Nephrotic Syndrome



  • A constellation of clinical and laboratory features defined by the presence of heavy proteinuria (>3.5 g/1.73 m2/24 hr), hypoalbuminemia (<3 g/dL), severe hyperlipidemia (total cholesterol often >10 mmol/L) (380 mg/dL), and peripheral edema, with risk for thrombotic disease
  • Includes both primary (idiopathic) and secondary forms
  • Associated with many types of kidney disease


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
    • Idiopathic condition is adults associated with NSAID use or Hodgkin lymphoma.
  • Amyloidosis: 4–17%% 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%)
    • Most often primary (idiopathic) but can be secondary associated with malignancy, hepatitis B, autoimmune diseases, thyroiditis, and certain drugs including NSAIDs, penicillamine, gold, and captopril
  • Membranoproliferative glomerulonephritis (MGN)
    • May be primary or secondary
    • May present in the setting of a systemic viral or rheumatic illness

Approximately 3 cases per 100,000 per year in adults and 2 to 7 per 100,000 in Caucasian children. There is higher incidence in children of South Asian descent.


  • 16 in 100,000 children
  • More common in women than in men with a ratio of 2:1 (2)

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.
  • 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 (e.g., MCD, FSGS, MGN, IgA nephropathy)
  • Secondary renal disease (e.g., diabetic nephropathy, amyloidosis and paraproteinemias, infections, cancer, drugs)

Mutations in number of genes regulating podocyte proteins were identified in families with inherited nephrotic syndrome.

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

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