In a pediatric patient with edema, how can I differentiate nephrotic syndrome from nephritic syndrome using proteinuria, hypoalbuminemia, hematuria, blood pressure and renal function, and what are the first‑line treatments for each?

Differentiating Nephrotic from Nephritic Syndrome in Pediatrics

Nephrotic syndrome presents with massive proteinuria (≥40 mg/m²/hour or spot urine protein-to-creatinine ratio ≥2 g/g), hypoalbuminemia (≤2.5 g/dL), and edema, while nephritic syndrome presents with hematuria, proteinuria (typically sub-nephrotic range), hypertension, and impaired renal function. 1, 2, 3

Clinical Differentiation Algorithm

Nephrotic Syndrome Features

• Proteinuria: Massive, ≥40 mg/m²/hour or spot UPCR ≥2 g/g (≥200 mg/mmol) 4, 1, 2
• Serum albumin: ≤2.5 g/dL, often severely depressed 4, 1, 2
• Hematuria: Typically absent or microscopic only 3
• Blood pressure: Usually normal 3
• Renal function: Typically preserved initially 3
• Edema: Prominent, peripheral, gravity-dependent; may progress to anasarca and ascites 5, 6

Nephritic Syndrome Features

• Proteinuria: Present but typically sub-nephrotic range (<2 g/g) 3
• Serum albumin: May be mildly reduced but not as severely as nephrotic syndrome 3
• Hematuria: Prominent feature, often gross hematuria 3
• Blood pressure: Hypertension is characteristic 3
• Renal function: Abnormal, with elevated creatinine and reduced GFR 3
• Edema: Present but less prominent than nephrotic syndrome 3

First-Line Treatment for Nephrotic Syndrome

Initial Corticosteroid Protocol

Prednisone 60 mg/m²/day (maximum 60 mg) for 6 weeks, followed by 40 mg/m²/day on alternate days for 6 weeks, then tapered over 4 weeks for a total 16-week course. 4

• Expected remission rate: 80-94% within 4-6 weeks 4
• Weekly monitoring includes urine dipstick for protein, blood pressure, weight, and edema assessment 4
• Laboratory monitoring of serum albumin at 4-6 weeks and UPCR when dipstick becomes trace/negative 4

Supportive Management for Nephrotic Syndrome

• Diuretics: Furosemide 2-5 mg/kg/day orally in stable patients, combined with amiloride (preferred over spironolactone due to direct ENaC blockade) 7
• Fluid management: Avoid intravenous fluids and saline; concentrate oral fluid intake to prevent marked edema 7
• Albumin infusions: Only for clinical indicators of hypovolemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension), NOT based on serum albumin levels alone 7
• ACE inhibitors or ARBs: For blood pressure control and proteinuria reduction 7, 4
• Sodium restriction: Essential for edema management 5, 6

First-Line Treatment for Nephritic Syndrome

Acute Management

High-dose intravenous corticosteroids are the mainstay for crescentic nephritic syndrome with deteriorating kidney function. 7

• For crescentic disease with nephrotic syndrome and/or deteriorating kidney function, treat with intravenous corticosteroids plus cyclophosphamide 7
• Blood pressure control is critical given the characteristic hypertension 3
• Monitor renal function closely as prognosis is poorer than nephrotic syndrome 3

Specific Considerations by Etiology

• Post-infectious glomerulonephritis: Supportive care with blood pressure and fluid management; most cases self-resolve 3
• IgA nephropathy/HSP nephritis: ACE inhibitors or ARBs for persistent significant proteinuria; reserve corticosteroids for nephrotic-range proteinuria unresponsive to angiotensin blockade 7
• Lupus nephritis: Requires immunosuppression based on biopsy class 7

Critical Pitfalls to Avoid

In Nephrotic Syndrome

• Do not perform routine kidney biopsy at initial presentation in children aged 1-10 years with typical features and steroid responsiveness 4, 5
• Do not shorten the initial steroid course below 12 weeks, as this increases relapse risk 4
• Do not give albumin infusions based solely on serum albumin levels; use only for clinical hypovolemia 7
• Avoid high-dose furosemide (>6 mg/kg/day) for longer than 1 week to prevent hearing loss 7
• Stop furosemide in anuria 7

In Nephritic Syndrome

• Do not delay renal biopsy in children with decreased renal function at presentation or severe nephritic syndrome 7
• Do not use empiric immunosuppression without tissue diagnosis in suspected secondary causes 8
• Do not undertreated hypertension, as it contributes to progressive renal damage 3

When to Refer to Pediatric Nephrology

Immediate referral is required for: 8, 4

• Persistent significant proteinuria with hematuria
• Hypertension
• Elevated blood urea nitrogen/creatinine
• Age <1 year or >10 years at presentation
• Steroid resistance (no remission by 6-8 weeks) 4
• Macroscopic hematuria with proteinuria
• Low C3 complement levels