Nephrotic Syndrome

Basics

Description

Diseases causing defect in glomerular filtration barrier, producing proteinuria:
- Proteinuria >3 g in 24 hr
- Hypoalbuminemia (serum albumin <3 g/dL)
- Peripheral edema due to hypoalbuminemia
- Hypogammaglobulinemia
- Hyperlipidemia (fasting cholesterol >200 mg/dL)
Urine fat (oval fat bodies, fatty/waxy casts)
Glomerular basement membrane altered by:
- Immune complexes
- Nephrotoxic antibodies
- Nonimmune mechanisms
- Result: More permeable glomerular membranes and excretion of albumin and large proteins

Pathophysiology

Proteinuria due to increased filtration within renal glomeruli
Edema due to sodium retention and hypoalbuminemia
Postural hypotension, syncope, and shock due to severe hypoalbuminemia
Hyperlipidemia due to hepatic lipoprotein synthesis stimulated by decreased plasma oncotic pressure
Cumulative thromboembolism risk increased if:
- Hypovolemia
- Low serum albumin
- High protein excretion
- High fibrinogen levels
- Low antithrombin III levels

Etiology

Due to primary renal or systemic diseases
Membranous nephropathy:
- Primary cause of nephrotic syndrome in adults
- Other causes include chronic infection (hepatitis B virus, hepatitis C virus, autoimmune disorders)
- Renal biopsy shows involvement of all glomeruli
- Women have better prognosis
- 30% may slowly progress to renal failure
- Renal vein thrombosis causes sudden loss of renal function
- Treat with steroids and cytotoxic agents in severe cases
Minimal change disease:
- Most common cause (90%) of nephrotic syndrome in children
- Other causes: Idiopathic, NSAIDs, paraneoplastic syndrome associated with malignancy (often Hodgkin lymphoma)
- Best prognosis among all nephrotic syndromes
- Good response to steroids
Focal segmental glomerulosclerosis (FSGS):
- Young patients (15–30 yr) with nephrotic syndrome
- Presents with high BP, renal insufficiency, proteinuria, microscopic or gross hematuria
- Causes include HIV, heroin abuse, obesity, hematologic malignancies
- Primary FSGS responds to steroids
- Secondary FSGS treated with ACE inhibitors (ACEI)
- Collapsing FSGS usually seen in HIV patients
Membranoproliferative glomerulonephritis:
- May present with nephrotic, nonnephrotic, or nephritic sediment
- Complement levels are persistently low
- Supportive care: Steroids may be helpful in children
- Aspirin and dipyridamole may slow progression
Diabetes mellitus/diabetic nephropathy:
- Most common secondary cause of nephrotic range proteinuria in adults
- Microalbuminuria (30–300 mg/24 hr) is primary indicator of renal disease
- Worsening of renal function in 5–7 yr
- Does not cause rapid decline in renal function
- Strict control of blood sugar and ACEI therapy slow progression
Monoclonal gammopathies:
- Include amyloidosis, multiple myeloma, and light-chain nephropathy
- Renal manifestations include proteinuria, nephrotic syndrome, nephritic syndrome, and acute renal failure
- Lab findings include pseudohyponatremia, low anion gap, hypercalcemia, and Bence Jones proteinuria
- Congo red stain of amyloid shows apple-green birefringence in polarized light
- Supportive care: Steroids and melphalan have some benefit
Systemic lupus erythematosus (SLE):
- Can present initially as a nephritic process, with progression to nephrotic syndrome
HIV-associated nephropathy:
- FSGS is most common nephropathy
- Collapsing glomerulopathy in seropositive HIV carriers with supernephrotic syndrome results in end-stage renal failure that is rapidly progressive (months)
Other causes include preeclampsia, hepatitis, and drug reactions (culprits include NSAIDs, gold, penicillamine)

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