Whatever the cause, a loss of a large amount of protein into the urine results in a presentation referred to as the nephrotic syndrome. The diagnosis can be confirmed by the presence of protein in the urine, low blood albumin and oedema.



Damage to Podocytes (glomerulus epithelial cells)  allows proteins to pass through a 'leaky' glomerulus into the urine.

  • Normally molecules of <20kDa will pass into the urine
  • In Nephrotic syndrome molecules of >100kDa can pass into the urine
  • Albumin has a molecular weight of 67kDa
Diagnostic triad

Substantial urinary protein loss (>3g/24h) produces hypoalbuminaemia and an intravascular circulation which is hypo-osmolar compared to the surrounding tissues. This resultes in movement of fluid into the surrounding tissues (oedema) and a depletion of blood volume (hypovolaemia).

This hypovolaemia stimulates the renin angiotensin aldosterone system (RAAS) to retain sodium and water. This serves to replace circulating blood volume only temporarily as the hypo-osmotic intravascular compartment loses more water into the surrounding tissues.

It is this vicious cycle which contributes most to the striking level of oedema observed in patients with nephrotic syndrome.

Clinical Picture

  • Oedema often first presents periorbitally as the tissue is low pressure in this area.
  • Ankle oedema often occurs as  a result of gravity
  • Severe proteinuria (+++) detected on  urinalysis.
  • Blood pressure is often raised in nephrotic patients and may exacerbate the condition


      More severe features occur late or if untreated and may include pulmonary effusion, genital oedema and anasarca (severe generalised oedema).


      A differential diagnosis of these symptoms includes:

      • congestive cardiac failure
      • liver failure
      • fluid overload in acute renal failure
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      Whilst 80% of nephrotic syndromes are caused by primary glomerulonephritis, (which can be diagnosed by biopsy), there is a wide variety of secondary causes which can produce protinuria.

      When to biopsy: All adults with nephrotic syndrome should be biopsied however in children the nephrotic syndrome is most often caused by minimal change glomerulornephritis and treatment with steroids should tried before resorting to biopsy.

      Complications (5 to remember)

      1. Venous thromboembolism - Results from venous obstruction by oedema, increased hepatic synthesis of clotting factors and loss of anti thrombotic factors in urine.
      2. Extreme hypercholesterolaemia (>10mmol/L) - Results from increased hepatic synthesis and decreased metabolism of lipoproteins
      3. Infection - Results from increased urinary loss of immunoglobulins and other defence proteins. Stretched skin as a result of oedema increases the liklihood of cutaneous infections.
      4. Renal Failure - Results from intravascular volume depletion (pre-renal failure). Also from Intra-renal oedema. Interstitial inflammation occurs as a result of proteinuria and may cause scarring.
      5. Malnutrition - Results from protein loss in urine

      General treatment

      3 Aims

      1) Treat fluid retention:

      • Restrict salt and water intake
      • loop diuretic +/- thiazide diuretic 
      • ACE inhibitor +/- Angiotensin 2 receptor antagonist

      2) Avoid complications:

      • prophylactic heparin
      • prompt treatment of infection
      • treat hyperlipidaemia (statins)
      • target BP 125/75

      3) Treat the underlying cause


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