Description

• A clinical syndrome of heavy proteinuria (>3.5 g/1.73 m²/24 hours), hypoalbuminemia, hyperlipidemia, and edema
• Includes both primary and secondary forms
• Associated with many types of kidney disease

Epidemiology

Based on definitive diagnosis:

• Diabetic nephropathy: Most common cause of secondary nephrotic syndrome (1)
• Minimal change disease (MCD):
  • Most common nephrotic syndrome in children, peaks at 2–8 years
  • Associated with drugs or lymphoma in adults
• Amyloidosis: Rare
• Lupus nephropathy (LN): Adult women are affected about 10× more often than men.
• Focal segmental glomerulosclerosis (FSGS):
  • 25% of nephrotic syndrome in adults
  • Most common primary nephrotic syndrome in African Americans
  • Has both primary and secondary forms
• Membranous nephropathy:
  • Most common primary nephrotic syndrome in Caucasians
  • Associated with malignancy and infection
• Membranoproliferative glomerulonephritis (MGN):
  • May be primary or secondary
  • May present in the setting of a systemic viral or rheumatic illness

Risk Factors

• Drug addiction (e.g., heroin [FSGS])
• Hepatitis B and C, HIV, other infections
• Immunosuppression
• Nephrotoxic drugs
• Vesicoureteral reflux (FSGS)
• Cancer (usually MGN, may be MCD)
• Chronic analgesic use/abuse
• Preeclampsia
• Diabetes mellitus

Genetics
Genetic factors are likely to play a role in susceptibility to the various nephrotic syndromes, although these have not been sufficiently defined to be useful clinically.

General Prevention

In general, there are few preventive measures, except avoidance of known causative medications.

Pathophysiology

• Increased glomerular permeability to protein molecules, especially albumin
• Edema results primarily from renal salt retention, with arterial underfilling from decreased plasma oncotic pressure playing an additional role.
• Hyperlipidemia is thought to be a consequence of increased hepatic synthesis resulting from low oncotic pressure and urinary loss of regulatory proteins.
• The hypercoagulable state that can occur in some nephrotic states is likely due to loss of antithrombin III in urine.

Etiology

• Primary renal disease:
  • MCD
  • FSGS
  • MGN
  • IgA nephropathy
  • Membranoproliferative glomerulonephritis
• Secondary renal disease (associated primary renal disease shown in parentheses):
  • Diabetic nephropathy
  • Amyloidosis
  • LN
  • FSGS
  • Infections (MGN)
  • Cancer (MCD or MGN)
  • Drugs (MCD or MGN)