Glomerulonephritis

Question 1

Definition of Glomerulonephritis

Answer 1

renal disease characterised by inflammation and damage to the glomeruli. This allows protein (+/- blood) to leak out into the urine.

Question 2

Pathogenesis of GN

Answer 2

Humoral (antibody-mediated) or Cell-mediated (T-cells)

Question 3

Consequences of GN

Answer 3

• Damage to the glomerulus restricts blood flow, leading to compensatory rise in BP
• Damage to the filtration mechanism allows protein and blood to enter urine
• Loss of usual filtration capacity leads to acute kidney injury

Question 4

Patients clinical presentation may include:

Answer 4

• Blood pressure, normal to malignant
• Urine Dipstick: proteinuria mild í nephrotic; haematuria mild í macroscopic (nephritic)
• Renal function: normal to severe impairment

Question 5

GN is generally categorised into:

Answer 5

proliferative (nephritic) or non-proliferative (nephrotic).

Question 6

Nephrotic GN =

Answer 6

Damage to Basement Membrane and slit processes of Podocytes (barrier to plasma proteins) > non-proliferative lesion

Question 7

Nephritic GN =

Answer 7

Damage to Glomerular Capillary Endothelium or mesangial cells (barrier to red blood cells) > proliferative lesion

Question 8

Classification of GN:

Answer 8

• 1st degree - Idiopathic = the majority
• 2nd degree - Infections, Drugs, malignancies or systemic disease (e.g. ANCA associated vasculitis, Lupus, Goodpastures, Heinloch Schonelin Purpura)

Question 9

Why is diagnosing the pattern of GN so important?

Answer 9

Outcome and treatment depend on the subtype

Question 10

Nephrotic Syndrome Signs:

Answer 10

PHOHN

• PrOteinuria (>3g/day) - urine looks frothy
• Hypoalbuminaemia - albumin lost in urine (<30, gaps in podocytes allow this)
• Oedema - albumin lost in urine causes decrease in intravascular oncotic pressure. Fluid moves out to surrounding tissues.
• Hyperlipidaemia - hypoalbumnaemia cause liver to compensate production, which also leads to more production of lipids
• Often normal renal function

Question 11

Complications of Nephrotic syndrome:

Answer 11

Infections (loss of antibodies in urine)
Thromboembolism
Hyperlipidaemia

Question 12

Primary causes of nephrotic syndrome:

Answer 12

Minimal Change Glomerulonephritis
Focal Segmental Glomerulosclerosis
Membranous Glomerulonephritis

Question 13

Secondary causes of nephrotic syndrome:

Answer 13

SLE
HepB + C
HIV
DM
Malignancy

Question 14

Nephritic Syndrome Signs:

Answer 14

PHAROH

• Proteinuria - increases a small amount
• Haematuria - micro or macroscopic. Occurs due to podocytes developing large pores which allows blood and protein to escape into urine. Red Cell casts (form in nephrons and indicate glomerular damage).
• Acute Renal Failure - Low urine volume (<300 ml/day OLIGURIA)
• Red blood cell casts
• Oedema/ fluid retention
• Hypertension - often mild

Question 15

Primary causes of Nephritic syndrome:

Answer 15

IgA Nephropathy (day or two post URTI)
Rapidly Progressive GN (crescentic - Goodpasture's, Vasculitis, SLE, HSP)

Question 16

General Treatment for GN

Answer 16

Non-Immunosuppressive (ACEi/ARBs, Statins, Anticoagulants, Omega3)
Immunosuppressive (Pred > cyclophosphamide)

Question 17

Aim fo treatment are to ….

Answer 17

Induce sustained remission:

• complete = proteinuria (<300mg/day)
• Partial = <3g/day

Question 18

Minimal Change Nephropathy

Answer 18

• Most common cause of nephrotic syndrome in children (77%)
• IL-13 = possible cause
• 94% complete remission with oral steroids (2nd line cyclophosphamide)
• Does NOT cause progressive renal failure

Question 19

FSGS - Focal Segmental Glomerulosclerosis

Answer 19

• Commonest cause of nephrotic syndrome in adults (35%)
• 50% progress to ESRF after 10 years
• 60% remission with prolonged steroids

Question 20

Membranous Nephropathy

Answer 20

• 2nd commonest nephrotic syndrome in adults (15-30%
• Secondary causes = infections, connective tissue disease, malignancies
• Biopsy: Sub-epithelial immune complex deposition in the basement membrane (thickened)
• Anti PLA2r antibody (>70%)
• 30% progress to end stage renal failure in 10 years

Question 21

IgA Nephropathy

Answer 21

• Most common GN
• Asymptomatic Haematuria
• Macroscopic haematuria after resp/GI infection
• AKI/CKD
• Associated with Henoch Schonlein Purpura
• Biopsy: Mesangial cell proliferation with IgA deposits in mesangium
• 25% progress to ESRF in 10-30 years
• BP control, ACEi/ARBs, Fish oil

Question 22

Rapidly Progressive GN (RPGN)

Answer 22

• Associated with glomerular crescents on biopsy
• ANCA +ve = Systemic vasculitis, GPA, Microscopic Polyangitis
• ANCA -ve = Goodpasture’s, Heinloch Scholein Purpura, SLE
• Prompt strong immunosuppression with supportive care (may include dialysis)
• Immunosuppression = steroids (pred), Cytotoxic (cyclophosphamide)