Description

• A clinical syndrome of massive proteinuria (>3.5 g/1.73 m²/24 hr), hypoalbuminemia (<3 g/dL), severe hyperlipidemia (total cholesterol often >10 mmol/L) (380 mg/dL), clinical evidence of peripheral edema, with risk for thrombotic disease
• Includes both primary (idiopathic) 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 cause of nephrotic syndrome in children <10 years (90%)
  • Peaks at 2 to 8 years of age
  • Associated with drugs (mainly NSAIDs) or lymphoma in adults
• Amyloidosis: 7–14% of idiopathic nephrotic syndrome—two renal types primary (AL) and secondary (AA)
• Lupus nephropathy (LN): Adult women are affected about 10 times more often than men.
• Focal segmental glomerulosclerosis (FSGS)
  • 35% of nephrotic syndrome in adults
  • Most common primary nephrotic syndrome in African Americans
  • Has both primary (idiopathic) and secondary forms (associated with HIV, morbid obesity, reflux nephropathy, previous glomerular injury)
• Membranous nephropathy
  • Most common cause of primary nephrotic syndrome in adults (40%)
  • May be primary or secondary associated with malignancy, Hep B, autoimmune diseases, thyroiditis, and certain drugs
• Membranoproliferative glomerulonephritis (MGN)
  • May be primary or secondary
  • May present in the setting of a systemic viral or rheumatic illness

Etiology and Pathophysiology

• Increased glomerular permeability to protein macromolecules, especially albumin
• Podocytes injury is the most common finding in diseases that cause primary nephrotic syndrome.
• Mutations in number of genes regulating podocyte proteins were identified in families with inherited nephrotic syndrome.
• 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.
• Primary renal disease:
  • MCD
  • FSGS
  • MGN
  • IgA nephropathy
• 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)

Genetics
Genetic factors are likely to play a role in the susceptibility and clinical unresponsiveness to glucose steroids, but the exact mechanism remains largely unknown.

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 (NSAIDs)
• Preeclampsia
• Diabetes mellitus

General Prevention

In general, there are few preventive measures, including avoidance of known causative medications including NSAIDs, gold, penicillamine, and captopril; avoidance of heroin abuse and tight glycemic control