What is the management for a 6-year-old patient with nephrotic range proteinuria (protein-to-creatinine ratio of 222)?

Management of a 6-Year-Old with Nephrotic Range Proteinuria (UPCR 222 mg/mg)

This child requires immediate initiation of oral prednisone at 60 mg/m²/day (maximum 60 mg) as a single daily dose for 6 weeks, followed by 40 mg/m²/day on alternate days for another 6 weeks, then tapered over 4 weeks for a total 16-week course. 1, 2

Initial Assessment and Diagnosis

This protein-to-creatinine ratio of 222 mg/mg (equivalent to 2.22 g/g or 2220 mg/g) represents nephrotic-range proteinuria, which is defined as UPCR ≥2000 mg/g (≥200 mg/mmol) in children. 1, 3, 2

Confirm Nephrotic Syndrome Diagnosis

Before initiating treatment, verify the complete diagnostic triad:

• Proteinuria: Already confirmed with UPCR 222 mg/mg 3, 2
• Hypoalbuminemia: Check serum albumin (should be ≤2.5 g/dL for pediatric nephrotic syndrome) 1, 3, 2
• Edema: Document presence of generalized edema 3, 2

Rule Out Atypical Features Requiring Biopsy

Do NOT perform kidney biopsy initially in this 6-year-old unless atypical features are present, as minimal change disease is the most common cause (85-94% response rate to steroids). 1, 3, 4

Indications for kidney biopsy before treatment include: 1

• Age <1 year or >12 years
• Hypertension at presentation
• Azotemia/reduced kidney function
• Hypocomplementemia
• Signs of systemic illness
• Gross hematuria

Initial Corticosteroid Treatment Protocol

Standard Regimen (Total 16 weeks)

Phase 1 - Daily Prednisone (6 weeks): 1, 2

• Dose: 60 mg/m²/day (maximum 60 mg/day)
• Given as single morning dose
• Continue until remission achieved (urine dipstick trace/negative for 3 consecutive days), then continue for full 6 weeks

Phase 2 - Alternate-Day Prednisone (6 weeks): 1, 2

• Dose: 40 mg/m²/day (maximum 40 mg on alternate days)
• Given as single morning dose on alternate days

Phase 3 - Tapering (4 weeks): 1

• Taper by 10 mg/m²/week
• Continue until reaching 5 mg on alternate days
• Then discontinue

Expected Response

• Remission definition: Urine protein trace/negative (or <1+) on dipstick for 3 consecutive days, or UPCR <200 mg/g 1, 2
• Expected remission rate: 80-94% of children will achieve remission with this regimen 3, 2, 4
• Time to remission: Most children respond within 4-6 weeks 1

Monitoring During Initial Treatment

Weekly Monitoring

• Urine dipstick for protein (daily by family, reported weekly) 2
• Blood pressure 1
• Weight and edema assessment 3

Laboratory Monitoring

• Serum albumin at 4-6 weeks 3
• Confirm remission with UPCR when dipstick becomes trace/negative 1, 2

Management of Steroid Resistance

If no remission by 6-8 weeks, diagnose steroid-resistant nephrotic syndrome (SRNS): 1

Immediate Actions for SRNS

1. Perform kidney biopsy (grade A, strong recommendation) 1
2. Evaluate kidney function (GFR or eGFR) 1
3. Consider genetic testing (grade B, moderate recommendation) 1

Treatment for SRNS

First-line: Calcineurin inhibitor (CNI) therapy 1, 5

• Tacrolimus preferred over cyclophosphamide (2.64 times higher remission rate, better safety profile) 5
• Tacrolimus dose: 0.1-0.2 mg/kg/day divided into 2 doses 1
• Target trough levels: 5-8 ng/mL 1
• Continue for minimum 6 months; if partial/complete remission achieved, continue for 12-24 months 1

Alternative if CNI unavailable: Cyclophosphamide 2 mg/kg/day for 8-12 weeks (maximum cumulative dose 168 mg/kg) 1, 6

Anticipated Relapse Patterns

Approximately 80% of children will relapse after initial treatment: 2

• One-third: No relapses
• Half: Frequent relapses (≥2 in 6 months)
• Remainder: Infrequent relapses 4

Relapse Definition

• ≥2+ proteinuria on dipstick for 3 consecutive days, or
• UPCR ≥2000 mg/g (≥200 mg/mmol) 1, 2

Treatment of First Relapse

• Prednisone 60 mg/m²/day (maximum 60 mg) until remission for 3 consecutive days 1, 6, 2
• Then switch to 40 mg/m² alternate days for 4 weeks 1, 2

Common Pitfalls to Avoid

• Do not biopsy routinely at initial presentation in a 6-year-old without atypical features 1, 3
• Do not shorten the initial steroid course below 12 weeks total, as this increases relapse risk 1, 2
• Do not use cyclophosphamide as first-line for SRNS when tacrolimus is available (inferior efficacy and safety) 5
• Do not start cyclophosphamide until remission is achieved with corticosteroids 6
• Monitor for steroid toxicity (growth failure, obesity, bone disease) and consider steroid-sparing agents if frequent relapses develop 6, 4

Supportive Care

• ACE inhibitor or ARB for blood pressure control and proteinuria reduction 3
• Diuretics for symptomatic edema management 3
• Pneumococcal vaccination if not already immunized 3
• Consider VTE prophylaxis if albumin <2.0 g/dL (though less common in children than adults) 3