Nephrotic Syndrome

Question 1

Define Nephrotic Syndrome

Answer 1

Characterised by the presence of proteinuria, hypoalbuminaemia and peripheral oedema

Proteinuria = >3.5 g/24 hours
Hypoalbuminaemia = <30 g/L

Question 2

Aetiology of Nephrotic Syndrome

Answer 2

Can be caused by various renal diseases:
Minimal change 
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis

other:
Diabetes Mellitus
Sickle cell disease
Amyloidosis 
Malignancies (lung and GI adenocarcinomas)
Drugs e.g. NSAIDs
Alport's syndrome
HIV infection

Question 3

Describe Minimal Change disease (epidemiology, symptoms, investigations, treatment, prognosis)

Answer 3

Most common cause of nephrotic syndrome in children

Presents as swelling and frothy urine

There is normal glomerular appearance on light microscopy (hence the name), but abnormal on electron microscopy
No renal biopsy is required in children

Most children (>90%) respond to corticosteroids
In adults, there is a lower response and slower response. Relapses are common
Rarely will progress to end-stage renal failure

Question 4

Describe Focal segmental glomerulosclerosis (epidemiology, aetiology, treatment, prognosis)

Answer 4

Most common cause in adults (35%), particularly Afro-Caribbeans
Can be primary or secondary (heroin use, HIV, sickle cell disease )

Poor response to corticosteroids, often requires other immunosuppresants

Rule of thirds: 1/3 recover, 1/3 respond to medication, 1/3 progress to end-stage renal failure

Question 5

Describe membranous nephropathy (epidemiology, aetiology, treatment, prognosis)

Answer 5

Second most common cause in adults, most common cause in caucasians
Can be primary or secondary (infections, malignancy, autoimmune disease, drugs)

Often requires other immunosuppressants due to poor response to corticosteroids

33% develop end-stage renal failure within 20 years

Question 6

Describe Membranoproliferative glomerulonephritis (aetiology, treatment, prognosis)

Answer 6

Can present as nephrotic (60%), nephritic (30%), or rapidly progressive glomerulonephritis.
Most common in elderly people
Associated with malignancy, SLE, infection

Poor response to corticosteroids
40% develop end-stage renal failure within 20 years

Question 7

General symptoms of Nephrotic syndrome

Answer 7

Swelling of face, abdomen, limbs, genitalia
Weight gain due to oedema
Symptoms of the underlying cause
- Occult malignancy (e.g., cough, weight loss, night sweats, or tarry stools)
- SLE (e.g., rash, photosensitivity, or arthralgias)
- Fabry’s disease (e.g., painful neuropathy).

Symptoms of complications e.g. renal vein thrombosis -> loin pain, haematuria

Question 8

Signs of Nephrotic syndrome on examination

Answer 8

Oedema: periorbital, peripheral, genital, entire body (anasarca)
Ascites: fluid thrill, shifting dullness
White banding of the nails from hypoalbuminaemia (known as Muehrcke’s lines)
Xanthelasma or xanthomata

Cause:

• Rash (consistent with SLE)
• Easy bruising and neuropathy (amyloidosis)
• Haem-positive stool (consistent with GI malignancy)
• Diabetic retinopathy on fundoscopy

Question 9

Investigations for Nephrotic syndrome

Answer 9

24h urine collection
Spot urine protein:creatinine ratio
Urinalysis: ?clasts

Albumin: Hypoalbuminaemia 
Test for cause:
 - ANA/ds-DNA: ? SLE 
 - Serology: ?HBV
 - Blood film: ? malaria 
 - ASO titre: ?group A beta-haemolytic strep 
 - c-ANCA: ? GwP

Doppler USS: ?thrombosis

Biopsy: determine type of children

Question 10

What clues in the history may indicate the cause of nephrotic syndrome

Answer 10

Minimal change glomerulonephritis - frothy urine + swelling in CHILDREN

Focal segmental glomerulosclerosis - heroin use, HIV, sickle cell

Membranous nephropathy - infections, malignancy, autoimmune disease, drugs

Membranoproliferative glomerulonephritis - ELDERLY