Nephrotic Syndrome

Question 1

Occurs when?

Answer 1

Nephrotic syndrome occurs when 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. It presents with frothy urine, generalised oedema and pallor.

Question 2

Features

Answer 2

Low serum albumin
High urine protein content (>3+ protein on urine dipstick)
Oedema
There are three other features that occur in patients with nephrotic syndrome:

Deranged lipid profile, with high levels of cholesterol, triglycerides and low density lipoproteins
High blood pressure
Hyper-coagulability, with an increased tendency to form blood clots

Question 3

Causes

Answer 3

The most common cause in children is minimal change disease, causing over 90% of cases in children under 10. In minimal change disease, nephrotic syndrome occurs in isolation, without any clear underlying condition or pathology. There are a number of secondary causes of nephrotic syndrome, where it occurs due to an underlying condition.

It can be secondary to intrinsic kidney disease:

Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
It can also be secondary to an underlying systemic illness:

Henoch schonlein purpura (HSP)
Diabetes
Infection, such as HIV, hepatitis and malaria

Question 4

Minimal Change Disease

Answer 4

Minimal change disease is the most common cause of nephrotic syndrome in children. It can occur in otherwise healthy children, without any clear risk factors or reason for developing the condition. It is not clear why it occurs in most cases.

A renal biopsy and standard microscopy in minimal change disease is usually not able to detect any abnormality. Urinalysis (analysis of the urine) will show small molecular weight proteins and hyaline casts.

Management of minimal change disease is with corticosteroids (i.e. prednisolone). The prognosis is good and most children make a full recovery, however it may reoccur.

TOM TIP: Minimal change disease comes up fairly frequently in exams as the most common cause of nephrotic syndrome in children. If you spot a 2 – 5 year old child with oedema, proteinuria and low albumin, you may be asked about the underling cause. The answer is likely to be nephrotic syndrome.

Question 5

Treatment

Answer 5

Nephrotic syndrome should be managed by experienced paediatricians with input from renal specialists. General management is with:

High dose steroids (i.e. prednisolone)
Low salt diet
Diuretics may be used to treat oedema
Albumin infusions may be required in severe hypoalbuminaemia
Antibiotic prophylaxis may be given in severe cases
High dose steroids are given for 4 weeks and then gradually weaned over the next 8 weeks:

80% of children will respond to steroids, and are referred to as steroid sensitive
80% of steroid sensitive patients will relapse at some point and need further steroids
Patients that struggle to wean steroids due to relapses are referred to as steroid dependant
Patients that do not respond to steroids are referred to as steroid resistant
In steroid resistant children, ACE inhibitors and immunosuppressants such as cyclosporine, tacrolimus or rituximab may be used.

Question 6

Complications

Answer 6

Hypovolaemia occurs as fluid leaks from the intravascular space into the interstitial space causing oedema and low blood pressure.
Thrombosis can occur because proteins that normally prevent blood clotting are lost in the kidneys, and because the liver responds to the low albumin by producing pro-thrombotic proteins.
Infection occurs as the kidneys leak immunoglobulins, weakening the capacity of the immune system to respond. This is exacerbated by treatment with medications that suppress the immune system, such as steroids.
Acute or chronic renal failure
Relapse