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