopsy if any of the following are present:
- Age <1 year 2, 4
- Age >10 years 4
- Macroscopic hematuria 4
- Hypertension 4
- Low C3 complement levels 4
- Persistent renal dysfunction 4
- Steroid resistance (no remission after 6-8 weeks of daily prednisone) 1, 3
Expected Outcomes and Relapse Patterns
- 80-94% of children achieve remission with initial corticosteroid therapy 3, 6, 7
- Approximately 80% will experience at least one relapse 2, 3
- 50% will develop frequent relapses or steroid dependence 2, 5
- 30% experience only one episode and are cured after initial treatment 8
Relapse definition: ≥2+ proteinuria on dipstick for 3 consecutive days (or ≥3+ in some guidelines) or UPCR ≥2000 mg/g 1, 2, 3
Management of First Relapse
- Prednisone 60 mg/m²/day (maximum 60 mg) until remission for 3 consecutive days 1, 2, 3, 5
- Then switch to 40 mg/m² on alternate days for 4 weeks 1, 2, 3, 5
Common Pitfalls to Avoid
Do not treat infants <1 year with standard protocol without genetic evaluation—they likely have genetic nephrotic syndrome requiring different management 2, 3
Do not shorten initial steroid course below 12 weeks—this significantly increases relapse risk 2, 3, 8, 9
Do not routinely give albumin infusions based on laboratory values alone—reserve for clinical hypovolemia 1
Do not use aggressive diuretics without assessing volume status—can precipitate hypovolemic shock 1, 4
Do not perform routine kidney biopsy in typical presentations with steroid response 3, 4
Monitor growth velocity closely—corticosteroids suppress growth even at low doses and without HPA axis suppression 10
Do not abruptly discontinue steroids—taper gradually to minimize relapse risk and adrenal insufficiency 1, 2, 3
Steroid-Resistant Disease (If No Response by 6-8 Weeks)
If the patient fails to achieve remission after 6-8 weeks of daily prednisone:
- Diagnose steroid-resistant nephrotic syndrome (SRNS) 3
- Perform kidney biopsy to determine histopathology 1, 3
- Initiate calcineurin inhibitor therapy (tacrolimus or cyclosporine) as first-line treatment for SRNS 1, 3, 5
- Continue low-dose prednisone with CNI therapy 1
- Treat for minimum 6 months; discontinue if no partial/complete remission achieved 1