Nephrotic syndrome

Question 1

What is nephrotic syndrome?

Answer 1

A clinical syndrome secondary to increased permeability of serum protein through a damaged basement membrane in the renal glomerulus.

Classified as steroid-dependent or steroid-resistant

Question 2

Nephrotic syndrome is classically defined as a triad of:

Answer 2

1. Proteinuria (>1g/m2 oer 24 hours)
2. Hypoalbuminaemia (<25 g/l) ± hypercholesteraemia
3. Insidious onset oedema, starting with periorbital then generalised

Question 3

What are the other features of nephrotic syndrome?

Answer 3

=> hyperlipidaemia

=> lipiduria

=> hypercoagulable state (due to loss of antithrombin III)

=> predisposition to infection (due to loss of immunoglobulins)

=> oliguria

=> irritability

=> anorexia

=> GI disturbances / ascites

Question 4

In children the peak incidence of nephrotic syndrome is between 2 and 5 years of age.

=> 80% of cases in children are due to minimal change glomerulonephritis.
=> condition carries a good prognosis with 90% of cases responding to high-dose oral steroids.

Answer 4

Investigations:

Urine: Frothy, albuminous ± casts; low sodium

Blood: low albumin (so total calcium low); urea & creatinine normal

Renal biopsy: for older children with haematuria, raised BP, raised urea, unselective protein loss (both large and small molecular weights) and treatment failures.

Question 5

What is the pathophysiology of nephrotic syndrome?

Answer 5

Cytokines damage podocytes causing them to fuse together and destroy charge of the glomerular basement membrane.

This allows increased permeability to plasma proteins.

This causes massive protein loss in the urine.

As a result of this, serum albumin levels are reduced beyond the synthetic ability of the liver.

Thus patients experience marked oedema as with less albumin in the blood stream, there is less oncotic pressure.

This lets fluid leak out into the interstitium.

As an attempt to maintain oncotic pressure, the liver tries to compensate by increased synthesis of lipoproteins, this is one of the mechanisms postulated to cause the hyperlipidaemia.

However, the full mechanism is not fully understood.

Question 6

What are the causes of nephrotic syndrome?

Answer 6

The most common cause in children is minimal change disease (vs membranous glomerulonephritis in adults)

Question 6

What are the causes of nephrotic syndrome?

Answer 6

The most common cause in children is minimal change disease (vs membranous glomerulonephritis in adults)

Question 7

What is minimal change disease?

Answer 7

Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.

The majority of cases are idiopathic, but in around 10-20% a cause is found:

=> drugs: NSAIDs, rifampicin

=> Hodgkin’s lymphoma, thymoma

=> infectious mononucleosis

Question 8

How does minimal change disease present?

Answer 8

=> nephrotic syndrome

=> normotension - hypertension is rare

=> highly selective proteinuria => only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus

=> renal biopsy:
normal glomeruli on light microscopy

electron microscopy shows fusion of podocytes and effacement of foot processes

Question 9

How is minimal change disease managed?

Answer 9

1. majority of cases (80%) are steroid-responsive

2. cyclophosphamide for steroid-resistant cases

Question 9

How is minimal change disease managed?

Answer 9

1. majority of cases (80%) are steroid-responsive

2. cyclophosphamide for steroid-resistant cases

Question 10

How is nephrotic syndrome investigated?

Answer 10

1. Bedside investigation i.e. urine dipstick => proteinuria.
   => Urine analysis shows a raised albumin creatinine ratio.
2. Renal biopsy is indicated in all adults but should only be done in children with an atypical presentation (e.g. steroid unresponsive, haematuria, under 1 years old or over 12 years old).

Question 11

What is the treatment for nephrotic syndrome?

Answer 11

High dose steroids which should be tapered according to clinical response.

Question 12

What are the complications of nephrotic syndrome?

Answer 12

1. Infection (due to urinary loss of immunoglobulins) => pneumococcal peritonitis (consider pneumococcal vaccine if >2yrs)
2. Venous thromboembolism (due to urinary loss of antithrombin III)
3. Hyperlipidaemia (due to increased hepatic production of lipids to restore the serum oncotic pressure)

Question 13

How is nephrotic syndrome treated?

Answer 13

Get help.

1. Eat healthy - no added salts, no high protein content
2. Fluid restriction: 800-1000mL/day
3. Diuretics if very oedematous and no hypovolaemia
4. Albumin infusion only if severe hypovolaemia or severe diuretic resistant oedema
5. Prednisolone 60mg for 4 weeks then 40mg for 4 weeks then wean off
   => 90% respond in 8 weeks