Nephrotic Syndrome: Membranous nephropathy

Question 1

Definition

Answer 1

Immune deposition of IgG and complement components between podocytes and the glomerular basement membrane (GBM)

Question 2

Epidemiology + Risk Factors

Answer 2

Middle-aged: 40-50
Male
Secondary MG risk factors:
- Drugs
- Malignancies
- Autoimmune diseases
- Systemic infections

Question 3

Aetiology

Answer 3

Primary: Associated with numerous auto-antibodies:
- Anti-phospholipase A2 receptor (PLA2) antibodies: elevated in 70% of cases
- Neutral endopeptidase antibodies
- Cationic bovine serum albumin antibodies

Secondary:
- Drugs: NSAIDs, gold, penicillamine
- Malignancies: e.g. chronic lymphocytic leukaemia, lymphoma, prostate, lung
- Autoimmune diseases: e.g. SLE, rheumatoid arthritis, thyroiditis
- Systemic infections: hepatitis B virus, HIV, malaria, syphilis

Question 4

Pathophysiology

Answer 4

Immune deposition of IgG and complement components between podocytes and the glomerular basement membrane (GBM)
- Subsequent inflammation increases the permeability of the glomerulus, resulting in nephrotic syndrome
- ‘Membranous’ refers to thickening of the glomerular capillary walls under light microscopy

Question 5

Signs

Answer 5

Oedema
Oliguria
HTN

Question 6

Symptoms

Answer 6

Foamy urine (proteinuria)

Question 7

Diagnosis

Answer 7

Urine dipstick: proteinuria
Urine microscopy and culture: exclude UTI
U&Es: establish renal function at first presentation, monitor for deteriorating renal function and progression to ESRD
C3 levels: C3 hypocomplementaemia due to C3 depletion may be present
GOLD STANDARD: Renal biopsy: TRIAD:
- ‘Spike and dome pattern’ on electron microscopy due to GBM thickening and subepithelial electron-dense deposits
- Capillary wall thickening on light microscopy
- Fine granular, capillary loop staining for IgG with immunofluorescence

Question 8

Management

Answer 8

Primary (idiopathic) MG:
- Corticosteroids and cyclophosphamide: patients with severe or progressive disease require a 6-month course of oral cyclophosphamide and alternating monthly oral/IV corticosteroids; e.g. if urinary protein excretion >4g/day
Cyclosporin: may be considered as an alternative to corticosteroids and cyclophosphamide
Tacrolimus: may be considered as an alternative to corticosteroids and cyclophosphamide
Secondary MG:
- Treat the cause
General:
- ACE-inhibitor or ARB: offered to virtually all patients to reduce proteinuria and the rate of disease progression
- Statin: all patients with nephrotic syndrome will be evaluated and treated for dyslipidaemia
- Oral warfarin: patients with a marked reduction in serum albumin and additional risk factors for thrombosis