What is the recommended initial evaluation, referral to a pediatric nephrologist, and management for a child presenting with signs suggestive of kidney disease such as persistent proteinuria, hematuria, edema, hypertension, growth failure, recurrent urinary tract infections, or abnormal renal function tests?

Childhood Kidney Disease: Initial Evaluation and Management

Immediate Referral to Pediatric Nephrology

Children presenting with combined hematuria and proteinuria require immediate pediatric nephrology referral, as this combination strongly indicates glomerular disease and carries significant risk for progressive kidney damage. 1, 2

Additional urgent referral criteria include:

• Nephrotic syndrome features: heavy proteinuria (protein-to-creatinine ratio >2 g/g), hypoalbuminemia (<2.5 g/dL), and edema 1
• Red cell casts or >80% dysmorphic RBCs on microscopy, indicating glomerular bleeding 1
• Persistent significant proteinuria (≥0.2 g/g on three separate first-morning specimens) 1, 2
• Hypertension with urinary abnormalities, suggesting acute glomerulonephritis 2
• Acute kidney injury (elevated creatinine/BUN) with hematuria or proteinuria 2
• Systemic symptoms (edema, leg pain, vomiting) combined with urinary findings 2

Initial Clinical Assessment

History—Key Elements to Elicit

• Recent streptococcal infection (pharyngitis within 1-3 weeks suggests post-infectious glomerulonephritis) 3, 2
• Family history of kidney disease, hearing loss, or early dialysis (suggests hereditary nephropathy like Alport syndrome or genetic FSGS) 3, 1
• Strenuous exercise, fever, or dehydration (may cause transient proteinuria/hematuria) 3
• Gross hematuria timing: concurrent with upper respiratory infection suggests IgA nephropathy; delayed by 1-2 weeks suggests post-infectious GN 2, 4
• Trauma history, including occult trauma or foreign body insertion 3
• Medication/supplement use and dietary factors that may discolor urine without true hematuria 3

Physical Examination—Critical Findings

• Blood pressure measurement is mandatory, as hypertension indicates glomerular disease severity 2
• Edema assessment: periorbital (especially morning) or peripheral edema suggests nephrotic syndrome or acute GN 2
• Growth parameters: height/weight plotting to detect growth failure from chronic kidney disease 3
• Rashes or arthritis (suggests vasculitis like Henoch-Schönlein purpura or lupus) 3
• Hearing assessment if Alport syndrome suspected 3
• Abdominal masses or nephromegaly 3

Essential Laboratory Workup

Urine Studies

First-morning spot urine protein-to-creatinine ratio (PCR) is the preferred method for quantifying proteinuria in children, as 24-hour collections are cumbersome and often inaccurate 1:

• Normal PCR: <0.2 g/g 1
• Significant proteinuria: ≥0.2 g/g on three separate specimens 1
• Nephrotic-range: PCR >2 g/g 1

Urinalysis with microscopy to assess for:

• Red cell casts (pathognomonic for glomerulonephritis) 1
• Dysmorphic RBCs (>80% indicates glomerular bleeding) 1
• White cells/organisms (suggests urinary tract infection requiring different evaluation pathway) 3
• Proteinuria grade: ≥1+ on dipstick warrants PCR quantification 3, 1

Spot urine calcium-to-creatinine ratio to evaluate for hypercalciuria as a cause of hematuria 3

Blood Tests

• Complete metabolic panel including albumin (hypoalbuminemia <2.5 g/dL confirms nephrotic syndrome) 2
• Serum creatinine and BUN to detect acute kidney injury 2
• Complete blood count to assess for anemia (chronic kidney disease) or thrombocytopenia 3
• Complement levels (C3, C4): low C3 suggests post-infectious GN or membranoproliferative GN 2
• Antistreptolysin O titer if post-streptococcal GN suspected 2
• Antinuclear antibody (ANA) to screen for lupus nephritis 1

Imaging Evaluation

Renal ultrasound is the first-line imaging modality to assess kidney size, echogenicity, and structural abnormalities 3, 1, 2:

• Enlarged echogenic kidneys suggest acute glomerulonephritis 2
• Small echogenic kidneys indicate chronic kidney disease 3
• Structural abnormalities (hydronephrosis, dysplasia) may explain hematuria 3
• Pre-biopsy assessment of kidney position and size 3

Ultrasound is particularly indicated for:

• Combined hematuria and proteinuria with systemic symptoms 2
• Isolated hematuria to rule out structural causes 3
• Before renal biopsy planning 3

Management Based on Diagnosis

Nephrotic Syndrome (Minimal Change Disease Most Common in Children)

Initiate corticosteroid therapy with prednisone 60 mg/m²/day once nephrotic syndrome is confirmed 1, 5:

• Renal biopsy is NOT indicated initially unless steroid-resistant after 4 weeks of treatment 1, 5
• Monitor first-morning PCR to assess treatment response 1
• Target proteinuria reduction to <0.5-1 g/day per 1.73 m² 1

Steroid-Resistant FSGS

Calcineurin inhibitor therapy (cyclosporine) is recommended for steroid-resistant cases 1:

• Start at 100 mg/m²/day in divided doses 1
• Titrate up to maximum 150 mg/m²/day 1
• Combine with alternate-day prednisone 1

IgA Nephropathy

Start ACE inhibitor or ARB for proteinuria ≥0.5 g/day per 1.73 m² 1:

• Uptitrate to achieve proteinuria <1 g/day 1

HIV-Associated Nephropathy (Relevant for At-Risk Populations)

Initiate HAART immediately as primary treatment 3:

• Add ACE inhibitor for proteinuria ≥1+ on dipstick or PCR ≥0.2 g/g on three specimens 3
• Steroids are NOT recommended for pediatric HIV nephropathy 3

Isolated Mild Proteinuria (PCR 0.2-1.0 g/g)

• Repeat first-morning PCR monthly for 3 months, then every 3-6 months 1
• Monitor blood pressure, serum creatinine, and albumin every 6 months 1
• Consider orthostatic proteinuria testing (compare first-morning to daytime specimen) 6

Genetic Testing Considerations

For children with proteinuria and family history of FSGS, initiate genetic testing in the affected family member first, followed by cascade testing 1:

• Early-onset disease (≤25 years) increases probability of genetic etiology 1
• Genetic diagnosis predicts substantially lower risk of disease recurrence after transplantation 1
• Offer genetic counseling concurrently with specialist referral 1

Monitoring Strategy

For Isolated Microscopic Hematuria Without Proteinuria

• Follow with urinalyses every 3-6 months looking for development of proteinuria 7
• Measure blood pressure and renal function tests regularly 7
• Consider renal biopsy if hematuria persists for 6-12 months with concerning features (family history of renal disease, hypertension, declining GFR) 7

For Treated Glomerulonephritis

• Monitor first-morning PCR to assess treatment response 1
• Serial albumin and creatinine measurements 1
• Target proteinuria reduction to <0.5-1 g/day per 1.73 m² 1

Common Pitfalls to Avoid

• Do not delay nephrology referral for combined hematuria and proteinuria—this combination mandates urgent evaluation 1, 2
• Do not perform renal biopsy initially for typical nephrotic syndrome in children aged 1-10 years; treat empirically with steroids first 1, 5
• Do not use 24-hour urine collections routinely in children; first-morning spot PCR is more practical and reliable 1
• Do not dismiss isolated microscopic hematuria; regular follow-up is essential as it may herald progressive disease like IgA nephropathy or Alport syndrome 7
• Do not attribute hematuria to urinary tract infection without confirming infection with culture; glomerular disease may coexist 3