Nephrotic syndrome

Background

• Clinical syndrome characterized by massive proteinuria, which results in hypoalbuminema, hyperlipidemia, and edema
• Can be primary (idiopathic) or secondary

Etiologies

Common

• Membranous nephropathy (24%)
• Minimal change disease (16%)
• Systemic lupus erythematosus (14%)
• FSGS (12%): more common in black patients
• Amyloidosis (6 to 17%): more common in older patients
• Membranoproliferative glomerulonephritis (7%)
• IgA nephropathy (6%)

Exhaustive

• Non-proliferative glomerulonephritis
  • Minimal change disease
    • Primary
    • Drugs
      • NSAIDs and COX-2 inhibitors
      • Ampicillin, rifampicin, cephalosporins
      • Lithium
      • D-penicillamine and tiopronin
      • Pamidronate
      • Sulfasalazine and 5-ASA
      • Interferon-gamma
    • Neosplasms
      • Hodgkin lymphoma
      • Non-Hodgkin lymphoma
      • Leukemia
    • Lupus nephritis V (membranous nephritis)
  • Focal segmental glomerulosclerosis
    • Primary
    • Severe obesity and other hyperfiltration syndromes
    • Infections: HIV, parvovirus B19, CMV, EBV
    • Drugs
      • Heroin
      • Interferons
      • Pamidronate
      • Anabolic steroids
      • mTOR inhibitors
      • Calcineurin inhibitors
      • Anthracyclines
      • Lithium
    • Other
      • Sickle cell anemia
      • Thrombotic microangiopathy
      • Genetic disorders
  • Membranous nephropathy
    • Primary
    • Systemic lupus erythematosus
    • Drugs: gold, penicillamine, NSAIDs
    • Infections: hepatitis B and hepatitis C, malaria, syphilis
    • Neoplasms
      • Non-Hodgkin lymphoma
      • Solid cancers
    • IgG4 disease

Epidemiology

• If < 20 years old
  • Minimal change (70%)
  • Membranous (20%)
  • Focal segmental glomerulosclerosis (10%)
• If > 20 years old
  • Membranous (70%)
  • Minimal change (20%)
  • Focal segmental glomerulosclerosis (10%)

Clinical Manifestations

• Edema progressing to anasarca
• May have frothy urine
• Fatigue, anorexia
• May develop DVT/PE
• Found to have proteinuria, hyperlipidemia, and hypoalbuminemia on investigations

Investigations

• For diagnosis: urine protein, lipid panel, albumin levels
• For secondary causes: send HBV, HCV, HIV, syphilis, HbA1c, ANA, SPEP/UPEP, cryoglobulins, RF, CH50, C3, C4
• Often needs kidney biopsy

Diagnosis

• Definition of the syndrome:
  • Significant proteinuria > 3g/day
  • Hyperlipidemia/lipiduria
  • Anasarca
  • Hypoalbuminemia <35g/L
• Diagnosis of the underlying cause often requires renal biopsy

Management

• If < 20 years old
  • Treat empirically with steroids, as the majority are primary minimal change disease
• If > 20 years old
  • Needs kidney biopsy to direct treatment