What is the evaluation and management approach for a pediatric patient with proteinuria (presence of protein in the urine) detected on urinalysis (UA)?

Evaluation and Management of Proteinuria in Pediatric Patients

Pediatric patients with proteinuria detected on urinalysis should undergo quantitative measurement with urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) on a first morning void sample, followed by appropriate evaluation based on severity, persistence, and associated clinical findings. 1

Initial Assessment

Quantification of Proteinuria

• First morning void sample is preferred to rule out orthostatic proteinuria
• Laboratory quantification methods:
  • Urine protein-to-creatinine ratio (PCR)
  • Urine albumin-to-creatinine ratio (ACR)
  • Both should be tested in children for comprehensive assessment 1

Classification of Proteinuria

1. Transient (functional) proteinuria

   • Temporary and resolves when triggering factor is removed
   • Common causes: fever, exercise, stress, cold exposure 2

2. Orthostatic proteinuria

   • Most common type in children, especially adolescent males
   • Benign condition without clinical significance
   • Protein present in urine collected in upright position, absent in first morning void 2

3. Persistent proteinuria

   • May indicate underlying renal disease
   • Can be glomerular or tubulointerstitial in origin 2

Diagnostic Algorithm

Step 1: Confirm and Quantify Proteinuria

• If dipstick positive, confirm with laboratory PCR/ACR measurement 1
• PCR >0.2 g/g (or >200 mg/g) is considered abnormal in children 3

Step 2: Determine if Orthostatic vs. Persistent

• Collect first morning void (before getting out of bed)
• If first morning sample is negative but random samples positive → orthostatic proteinuria
• If first morning sample is positive → persistent proteinuria

Step 3: Assess for Red Flags Requiring Prompt Referral

Immediate referral to pediatric nephrologist if any of the following are present 1:

• Nephrotic-range proteinuria (PCR >2000 mg/g)
• Proteinuria with hematuria
• Proteinuria with hypertension
• Proteinuria with reduced GFR
• Proteinuria with edema or hypoalbuminemia

Management Based on Proteinuria Type

Transient/Orthostatic Proteinuria

• Generally benign conditions requiring monitoring but not specific treatment
• Follow-up urinalysis in 3-6 months to confirm resolution or stability
• Annual monitoring if stable orthostatic proteinuria 2

Mild Persistent Proteinuria (PCR <1 g/g)

• Monitor every 3-6 months with urinalysis, blood pressure, and renal function
• Evaluate for underlying causes
• Consider referral to pediatric nephrology if persistent beyond 6 months

Moderate to Severe Proteinuria (PCR >1 g/g)

• Refer to pediatric nephrologist
• For proteinuric nephropathies, ACE inhibitors or ARBs should be considered as first-line therapy 3, 1
• Start with low dose and titrate upward as tolerated
• Monitor serum creatinine and potassium 1-2 weeks after starting treatment 1

Nephrotic Syndrome

• Defined as massive proteinuria (>40 mg/m²/hr), hypoalbuminemia (<25 g/L), and generalized edema 4
• Immediate referral to pediatric nephrology
• Prednisone may be indicated for idiopathic nephrotic syndrome 5

Special Considerations

HIV-Associated Nephropathy

• In HIV-infected children, screening should include complete urinalysis and testing for serum electrolytes, BUN, and creatinine every 6 months 3
• HIV-associated proteinuric nephropathies should be treated with antiretroviral therapy
• Consider ACE inhibition for more severe proteinuria (grade 1+ by dipstick or PCR >0.2 g/g for 3 separate specimens) 3

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• Prevalence of proteinuria in children with ADPKD is approximately 20%
• Proteinuria is a risk factor for CKD progression
• ACE inhibitors or ARBs are recommended as primary treatment for children with ADPKD who have proteinuria 3

Common Pitfalls to Avoid

• Relying on dipstick testing alone - Confirm with quantitative PCR/ACR
• Using 24-hour collections unnecessarily - Spot PCR/ACR is reliable and more practical in children
• Ignoring factors affecting interpretation such as:
  • Exercise before sample collection
  • Fever or infection
  • Concentrated urine
  • Hematuria (falsely elevates PCR/ACR)
• Failing to distinguish orthostatic from pathological proteinuria
• Not considering combined hematuria and proteinuria - This combination significantly increases the likelihood of significant renal disease 6

Follow-up Recommendations

• Orthostatic/transient proteinuria: Annual monitoring
• Mild persistent proteinuria: Every 3-6 months
• Moderate-severe proteinuria or with risk factors: Refer to nephrology for management and follow-up plan

Remember that while most cases of isolated proteinuria in children are benign, persistent proteinuria may be an independent risk factor for progression of chronic kidney disease and requires appropriate evaluation and management.