Description

• 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

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
  • 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

Incidence
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.

Prevalence

• 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)

Genetics
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