Which features differentiate nephritic from nephrotic syndrome?

Differentiating Nephritic from Nephrotic Syndrome

The degree of proteinuria (Option E) is the single most reliable feature that differentiates nephritic from nephrotic syndrome, with nephrotic syndrome defined by proteinuria ≥3.5 g/day (or protein-creatinine ratio ≥3.5 g/g) versus the lower-grade proteinuria typically seen in nephritic syndrome. 1, 2, 3

Why Degree of Proteinuria is the Key Differentiator

Nephrotic syndrome requires heavy proteinuria (≥3.5 g/24 hours in adults; ≥1.0 g/m²/day in children), while nephritic syndrome presents with proteinuria but typically below nephrotic range. 4, 2, 3 The KDIGO guidelines specifically define nephrotic-range proteinuria as protein excretion rate >3500 mg/day or protein-creatinine ratio >3500 mg/g (>350 mg/mmol). 1

For practical purposes, a urine protein-creatinine ratio >300-350 mg/mmol indicates nephrotic-range proteinuria and strongly suggests nephrotic syndrome rather than nephritic syndrome. 2

Why Other Options Are Less Discriminatory

Presence of Edema (Option A)

• Both syndromes can present with edema, making this feature non-discriminatory. 2, 3
• Nephrotic syndrome causes edema through decreased oncotic pressure from albumin loss 4
• Nephritic syndrome causes edema through salt and water retention from decreased GFR 3

Presence of Hypertension (Option B)

• Hypertension occurs in both conditions, though it is more characteristic of nephritic syndrome. 3
• Nephritic syndrome is typically associated with hypertension as a prominent feature 3
• However, hypertension can also occur in nephrotic syndrome, particularly in membranous nephropathy and FSGS 4, 5

Presence of Hematuria (Option C)

• While hematuria is more characteristic of nephritic syndrome, its presence alone does not definitively exclude nephrotic syndrome. 3
• Nephritic syndrome is associated with hematuria (often with dysmorphic RBCs and RBC casts) 3
• Some nephrotic conditions like FSGS can present with hematuria 4, 5
• The absence of macroscopic hematuria is more suggestive of minimal change disease within nephrotic syndrome 6

Presence of Proteinuria (Option D)

• Both syndromes have proteinuria, so mere presence is not discriminatory—only the degree matters. 3

Clinical Algorithm for Differentiation

When evaluating a patient with suspected glomerular disease:

1. Quantify proteinuria first using 24-hour urine collection or spot protein-creatinine ratio 2

   • If ≥3.5 g/day (or PCR ≥3500 mg/g): Consider nephrotic syndrome 1, 2
   • If <3.5 g/day: More consistent with nephritic syndrome 3

2. Assess for additional nephrotic features (if proteinuria is nephrotic-range):

   • Hypoalbuminemia (<3.0 g/dL in adults; <2.5 g/dL in children) 4, 2
   • Hyperlipidemia 2, 3
   • Edema (often periorbital in morning, dependent later) 2

3. Assess for nephritic features (if proteinuria is sub-nephrotic):

   • Active urinary sediment with dysmorphic RBCs or cellular casts 4
   • Hypertension as a prominent feature 3
   • Abnormal kidney function/rising creatinine 3

Critical Pitfall to Avoid

Do not assume that the presence of hematuria automatically excludes nephrotic syndrome. Some primary nephrotic conditions (particularly FSGS and membranous nephropathy with concurrent IgA nephropathy) can present with both nephrotic-range proteinuria and hematuria. 4, 5 The degree of proteinuria remains the most reliable discriminator, and patients with nephrotic-range proteinuria should be evaluated for nephrotic syndrome regardless of hematuria presence. 1, 2