Glomerulonephritis

Question 1

Define glomerulonephritis [1]

Answer 1

inflammatory disease involving glomerulus and tubules

Question 2

What are the pathological mechanisms which can lead to glomerulonephritis? [7]

Answer 2

1. antibodies
2. immune complexes
3. cytokines
4. growth factors
5. complement
6. proteinuria
7. metabolic/genetic/vascular causes

Question 3

What parts of the kidney can get injured in glomerulonephritis? [6]

Answer 3

1. mesangial cells
2. epithelial cells
3. endothelial cells
4. basement membrane
5. vasculature
6. tubular structures

Question 4

What are the tests in the glomerulonephritis screen? [8]

Answer 4

1. ANCA → found in ANCA-associated vasculitis
2. Anti-GBM → found in Goodpasture’s syndrome
3. ANA/dsDNA → found in systemic lupus erythematosus
4. Complement
5. Anti-PLA2R → found in membranous nephropathy
6. Immunoglobulins → found in IgA nephropathy
7. Rheumatoid factor
8. Virology — hep B, C, HIV

Question 5

A kidney biopsy is required for the clinical diagnosis of glomerulonephritis. A biopsy of kidney cortex is examined in 3 ways. State the 3 examinations and what you look for in each [6]

Answer 5

Biopsy of kidney cortex examined under:

1. Light microscopy → glomerular and tubular structure
2. Immunofluorescence → looking for lg and complement
3. Electron microscopy → glomerular basement membrane and deposits

Question 6

Define nephrotic syndrome and list its complications [4]

Answer 6

1. nephrotic syndrome is a triad of:
   
   • proteinuria (>3g/24hrs) (urine PCR>300)
   • hypoalbuminaemia (<30g/L)
   • oedema
2. complications:
   
   • hyperlipidaemia
   • thromboembolism
   • infection

Question 7

Define nephritic syndrome (what is it typically characterised by)? [3]

Answer 7

1. hypertension
2. blood and protein in urine
3. declining kidney function

Question 8

IgA nephropathy:

1. what is it? [1]
2. causes? [4]
3. pathological characteristics? [3]
4. clinical manifestations? [3]
5. treatment? [2]

Answer 8

1. primary glomerular disease affecting the mesangial cells
2. causes:
   
   • may be precipitated by infection (synpharyngitic)
   • may be secondary to HSP, cirrhosis, coeliac disease
3. pathological characteristics:
   
   • abnormal/over-production of IgAI, IgA I/C
   • mesangial IgA, C3 deposition
   • mesangial proliferation
4. clinical manifestations:
   
   • haematuria
   • hypertension
   • proteinuria (varies with prognosis)
5. treatment:
   
   • no specific therapy
   • give antihypertensives - ACE inhibitors

Question 9

Membranous nephropathy

1. definition? [1]
2. causes? [4]
3. diagnosis: pathological features? [2]
4. features on electron microscopy? [2]
5. features on immunofluorescene? [1]
6. treatment? [3]

Answer 9

1. adult nephrotic syndrome
2. can be primary (idiopathic) or secondary (malignancy/CTD/drugs)
3. diagnosis/pathological features:
   
   • anti-phospholipase A2 receptor antibody present in 70%
   • diffusely thickened basement membrane due to subepithelial deposits of several immune complexes
   • the subepithelial deposits activate the complement system which then activates the membrane attack complex which directly damages both podocytes and mesangial cells
4. features on electron microscopy:
   
   • “spike and dome” pattern - due to thickened BM
   • effacement of the foot processes of podocytes
5. features on immunofluorescence:
   
   • granular immune complexes
6. treatment:
   
   • treat underlying disease if secondary
   • supportive treatment:
     
     • ACE inhibitors
     • statin
     • diuretics
     • salt restriction
   • specific immunotherapy
     
     • steroids
     • alkylating agents (cyclophosphamide)
     • rituximab, anti-CD20 MAb
     • cyclosporin

Question 10

Minimal change disease

1. definition? [1]
2. pathogenesis? [2]
3. treatment? [1]

Answer 10

1. nephrotic syndrome most common in children
2. T cell release cytokines that target glomerular epithelial cell (i.e. podocytes) causing damage to the podocyte’s foot processes (effacement) - however the damage isn’t as severe and only causes selective proteinuria (only allows proteins such as albumin through but not massive proteins such as immunoglobulins)
3. high dose steroids - prednisolone

Question 11

What is crescentic disease? [1]

Answer 11

1. group of conditions that demonstrate abnormal cell proliferation in the glomerulus representing a crescent shape
2. this crescent can often undergo sclerosis which ultimately leads to severe damage of the glomeruli, leading to ineffective filtration of blood (hence eGFR goes down) and it often progress to end-stage renal failure

Question 12

What are the common causes of crescentic disease? [5]

Answer 12

1. ANCA vasculitis
2. Goodpasture’s syndrome
3. Lupus nephritis
4. Infection associated
5. HSP nephritis

Question 13

What are the associated diseases of nephrotic syndrome?

1. primary causes? [3]
2. secondary causes? [5]

Answer 13

1. Primary causes
   
   • Minimal change glomerulonephritis
   • Focal segmental glomerulosclerosis
   • Membranous glomerulonephritis
2. Secondary causes
   
   • SLE
   • Hep B and C
   • HIV
   • Diabetes mellitus
   • Malignancy

Question 14

What are the associated diseases of nephritic syndrome?

Answer 14

1. Post-streptococcal glomerulonephritis
   
   • appears weeks after upper respiratory tract infection
2. IgA nephropathy
   
   • appears within a day or two after a URTI
3. Crescentic glomerulonephritis
4. Goodpasture’s syndrome
   
   • anti-GBM antibodies against basal membrane antigens
5. Vasculitic disorder
6. Membranoproliferative glomerulonephritis
   
   • primary or
   • secondary to SLE, Hepatitis B/C
7. Henoch-Schönlein purpura - systemic vasculitis
   
   • deposition of IgA in the skin and kidneys