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Nephrotic Syndrome

Nephrotic syndrome is a kidney condition characterised by a collection of symptoms due to damage to the glomeruli. It includes significant protein in the urine (proteinuria), low blood albumin levels (hypoalbuminaemia), high blood lipids (hyperlipidaemia), and notable swelling (oedema).

Other symptoms may include weight gain, feeling tired, and foamy urine. It primarily falls under the specialty of nephrology.

Microscopic image of diabetic glomerulosclerosis, the main cause of nephrotic syndrome in adults.
Microscopic image of diabetic glomerulosclerosis, the main cause of nephrotic syndrome in adults.

Signs and Symptoms

Nephrotic syndrome presents with varying degrees of fluid retention, ranging from mild eyelid oedema to generalised swelling (anasarca). The most common signs are proteinuria (>3.5 g per 1.73 m² per day), hypoalbuminaemia (<3.5 g/dL), and hyperlipidaemia. Lipiduria can also occur but is not essential for diagnosis.

Nephrotic syndrome with facial oedema.
Nephrotic syndrome with facial oedema.

Other clinical characteristics include:

  • Puffy eyes, especially in the morning
  • Pitting oedema in the legs
  • Pleural effusion and pulmonary oedema
  • Ascites and generalised anasarca
  • Possible hypertension (though most are normotensive)
  • Iron-resistant microcytic hypochromic anaemia
  • Dyspnea from pleural effusion or diaphragmatic compression due to ascites
  • Increased erythrocyte sedimentation rate
  • Foamy or frothy urine due to severe proteinuria
  • Symptoms of the underlying cause, like rashes in systemic lupus erythematosus or neuropathy in diabetes
  • Muehrcke's nails (white lines across nails)

Complications

Complications of nephrotic syndrome include blood clots, infections due to loss of immunoglobulins, acute kidney failure due to hypovolaemia, pulmonary oedema, hypothyroidism, vitamin D deficiency, hypocalcaemia, iron deficiency, protein malnutrition, growth retardation, and Cushing's syndrome.

Causes

Nephrotic syndrome can arise from primary glomerular diseases such as minimal change disease (most common in children), focal segmental glomerulosclerosis (most common in adults), membranous glomerulonephritis, membranoproliferative glomerulonephritis, and rapidly progressive glomerulonephritis. Secondary causes include diabetes, systemic lupus erythematosus, sarcoidosis, syphilis, hepatitis B, Sjögren's syndrome, HIV, amyloidosis, multiple myeloma, vasculitis, cancer, genetic disorders, and certain drugs.

Histological image of a normal kidney glomerulus.
Histological image of a normal kidney glomerulus.
Diabetic glomerulonephritis in a person with nephrotic syndrome.
Diabetic glomerulonephritis in a person with nephrotic syndrome.

Pathophysiology

The kidney glomerulus filters blood, allowing small molecules but not proteins to pass through. In nephrotic syndrome, glomerular damage allows proteins like albumin to appear in urine. Hypoproteinaemia leads to decreased oncotic pressure, causing fluid leakage into tissues and leading to oedema. The liver compensates by producing proteins, including lipoproteins, causing hyperlipidaemia.

Drawing of the kidney glomerulus.
Drawing of the kidney glomerulus.

Diagnosis

Diagnosis involves urinalysis to detect proteinuria, blood tests for hypoalbuminaemia, and creatinine clearance to assess kidney function. Lipid profiles may show hypercholesterolaemia. Kidney biopsy can identify glomerulonephritis type but is typically reserved for adults or corticosteroid-resistant children.

Urinalysis will be able to detect high levels of proteins and occasionally microscopic haematuria.
Urinalysis will be able to detect high levels of proteins and occasionally microscopic haematuria.
Ultrasound of a kidney with nephrotic syndrome.
Ultrasound of a kidney with nephrotic syndrome.

Treatment

Treatment aims to address the underlying cause and manage symptoms and complications. Symptomatic treatment includes rest, a low-salt diet, diuretics for oedema, moderate protein intake, and medications for hyperlipidaemia and thrombophilia. Infectious complications require antibiotics.

Symptomatic Treatment

  • Oedema: Rest, low-sodium diet, diuretics.
  • Hypoalbuminaemia: Moderate intake of animal proteins.
  • Hyperlipidaemia: Low-cholesterol diet, possibly hypolipidaemic drugs.
  • Thrombophilia: Low molecular weight heparin and oral anticoagulants as needed.
  • Infectious Complications: Appropriate antibacterial drugs.

Kidney Damage Treatment

Medications include corticosteroids, which are effective in reducing proteinuria and oedema, and immunosuppressants like cyclophosphamide for corticosteroid-dependent or intolerant individuals.

Prognosis

The prognosis depends on the cause, age, and response to treatment. Children generally have a good prognosis, particularly with minimal change disease. Adults and those with focal segmental glomerulosclerosis or rapidly progressing glomerulonephritis have a poorer prognosis, often progressing to chronic kidney failure.

Epidemiology

Nephrotic syndrome affects both adults and children, with different underlying causes. It is more common in adults and presents differently across age groups. Men are affected more frequently than women. Spontaneous remission is possible but not definitive, and long-term prognosis varies with potential for chronic kidney failure and cardiovascular complications.


Self-assessment MCQs (single best answer)

Which of the following is NOT a typical symptom of nephrotic syndrome?



What is the most common cause of nephrotic syndrome in children?



Which of the following laboratory findings is essential for the diagnosis of nephrotic syndrome?



What is the role of the liver in the pathophysiology of nephrotic syndrome?



Which complication is NOT commonly associated with nephrotic syndrome?



What is the first-line treatment for reducing proteinuria and oedema in nephrotic syndrome?



Which of the following is a secondary cause of nephrotic syndrome?



In nephrotic syndrome, why does hypoalbuminaemia lead to oedema?



Which diagnostic test is used to assess kidney function in nephrotic syndrome?



What is the main histological feature seen in diabetic glomerulosclerosis?



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