What is the best course of treatment for a 10-year-old boy with impaired renal function, significantly elevated urine protein-to-creatinine ratio, and a urine protein level of 15 mg/mg, suggestive of nephrotic syndrome?

Management of Nephrotic Syndrome in a 10-Year-Old with Severe Proteinuria

Initiate 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

Confirming the Diagnosis

A urine protein-to-creatinine ratio of 15 mg/mg (equivalent to 15,000 mg/g or 1,500 mg/mmol) represents massive nephrotic-range proteinuria, far exceeding the diagnostic threshold of ≥2,000 mg/g (≥200 mg/mmol). 2, 3, 4 This level of proteinuria, combined with impaired renal function in a 10-year-old, strongly suggests nephrotic syndrome and requires immediate treatment.

Before initiating therapy, verify the complete diagnostic triad:

• Proteinuria: Already confirmed at 15 mg/mg 2
• Hypoalbuminemia: Check serum albumin (should be ≤2.5 g/dL) 2, 4
• Edema: Document presence and severity 2, 4

Initial Corticosteroid Treatment Protocol

The standard first-line treatment follows the Kidney International consensus guidelines 1:

Daily Phase (6 weeks):

• Prednisone 60 mg/m²/day as single morning dose (maximum 60 mg/day) 1, 2
• Continue until remission is achieved, but for full 6 weeks regardless 1, 2

Alternate-Day Phase (6 weeks):

• Switch to 40 mg/m² on alternate days as single morning dose 1, 2

Tapering Phase (4 weeks):

• Reduce by 10 mg/m² per week until reaching 5 mg on alternate days 1, 2
• Total treatment duration: 16 weeks 1, 2

Expected Response and Monitoring

Remission criteria: Urine dipstick trace/negative for proteinuria for at least 3 consecutive days, or urine protein-to-creatinine ratio <200 mg/g (<20 mg/mmol). 1, 2, 5

Expected timeline: 80-94% of children achieve remission within 4-6 weeks of starting prednisone. 2 Most responders will show improvement by week 4. 2

Weekly monitoring during initial treatment 2, 5:

• Urine dipstick for protein (daily initially, then at least weekly)
• Blood pressure measurement
• Weight and edema assessment
• Serum albumin at 4-6 weeks
• Urine protein-to-creatinine ratio when dipstick becomes trace/negative

Management of Steroid Resistance

If no remission by 6-8 weeks, diagnose steroid-resistant nephrotic syndrome (SRNS) and proceed with: 1, 2, 5

1. Kidney biopsy: Essential to confirm diagnosis and guide therapy (unless genetic testing reveals familial cause). 1, 2

2. Initiate calcineurin inhibitor (CNI) therapy as first-line treatment for SRNS 1, 5:

   • Tacrolimus: 0.1 mg/kg/day (preferred) 5
   • Cyclosporine: 4-5 mg/kg/day divided into 2 doses 1
   • Target trough levels: Tacrolimus 5-8 ng/mL; Cyclosporine 47-88 ng/mL 1

3. Duration of CNI therapy 1, 5:

   • Minimum 6 months; stop if no partial/complete remission achieved 1
   • If remission achieved by 6 months, continue for at least 12 months 1, 5
   • Consider discontinuation after 12-24 months to reduce nephrotoxicity risk 1

4. Add ACE inhibitor or ARB for antiproteinuric effect and blood pressure control. 2, 5

Alternative Therapy if CNI Fails

Mycophenolate mofetil: 1,200 mg/m²/day divided into 2 doses for minimum 12 months. 1, 5 Note that cyclophosphamide is not effective for SRNS and should be avoided in this setting. 5

Supportive Care Measures

Given the impaired renal function and massive proteinuria, implement:

• Fluid management: Restrict to insensible losses plus urine output if oliguric 5
• Diuretics: Furosemide 0.5-2 mg/kg per dose (up to 6 times daily, maximum 10 mg/kg/day) for symptomatic edema 1
• ACE inhibitor/ARB: For blood pressure control and proteinuria reduction 2, 5
• Pneumococcal vaccination: If not already immunized 2
• VTE prophylaxis: Consider if albumin <2.0 g/dL 2
• Monitor for complications: Acute kidney injury, severe hypertension, pulmonary edema, infections 5

Critical Pitfalls to Avoid

• Do not perform routine kidney biopsy at initial presentation in a 10-year-old without atypical features (age <1 year, age >12 years, hematuria, hypertension, low complement, or family history). 1, 2
• Do not shorten the initial steroid course below 12 weeks, as this significantly increases relapse risk. 2
• Do not use cyclophosphamide for SRNS—it is ineffective in this setting. 5
• Monitor for steroid toxicity: Growth suppression, hypertension, hyperglycemia, behavioral changes. 1

Anticipated Relapse Pattern

Approximately 80% of children will relapse after initial treatment. 2 If relapse occurs (≥2+ proteinuria for 3 consecutive days), treat with prednisone 60 mg/m²/day until remission for 3 consecutive days, followed by 40 mg/m² alternate days for 4 weeks. 1, 2 If frequent relapses develop (≥2 relapses in 6 months), consider steroid-sparing agents such as levamisole (first-line if available) or cyclophosphamide. 1