• Clinical science

Nephrotic syndrome

Abstract

Nephrotic syndrome is characterized by a massive renal loss of protein (> 3.5 g/day) resulting in edema, hypercoagulability (antithrombin III deficiency), and an increased risk of infection (loss of immunoglobulins). Typical laboratory findings of nephrotic syndrome include hyperlipidemia and fatty casts on urinalysis. The most common causes of nephrotic syndrome in adults are focal segmental glomerulosclerosis and membranous nephropathy. Both diseases usually require immunosuppressive therapy. In children, nephrotic syndrome is most commonly caused by minimal change disease, a benign condition that responds well to corticosteroids. However, nephrotic syndrome can also be a manifestation of advanced renal disease (e.g., diabetic nephropathy, amyloidosis). These diseases are associated with a worse prognosis and are more difficult to treat.

Definition

Nephrotic syndrome
Proteinuria > 3.5 g/24h
Hypoalbuminemia
Edema
Hyperlipidemia


References:[1]

Etiology

Differential diagnoses of nephrotic syndrome
Associations Findings

Treatment

Minimal change disease

  • Most common cause of nephrotic syndrome in children
  • Can be associated with tumors (e.g., Hodgkin lymphoma)
  • LM: no changes
  • EM: effacement of the foot processes
Focal segmental glomerulosclerosis
  • Most common cause of nephrotic syndrome in black populations
  • Can be associated with heroin abuse, HIV infection, obesity, and sickle cell disease
  • LM: segmental sclerosis
  • IM: IgM and C3 inside the sclerotic regions
  • EM: effacement of the foot processes
Membranous nephropathy
  • Most common cause of nephrotic syndrome in white populations
  • Primary: antibodies to phospholipase A2 receptor
  • Secondary: can be associated with infections (hepatitis B and C), SLE, tumors, and medications
  • LM: glomerular capillary loops and basement membrane appear thickened
  • IM: subepithelial deposits
  • EM: subepithelial dense deposits (“spike and dome appearance”)
Membranoproliferative glomerulonephritis
  • IG-mediated
  • Complement-mediated
    • Low serum C3 levels: patients with dense deposit disease often have IgG antibodies, so-called nephritic factor, against the C3 convertase, leading to persistent complement activation.
    • IM: C3 deposits on basement membrane
  • Both:
  • No single effective treatment
Diabetic nephropathy
  • Leading cause of ESRD in the industrialized world
  • Treatment of underlying disease
Amyloidosis
  • LM: Congo red stain shows apple green birefringence under polarized light
Lupus nephritis
LM = light microscopy, IM = immunofluorescent microscopy, EM = electron microscopy

Minimal change disease is the most common cause of nephrotic syndrome in children. In adults, nephrotic syndrome is most commonly caused by focal segmental glomerulosclerosis (black populations) and membranous nephropathy (white populations)!


References:[2][3][4][5][6][7][1][8][9][10]

Pathophysiology

  • Structural damage of glomerular filtration barrier → massive renal loss of protein → reactively increased hepatic protein synthesis
    • Loss of negative charge of GBM → loss of selectivity of barrier (especially for negatively charged albumin)
    • Podocyte damage and fusion (sign of nephrotic syndrome) non-selective proteinuria
  • If protein loss exceeds hepatic synthesis (usually with a loss of protein > 3.5 g/24hours) → hypoproteinemia/hypoalbuminemia, initially both normal GFR and creatinine

References:[11][12][13]

Clinical features


References:[1]

Diagnostics


References:[1][14][15]

Pathology

Renal biopsy


References:[1][14]

Treatment

General measures

If the patient has an AT III deficiency, heparin is ineffective. Consider oral anticoagulants!

Disease-specific


References:[7][1][14][16][17][18][19]

Complications

References:[18][20][21]

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

Prognosis

  • Prognosis of minimal change disease is usually excellent
  • With a wide variety of underlying diseases, the response to treatment can differ dramatically. Even patients receiving treatment commonly develop progressive renal failure and a need for dialysis.
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last updated 10/16/2018
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