Nephrotic syndrome

• The nephrotic syndrome describes a very classic presentation of glomerular disease that is characterised by a triad of:

  • ‘Nephrotic-range’ proteinuria (> 3.5 g/day)
  • Hypoalbuminaemia (< 35 g/L)
  • Oedema (e.g. peripheral, periorbital)
• Other features of syndrome:

  • Hyperlipidaemia - increased hepatic production of triglycerides
  • Thrombosis - loss of antithrombotic factors in the urine and increased production of prothrombotic factors in the liver
  • Immunodeficiency - loss of immunoglobulins such as IgG in the urine
  • Renal impairment and hypertension
• Primary causes:

  • Minimal change disease (most common cause in children)
  • Membranous glomerulo-nephropathy (most common cause in adult)
  • Focal segmental glomerulosclerosis
• Secondary causes:

  • Diabetes mellitus
  • Amyloidosis - extracellular protein deposits
  • HIV
• Nephrotic syndrome is typically caused by disease which damage the filtration barrier and the glomerular basement membrane
• Due to loss of protein (principally albumin) across the glomeruli there is loss of oncotic pressure and increased movement of fluid into the interstitial space that leads to oedema.
• Symptoms:

  • Fatigue
  • Poor appetite
  • Peripheral oedema
  • Periorbital oedema
  • SOB - pleural effusions and/or pulmonary oedema
  • Foamy urine - due to excess protein loss
• Signs:

  • Oedema - peripheral, periorbital
  • Ascites
  • Effusions - dull percussion note and reduced air entry
• Diagnosis:

  • Identification of the typical triad
  • Lipid profile
  • Coagulation
  • Renal function
  • Renal biopsy often required for diagnosis
• General management:

  • Monitor renal function
  • Lowering BP
  • ACEi/ARB to reduce proteinuria
  • Treating oedema (usually with furosemide, salt and fluid restriction)
  • Treat high cholesterol - statin
  • Managing thrombotic risk/complications
  • Pneumococcal vaccine due to immunosuppression
• Immunosuppression regimen depends on underlying cause:

  • Minimal change disease and FSGS - usually treated with prednisolone
  • Membranous nephropathy - may include steroids and cyclophosphamide, or rituximab
• Taking NSAIDs is a risk factor for nephrotic syndrome
• Thrombotic complications:

  • Can occur in both the arterial and venous system
  • DVT and PE are particularly common
  • Patients should be assessed for leg swelling and features of PE
  • Loss of anticoagulants through urine
  • Increased levels of fibrin and platelet activation in the liver
• Hyperlipidaemia:

  • Hypercholesterolaemia
  • Hypertriglyceridaemia
  • Increased rate of lipoprotein synthesis in the liver
  • Impaired metabolism of triglycerides
  • Managed with statins
• The principal treatment of minimal change disease is systemic glucocorticoids (e.g. prednisolone). This will usually lead to complete remission.
• Focal segmental glomerulosclerosis describes a histological lesion seen in some cases of nephrotic syndrome.

  • Sclerosis in parts of at least one glomerulus
  • Primary FSGS is treated with steroids
  • Secondary FSGS represents an adaptive response to renal injury