Introduction
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.
Causes
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
Pathophysiology
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.

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
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
Imaging
- Renal ultrasound scan
- Chest x-ray
Invasive tests
Renal biopsy
Management
Treatment should be directed at the underlying cause of nephrotic syndrome.
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