Renal disease in a child: Nephrotic syndrome

Question 1

Define nephrotic syndrome.

Answer 1

Characerised by hypoalbuminaemia, proteinureia and oedema.

Question 2

Explain the aetiology of nephrotic syndrome.

Answer 2

All causes of glomerulonephritis (GN) can cause nephrotic syndrome.

Question 3

What is primary nephrotic syndrome?

Answer 3

Described by histology; Minimal change disease (MCD), focal segmental glomeruloscelrosis (FSGS) and membranous nephropathy (MN)

Question 4

What are causes of secondary nephrotic syndrome?

Answer 4

SLE, post-infectious (group A B-haemolytic streptococcus, syphilis, malaria, TB, varicella, hepatitis B, HIV, EBV), collagen vascular disease, HSP, hereditary nephritis (Alport syndrome), sickle cell disease

Question 5

What is the pathophysiology of nephrotic syndrome?

Answer 5

Proteinuria: Structural damage to the glomerular membrane and reduction of its negatively charged componenets prevent the action of repelling negatively charged proteins, which are therefore excreted in excess.

Hypoalbuminaemia: Secondary to proteinuria and increase breakdown of albumin in the kidney.

Oedema: Hypoalbuminuria leads to decreased intravascular colloid osmotic pressure.

Question 6

Summarise the epidemiology of nephrotic syndrome.

Answer 6

Developed countries: 2-7/100,000/year (UK). MCD is the cause of nephrotic syndrome in 90% of children; most common in boys < 5 years; Peak age: 2-4 years

Developing countries: Infectious cause of GN: malaria (40%), HBV infection (6%) and group A B-haemolytic streptococcal infection (rare)

Question 7

What are signs and symptoms of nephrotic syndrome?

Answer 7

General: Anorexia, lethargy, oliguria, hypertension GI: Diarrhoea, poor feeding, abdominal pain.

Oedema: Swelling of face, ascites, oedema of legs/scrotum Symptoms of complications: Infectious, renal vein thrombosis, loin pain, haematuria.

Question 8

What are investigations for nephrotic syndrome?

Answer 8

Bloods: U&E, decrease albumin, increase ESR/CRP, lipid profile (secondary hyperlipidaemia).

Post-infectious nephropathy: Plasmodium falciparum (thick and thin blood films), ASOT, HBV/EBV/HIV serology, HIV, PCR.

Urine dipstick: 3/4 + protein, microscopic haematuria

MSU: MC&S

24-hour urine collection: Creatinine clearance and 24-hour protein excretion

Renal USS: Other renal diseases may cause proteinuria, e.g. Polycystic kidney disease

Renal biopsy: Reserved for older children with haematuria, increase BP, renal impairment, steroid-resistant patients

Doppler USS, renal angiogram, CT, MRI: If renal thrombosis is suspected

Question 9

How is nephrotic syndrome treated symptomatically?

Answer 9

Limit oedema with low-sodium diet and diuretics

Question 10

What should be monitored when treating nephrotic syndrome?

Answer 10

BP, U&E, Ca2+, weight, fluid balance

Question 11

How should the initial presentation of nephrotic syndrome be treated?

Answer 11

Longer duration (6 months) of initial prednisolone treatment is associated with fewer relapses and lower total prednisolone dose over the first 2 years

Question 12

How should a relapse of nephrotic syndrome be treated?

Answer 12

Prednisolone daily unit in remission, then a slow gradual reduction of dosage

Question 13

How should steroid-resistant patients be treated?

Answer 13

Alternate-day prednisolone with long-term cyclosporine or cyclophosphamide. Steroid-sensitive patients (85-90% cases) respond after 4 weeks, steroid-resistant (10-15% cases) have no remission after 4 weeks

Question 14

How should hypertension in nephrotic syndrome patients be treated?

Answer 14

ACE inhibitors are drug of choice

Question 15

How should complications in nephrotic syndrome be treated?

Answer 15

Penicillin prophylaxis to prevent pneumococcal peritonitis and septicaemia, mobilisation/TED stockings to prevent thrombosis.

Question 16

What are complications associated with nephrotic syndrome?

Answer 16

Renal failure: Secondary to hypovolaemia, diuretics or renal vein thrombosis.

Increase infection susceptibility: Peritonitits, pneumococcal infections due to urinary loss of immunoglobulin.

Hypercoagulability: Renal vein thrombosis and DVT secondary to hypovolaemia, urinary loss of antithrombin III, protein C and S, increase synthesis of fibrinogen in the liver, immobility secondary to leg oedema and steroid therapy.

Hyperlipidaemia: Increase synthesis of triglyceride and cholesterol with albumin in liver.

Question 17

What is the prognosis of nephrotic syndrome?

Answer 17

Before the introduction of steroids, 60% of children with the relapsing form of nephrotic syndrome died.

Steroids have revolutionised the prognosis of this condition but prognosis is affected by complications and S/E of treatment.