Nephrotic Syndrome


  • Classic presentation of kidney disease, although it is rare compared to reduced kidney function (eGFR), microalbuminaemia or electrolyte disturbances
  • It occurs in about 3 in 100,000 per year in adults

Clinical Features/Definition (criteria)

Proteinuria >3g/24 hours or a single urine protein:creatinine ratio of >300mg/mmol.

Serum albumin <25 or <30g/l (depending on definition).

Clinical evidence of peripheral oedema

Severe hyperlipidaemia (total cholesterol often >10mmol/l) can also be present.


  • Increased glomerular permeability to large molecules (e.g. albumin).
    • This can be congenital i.e. disorder of the genes encoding parts of the glomerular filtration barrier (consisting of a fenestrated epithelium, basement membrane and glomerular epithelium (podocytes))
    • This may also be acquired as a result of damage to the filtration barrier (commonly autoimmune but can also be vascular)
  • Loss of protein reduces the oncotic pressure within the vasculature which, in combination with high capillary hydrostatic pressures, leads to oedema
  • Other complications include increased susceptibility to infection, hyperlipidaemia, atherosclerosis, hypocalcaemia (true or false low due to low albumin and vit D), hypercoagulability (caused by a loss of coagulation proteins e.g. antithrombin III, protein C and S, with subsequent rise in fibrinogen); hypovolaemia.

Clinical Presentation

  • Ask about any other systemic symptoms, significant past medical history/past family history, drug history (including over the counter medication), any recent acute/chronic infections or diagnoses of cancer
  • Oedema is the most common feature
    • In children, this may first be seen around the face and eyes
    • In adults, this is usually first seen around the ankles
  • Patients may also feel tired, short of breath, weakness, poor appetite (weight gain is more common than loss due to oedema); abdominal pain; may have a thromboembolic event e.g. DVT, MI; may have recurrent infections
  • Other features include frothy urine


  1. Urinalysis- confirm proteinuria (2+ or greater); also check for haematuria (1+ or greater)
    1. Exclude urine infection (MSSU for microscopy, culture and sensitivity)
  2. Measure proteinuria with early morning protein:creatinine ratio (or albumin:creatinine ratio)
    • NB 24 hour urinary protein is rarely performed in practice
  3. Blood tests
    1. FBC and Coagulation, U&Es including creatinine and renal function (eGFR), LFTs, CRP and PV, glucose
    2. Calcium/bone profile
    3. Immunoglobulins, serum and urine electrophoresis
    4. Autoimmune screen if appropriate
  4. Imaging
    1. CXR (look for effusion)
    2. Abdo/renal ultrasound
  5. Biopsy
  • Remember to investigate thromboembolic risk as appropriate e.g. lipids, Doppler USS of legs, CTPA


  • Oedema
    • NB Go slow
    • Sodium/Fluid restriction (<100mmol or 3g/day and <1.5l/day)
    • Diuretics
      • Loop diuretics e.g. furosemide first line (usually high dose IV)
        • +thiazide or potassium sparing diuretics second line
        • +albumin if patient is still not responding
  • Proteinuria
    • ACE inhibitors +/- angiotensin II receptor blocker

Causes of nephrotic syndrome

  • Primary glomerular disease
    • Minimal change nephropathy
    • Focal glomerulosclerosis
    • Membranous nephropathy
    • Membranoproliferative glomerular disease
    • Mesangiocapillary glomerulonephritis
  • Secondary glomerular disease
    • Diseases
      • Diabetes mellitus
      • SLE
      • Amyloidosis
      • Cancer (in particular myeloma and lymphoma)
      • Infections
        • e.g. HIV, Hep B and C, Mycoplasma, Syphilis, Malaria, Schistosomiasis, Toxoplasmosis
    • Drugs
      • Gold, Antibiotics, NSAIDs, penicillamine, captopril, tamoxifen, lithium
    • Congenital causes
      • Alport’s syndrome
      • Congenital nephrotic syndrome (Finnish type)
      • Pierson’s, Nail-patella, Denys-Drash syndromes
    • Other
      • Pregnancy- pre-eclampsia

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: