What is the difference between nephritic and nephrotic syndrome?

Differences Between Nephritic and Nephrotic Syndrome

Nephrotic syndrome and nephritic syndrome are distinct glomerular disorders with different clinical presentations, pathophysiology, and management approaches.

Key Differences

Definition and Clinical Features

Nephrotic Syndrome:

• Primary features:
  • Heavy proteinuria (≥3.5 g/day in adults; ≥40 mg/m²/h in children) 1
  • Hypoalbuminemia (<3.0 g/dL) 1
  • Edema 1
  • Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) 2
  • Lipiduria 2

Nephritic Syndrome:

• Primary features:
  • Hematuria (primary feature) 3, 4
  • Proteinuria (typically non-nephrotic range) 3
  • Hypertension 3
  • Acute kidney injury (variable) 3
  • Fluid retention 3

Pathophysiology

Nephrotic Syndrome:

• Results from damage to podocytes and glomerular basement membrane 1
• Increased permeability of glomerular filtration barrier to proteins 1
• T-cell dysfunction may be responsible in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) 1
• Evidence suggests a "glomerular permeability factor" that interferes with albumin filtration 1

Nephritic Syndrome:

• Results from inflammatory injury to glomeruli 3
• Often involves immune complex deposition and complement activation 4
• Associated with inflammatory cell infiltration 3

Common Causes

Nephrotic Syndrome:

• Children: Minimal change disease (most common) 5
• Adults:
  • White adults: Membranous nephropathy (most common) 5
  • African ancestry: Focal segmental glomerulosclerosis (most common) 5
  • Diabetic nephropathy (most common secondary cause) 5

Nephritic Syndrome:

• Post-infectious glomerulonephritis 4
• IgA nephropathy 4
• Lupus nephritis 4
• Membranoproliferative glomerulonephritis 3
• ANCA-associated vasculitis 3

Complications

Nephrotic Syndrome:

• Thromboembolism (high risk, especially with serum albumin <2.9 g/dL) 1
• Infections (particularly cellulitis and spontaneous bacterial peritonitis in children) 1
• Accelerated coronary heart disease (4× higher risk) 1
• Progressive kidney failure 1

Nephritic Syndrome:

• Hypertension (more severe) 3
• Acute kidney injury (more common) 3
• Generally poorer prognosis compared to nephrotic syndrome 4

Diagnostic Approach

Nephrotic Syndrome:

• Quantify proteinuria: Urine protein:creatinine ratio (PCR) >300-350 mg/mmol indicates nephrotic range 5
• Serum albumin measurement 1
• Lipid profile 1
• Renal biopsy (to determine specific histological variant) 5

Nephritic Syndrome:

• Urinalysis (for hematuria, RBC casts) 3
• Assessment of kidney function (creatinine, eGFR) 3
• Blood pressure measurement 3
• Complement levels (often low in post-infectious GN, lupus nephritis) 4
• Renal biopsy 3

Treatment Approach

Nephrotic Syndrome:

• Depends on histological subtype:
  • MCD/FSGS: Corticosteroids as first-line (prednisone 1 mg/kg/day) 1
  • Steroid-resistant cases: Calcineurin inhibitors (cyclosporine) 1
  • Supportive care: ACE inhibitors, diuretics, statins 1
  • Anticoagulation if serum albumin <2.9 g/dL 1

Nephritic Syndrome:

• Treatment of underlying cause (e.g., antibiotics for post-infectious GN) 4
• Blood pressure control 4
• Immunosuppression for specific causes (e.g., cyclophosphamide or mycophenolate mofetil for lupus nephritis) 1

Clinical Pearls and Pitfalls

1. Overlapping features: Some glomerular diseases can present with features of both syndromes (e.g., membranoproliferative GN) 4

2. Prognostic implications: Nephritic syndrome generally carries a poorer prognosis than pure nephrotic syndrome 4

3. Thrombotic risk: Nephrotic syndrome has a particularly high risk of venous thromboembolism, especially with membranous nephropathy 1

4. Monitoring: Duration and severity of proteinuria are key surrogate markers for progression in both syndromes 1

5. Referral: Urgent referral to nephrology (within 2 weeks) is recommended for both syndromes for proper diagnosis and management 5