Nephrotic Syndrome

Background/Epidemiology

• 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.

Pathophysiology

• 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

Investigations

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

Management

• 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

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