Nephrotic syndrome

by | 11 Jan, 2021

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Nephrotic syndrome is defined as the presence of:

  • Proteinuria
  • Hypoalbuminaemia
  • Peripheral oedema

It is important to note that the term nephrotic syndrome refers to a presentation of disease rather than being a disease itself. It is generally associated with the development of glomerulonephritis.

Glomerular diseases can present with features of both nephrotic and nephritic syndrome; both syndromes are considered as part of a spectrum, with some diseases being more likely to present with features of one of the syndromes.


Primary renal disease

Conditions usually presenting with nephrotic syndrome features include:

  • Minimal change disease
  • Focal segmental glomerulosclerosis (most common cause in adults)
  • Membranous glomerulonephritis
  • Thin basement membrane nephropathy

Conditions presenting with mixed nephrotic and nephritic syndrome features include:

  • IgA nephropathy
  • Membranoproliferative glomerulonephritis

Secondary renal disease

  • Diabetic nephropathy
  • Sarcoidosis
  • Autoimmune: Systemic lupus erythematosus, Sjogren’s syndrome
  • Infection: Syphilis, hepatitis B, HIV
  • Amyloidosis
  • Multiple myeloma
  • Malignancy
  • Vasculitis
  • Drugs e.g. gold, penicillamine, captopril, NSAIDs


Glomerular disease allows proteins to be filtered and excreted in urine, which also leads to hypoalbuminaemia. Consequently, peripheral oedema develops because of the loss of serum oncotic pressure as illustrated by Starling force’s law equation.

Starlings force equation
Kf: Filtration coefficient
Pc: Capillary hydrostatic pressure
Pi: Bowman’s capsule hydrostatic pressure
σ: Reflection coefficient
πc: Capillary oncotic pressure
πi: Bowman’s capsule hydrostatic pressure

Clinical features

  • Frothy urine: due to hyperlipidaemia and fatty casts in urine
  • ↑ Risk of thromboembolism: due to loss of antithrombin III in urine
  • ↑ Risk of infection: due to loss of IgG and tissue oedema, which compromises the local blood supply and immune response)
  • Generalised symptoms, including fatigue and reduced appetite


Investigations are aimed at diagnosing the underlying cause and are the same tests performed when investigating glomerulonephritis, which are as follows.

Urine tests

  • Urine dipstick
  • Urine microscopy and culture
  • Urine albumin:creatinine ratio

Blood tests

  • Urea and electrolytes
  • Full blood count
  • C-reactive protein
  • ESR
  • HbA1C
  • Immunology:
    • Complement levels
    • ANCA
    • ANA
    • Anti-dsDNA
    • Anti-GBM
    • ASOT


  • Renal ultrasound scan
  • Chest x-ray

Invasive tests

Renal biopsy


Treatment should be directed at the underlying cause of nephrotic syndrome.


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