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Nephrotic syndrome


Nephrotic syndrome is a collection of signs and symptoms indicating damage to the glomerular filtration barrier. It is characterized by massive proteinuria (> 3.5 g/24 hours), hypoalbuminemia, and edema. In adults, the most common causes of nephrotic syndrome include focal segmental glomerulosclerosis (FSGS) and membranous nephropathy. In children, nephrotic syndrome is most commonly caused by minimal change disease (MCD). Nephrotic syndrome can also be a manifestation of advanced renal disease in systemic conditions (e.g., diabetic nephropathy or amyloid nephropathy). Typical laboratory findings of nephrotic syndrome include hyperlipidemia and fatty casts on urinalysis. Treatment for FSGS, membranous nephropathy, and MCD usually includes immunosuppressive therapy. Nephrotic syndrome due to advanced renal disease is associated with a worse prognosis and is more difficult to treat.

See the section “Core IM podcast 5 pearls on nephrotic syndrome” for their complete show notes on this topic.



Differential diagnoses of nephrotic syndrome [2][3][4][5][6]
Disease Epidemiology




Minimal change disease (lipid nephrosis)

  • Most common cause of nephrotic syndrome in children
Focal segmental glomerulosclerosis
  • Most common cause of nephrotic syndrome in adults, especially in African American and Hispanic populations
  • LM: segmental sclerosis and hyalinosis
  • IM
    • Most commonly negative
    • Possibly IgM, C1, and C3 deposits inside the sclerotic regions
  • EM: effacement of podocyte foot processes (similar to minimal change disease)
Membranous nephropathy
  • Most common cause of nephrotic syndrome in adults of European, Middle Eastern, or North African descent
Diabetic nephropathy
  • Leading cause of ESRD in high-income countries
  • Usually additional signs of other organ system complications (e.g., retinopathy, neuropathy)
  • LM
    • Thickening of the glomerular basement membrane (increased permeability)
    • Eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)
    • Mesangial matrix expansion
Amyloid nephropathy
  • More commonly seen in elderly patients [11]
Membranoproliferative glomerulonephritis
LM = light microscopy, IM = immunofluorescent microscopy, EM = electron microscopy


Nephrotic syndrome may be caused by primary glomerular disorders (80–90% of cases) and/or systemic diseases and toxic exposures (10–20% of cases). [12]


Damage of glomerular filtration barrier [13][14]

FSGS is classically not associated with immune complex deposition.

Sequelae of glomerular filter damage [13][14]

Clinical features



  1. Confirm nephrotic-range proteinuria.
  2. Assess for potential concomitant and underlying conditions.
  3. Assess for nephrotic syndrome complications.
  4. Consider kidney biopsy to determine renal pathology.

Initial evaluation [22][12]

Confirmation of nephrotic-range proteinuria

  • Qualitative assessment by urine dipstick (commonly used for screening)
    • Usually shows ≥ 3+ proteins
    • Hematuria may indicate concomitant glomerulonephritis.
  • Quantitative assessment of urine protein excretion
    • 24-hour urine protein (test of choice): > 3.5 g/24 hours [23][24][25]
    • Spot urine protein/creatinine ratio: > 3.5 g/g [26][23]

Urine sediment microscopy [27]

Additional laboratory studies


Subsequent evaluation [22][12]

Additional testing to assess for potential concomitant conditions and underlying causes should be based on clinical suspicion. [30]

Work-up for concomitant conditions and underlying causes of nephrotic syndrome
Suspected condition Recommended studies
Diabetic nephropathy
Membranous nephropathy
Lupus nephritis

Multiple myeloma

and other plasma cell dyscrasias

Chronic viral infection
Congenital nephrotic syndromes
  • Genetic testing

Renal biopsy [22][12]

  • Indication: to confirm the diagnosis when the etiology of nephrotic syndrome is unclear and/or to guide management
    • Often required in adult patients to guide management.
    • Sometimes deferred when a likely cause of nephrotic symptoms is evident [31][32]
    • Consult nephrology to determine the necessity and timing of biopsy.
  • Interpretation: See the “Pathology” section.


Classification of nephrotic syndrome is based on the pattern of injury as seen on light microscopy (LM) of a renal biopsy specimen. For a complete assessment, all biopsy specimens should be analyzed using LM, immunofluorescence microscopy (IM), and electron microscopy (EM).


Management of symptoms and complications of nephrotic syndrome [22][12][1]

Edema [22][12][1]

Proteinuria [22][12][1]

Elimination or reduction of proteinuria; is a major treatment goal for nephrotic syndrome and can lead to increased serum albumin, decreased edema; , attenuation of the metabolic effects of heavy proteinuria; (e.g., hyperlipidemia), reduction in risk of thromboembolism and infection, and slowing of the progression of chronic kidney disease.

Dyslipidemia [22][1][39]

  • Lipid-lowering therapy (e.g., atorvastatin )
  • Indications similar to those in other patients with a high risk of cardiovascular disease (See “Treatment” in “Lipid disorders”)

Hypercoagulability [1][22][40]

All patients with nephrotic syndrome are at increased risk of thromboembolism, and this risk becomes progressively higher as serum albumin drops below 3.0 g/L.

Infectious risk [41]

Disease-specific measures [1][32]

Primary membranous nephropathy [1]

Primary (idiopathic) focal segmental glomerulosclerosis (FSGS) [1]

Primary (idiopathic) minimal change disease (MCD) [1]

Diabetic nephropathy [43]

Amyloid nephropathy [44]

Lupus nephritis


We list the most important complications. The selection is not exhaustive.

Differential diagnoses

The differential diagnoses listed here are not exhaustive.


  • The prognosis for minimal change disease is usually excellent.
  • With a wide variety of underlying diseases, the response to treatment can differ dramatically. Individuals with nephrotic syndrome often develop progressive renal failure despite treatment and go on to require dialysis.

Core IM podcast: 5 pearls on nephrotic syndrome

Amboss has partnered with the popular Core IM podcast to bring you digestible internal medicine content on complex medical topics. In this section, you’ll find their 5 clinical pearls on the diagnosis and management of nephrotic syndrome. Check out their website for the full show notes and listen to our coproduced episode on your favorite podcast platform.