Nephrotic Syndrome

Question 1

What are the key clinical symptoms of nephrotic syndrome?

Answer 1

Hypoalbuminaemia

• increased catabolism of reabsorbed albumin in PCT
• albuminuria (prevent using ACE inhibitors)

Proteinuria

Hyperlipidaemia caused by hypoalbuminaemia (increased synthesis of lipoproteins)

Oedema caused by hypoalbuminaemia (peri-orbital, face, arms, ascites)

Hypoalbuminaemia + proteinuria = frothy urine

Question 2

What is the general management of nephrotic syndrome?

Answer 2

Dietary sodium restriction + thiazide diuretic

Normal protein intake

Albumin infusion

Prevention of complications (DVT, sepsis, hypercholesterolaemia):

• prophylactic anticoagulation
• pneumococcal vaccine(s)
• statins
• ACE inhibitors/angiotensin II receptor antagonists

Question 3

What are some kidney-specific causes of nephrotic syndrome?

Answer 3

Minimal-change nephropathy:

• only abnormality on histology is fusion of podocytes (non-specific; indicates proteinuria)
• common in children
• does not cause CKD
• high dose corticosteroids required

Focal segmental glomerulosclerosis:

• circulating permeability factor
• segmental glomerulosclerosis —> global sclerosis
• focal tubular atrophy + interstitial fibrosis

Membranous glomerulopathy:

• 40% develop CKD
• primary (idiopathic) or secondary (drugs, autoimmune disease, neoplasia, etc.)
• uniform granular capillary wall IgG deposits and complement C3
• spiky appearance on silver-stain (deposits encircled by basement membrane)
• corticosteroids/chemotherapy required

Question 4

What are some examples of conditions which affect the kidneys and also cause cardiac impairment/failure?

Answer 4

SLE

Diabetes

Amyloidosis (myeloma)

• eosinophilic deposits (pink with Congo Red, green under polarised light)
• depletion of podocytes
• AL amyloid = light chains; AA amyloid = secondary to chronic inflammatory diseases/chronic infections
• renal biopsy required
• chemotherapy/stem cell transplant required to reduce production of protein causing amyloid formation

Question 5

What are some differentials for AKI?

Answer 5

Pre-renal e.g. hypotension

ATN

Intrinsic renal disease e.g. renal amyloid deposition

Obstruction

Question 6

Give some examples of causes of generalised oedema.

Answer 6

Renal failure (inability to remove excess salt and water) 
- check urea and electrolytes

Disorder in Starling’s equilibrium

• heart failure (increased capillary pressure; ECG and echocardiogram)
• reduced colloid oncotic pressure e.g. liver disease (LFTs, ultrasound), nephrotic syndrome (?proteinuria, serum albumin)
• increased protein permeability (inflammation) —> increased interstitial protein concentration

note: vasodilatation and increased venous pressure only causes leg oedema
note: interruption of lymphatic drainage only causes localised oedema

Question 7

Give some examples of causes of haematuria.

Answer 7

• UTI (microscopic haematuria)
• STI
• benign prostatic hypertrophy
• prostate cancer
• bladder cancer (microscopic haematuria)
• renal cell carcinoma (microscopic haematuria)
• nephritic syndromes (microscopic and macroscopic haematuria)
• trauma
• renal calculi (microscopic haematuria)
• polycystic kidneys

Question 8

What features in the brain confirm cerebral oedema postmortem?

Answer 8

Reduced depth of sulci

Reduced size of ventricles

Areas of bleeding (brain sheared by foramen magnum)

Question 9

Why does cerebral oedema cause hypertension and bradycardia?

Answer 9

Cerebral oedema compresses blood vessels —> inflammation —> increased oedema —> coning —> cardio centres affected —> Cushing’s reflex

Question 10

Give some examples of biochemical markers which may indicate the cause of nephrotic syndrome.

Answer 10

ANCA = vasculitis

anti-GBM antibodies = Goodpasture’s disease

IgA = IgA nephropathy

AL or AA = amyloidosis

Red urine

• rhabdomyolysis
• haematuria
• myoglobulinuria

Question 11

How is Goodpasture’s syndrome diagnosed histologically?

Answer 11

Add radiolabelled IgG antigens —> smooth, diffuse, linear staining (“crushed ribbon” appearance) on glomerular basement membrane

Question 12

Why does Goodpasture’s disease affect the kidneys and the lungs?

Answer 12

anti-GBM antibodies bind to the alpha-3 chain of type IV collagen, which is present in alveoli and the glomerular basement membrane

• –> rapidly progressive glomerulonephritis
• –> pulmonary haemorrhages

Question 13

What is the treatment for Goodpasture’s disease?

Answer 13

Plasmapheresis (remove autoantibodies and IgG, then return plasma)

Plasma exchange (replace plasma)

Immunosuppressant therapy

Question 14

Contrast nephrotic and nephritic syndrome.

Answer 14

NEPHROTIC = hypoalbuminaemia, oedema, proteinuria, hyperlipidaemia

NEPHRITIC = haematuria, not as severe proteinuria