Nephrotic syndrome involves an large amount of protein being lost in the urine. The basement membrane in the glomerulus becomes highly permeable to protein, allowing proteins to leak from the blood into the urine. It is most common between the ages of 2 and 5 years.
Features
Frothy urine and generalised oedema are the key presenting features.
Nephrotic syndrome involves the classic triad of:
- Proteinuria (more than 3+ on dipstick)
- Hypoalbuminaemia (low serum albumin)
- Oedema (affecting the face, legs, or generalised)
Other important features are:
- Hyperlipidaemia, with increased cholesterol and triglycerides produced by the liver
- High blood pressure due to activation of the renin-angiotensin-aldosterone system and sodium retention
- Hyper-coagulability, with an increased tendency to form blood clots
Causes
Minimal change disease causes over 90% of cases in children under 10.
It may involve intrinsic kidney disease:
- Focal segmental glomerulosclerosis
- Membranoproliferative glomerulonephritis
It can be secondary to an underlying systemic illness:
- Henoch-Schonlein purpura (HSP)
- Diabetic nephropathy (uncommon in young children)
- Infection (e.g., HIV, hepatitis or malaria)
- Malignancy (e.g., leukaemia)
Minimal Change Disease
Minimal change disease can occur in otherwise healthy children without apparent risk factors. It is not clear why it happens in most cases.
A renal biopsy and standard microscopy in minimal change disease do not detect any kidney abnormalities.
Urine microscopy shows oval fat bodies, fatty casts and hyaline casts.
TOM TIP: Minimal change disease comes up frequently in exams. In a 2-5 year old child with oedema, proteinuria and low albumin, the diagnosis is likely to be nephrotic syndrome due to minimal change disease.
Management
Nephrotic syndrome is managed by experienced paediatricians with input from renal specialists. It involves:
- High-dose steroids (prednisolone), given for 4-6 weeks, then gradually tapered
- Low salt diet
- Diuretics for severe oedema
- Albumin infusions for severe hypoalbuminaemia
- Antibiotic prophylaxis in severe cases
The response to steroids varies:
- Steroid-sensitive refers to cases that respond well to steroid treatment
- Relapse refers to recurrence of the condition, requiring further steroids (this is common)
- Steroid-dependent refers to cases involving relapse during taper or soon after stopping steroids
- Steroid-resistant refers to when proteinuria persists despite treatment with steroids
Treatment in steroid-resistance cases may involve ACE inhibitors and immunosuppressants (e.g., cyclosporine, tacrolimus or rituximab).
Complications
Hypovolaemia (low blood volume) can occur as fluid moves from the intravascular to the interstitial space. Albumin is responsible for pulling water into the blood, and in nephrotic syndrome, there is hypoalbuminaemia (low serum albumin), resulting in reduced oncotic pressure. Fluid in the interstitial space causes oedema. Reduced volume in the intravascular space leads to low blood pressure, tachycardia and poor tissue perfusion.
Thrombosis can occur because antithrombotic proteins (e.g., antithrombin III, protein C, and protein S) are lost in the kidneys and because the liver responds to low albumin by producing prothrombotic factors (e.g., fibrinogen, factor V and factor VIII).
Infection occurs as the kidneys leak immunoglobulins, weakening the immune system.
Other complications include:
- Acute kidney injury
- Chronic kidney disease
- Hyperlipidaemia
- Relapse
Last updated March 2025
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