Glomerulonephritis

Question 1

What is glomerulonephritis?

Answer 1

A group of mostly autoimmune inflammatory disorders affecting the glomeruli.
Classified by morphology they are responsible for 30% of End stage Kidney Disease cases

Question 2

Other than autoimmune what can cause glomerulonephritis?

Answer 2

Infection
Malignancy
Drugs

Question 3

What are the two major syndromes associated with glomerulonephritis?

Answer 3

Nephritic Syndrome - Proliferative glomerulonephritis

Nephrotic Syndrome - Non-proliferative Glomerulonephritis

Question 4

What are the major types of Glomerulonephritis?

Answer 4

Proliferative:

• Post-infective nephritis
• IgA Nephropathy
• Focal Necrotising Crescentic Nephritis
• MEmbrano-proliferative nephritis

Non-proliferative:

• Minimal change disease
• Focal & Segmental GN
• Membranous Nephropathy

Question 5

How do we distinguish nephrotic from nephritic syndrome?

Answer 5

Nephritic syndrome involves Haematuria, proteinuria, hypertension and a low urine volume due to renal impairment.

Nephrotic syndrome involves hypoalbuminaemia, proteinuria, oedema and hyperlipidaemia. (basically glomeruli let albumin through)

Question 6

What is the distinguishing feature of Nephritic syndrome?

Answer 6

Red cell casts in the urine.

These are made by nephrons and so only appear in glomerular damage

Question 7

explain the presentation of nephrotic syndrome?

Answer 7

Hypoalbuminaemia due to leaky glomeruli
Directly causes proteinuria as albumin gets into urine
Oedema occurs because theres not enough albumin in blood to osmotically keep water from moving into the Extra-vascular compartment
Hyperlipidaemia because liver over produces albumin to compensate and produces more lipids as a side effect

Also raises risk of thrombosis and infection

Question 8

What do diffuse, focal, global and segmental mean in terms of glomerulonephritis?

Answer 8

Focal affects <50% of the glomeruli
Global affects 100%
Diffuse affects >50%

Segmental only affects specific parts of the glomerulus

Question 9

What are the types of proliferative glomerulonephritis?

Answer 9

Post-infective Nephritis (diffuse)
IgA nephropathy (Focal)
Focal Necrotising Crescentic Nephritis (FNCN)
Membrano-proliferative nephritis

Question 10

What causes post-infective nephritis?

Answer 10

Mostly group A streptococci, it occurs 10-20 days post- skin/throat infection

Associated with genetic predisposition (HLA-DR or HLA-DP)

Question 11

How do treat nephritic syndrome?

Answer 11

Amlodipine vasodilator for hypertension

Loop diuretics if theres oedema

Question 12

What is the commenest cause of glomerulonephritis worldwide?

Answer 12

IgA nephropathy.

Its most common in teens/20s & men

Question 13

Describe the pathogenesis of IgA nephropathy

Answer 13

IgA deposited in mesangium along with mesangial proliferation

Question 14

How severe is IgA nephropathy?

Answer 14

Can be very minor with just microscopic haematuria

Or very severe with IgA crescentic GN leading to kidney failure within weeks

Question 15

How does Focal Necrotising Crescentic Nephritis (FNCN) look?

Answer 15

A crescent of cells & Debris fills the bowman’s Space on biopsy.

It causes crazy high creatinine (~1200)

Question 16

What are the classes of FNCN?

Answer 16

1) ANCA associated including wegener’s & microscopic polyangiitis
2) Anti-GBM (Glomerular Basement Membrane) incl anti-GBM nephritis and goodpasture’s syndrome
3) Others e.g. IgA vasculitis, post infective or SLE

Question 17

How do you tell apart Anti-GBM FNCN

Answer 17

Anti-GBM antibodies can be found in the serum & kidney

May feature lung haemorrhage

Question 18

How do you treat Focal Necrotising Nephritis?

Answer 18

With aggresive immunosuppression:

• High dose steroids
• Cyclophosphamide
• Plasma Exchange

B Cell Therapy - Rituximab
Complement inhibitors

Question 19

What are hte types of non-proliferative glomerulonephritis?

Answer 19

1) Minimal change disease
2) Focal & Segmental GN
3) MEmbranous nephropathy

Question 20

Who is most affected by minimal change disease?

Answer 20

Its the most common form in children

Question 21

What characterises Minimal change disease?

Answer 21

Sudden onset oedema

Question 22

How do we treat minimal change disease?

Answer 22

Prednisalone

If they relapse use steroids again, concurrent relapses use other treatments like cyclophosphamide, tacrolimus or rituximab

Question 23

How do you differentiate focal & segmental GN from other non-proliferative Glomerulonephritis’?

Answer 23

Well for starters its focal so <50% of glomeruli and segmental so only affects certain parts of the glomerulus.

Question 24

How do you treat Focal &Segmental GN?

Answer 24

Trial steroids (often resistant)
Cyclosporin, cyclophosphamide & Rituximab

Question 25

Whats the commenest cause of nephrotic syndrome?

Answer 25

Membranous nephropathy in adults or Minimal change disease in kids

Question 26

What causes Membranous nephropathy?

Answer 26

Mostly idiopathic

Secondary to Malignancy, SLE, rheumatoid arthritis or drugs (NSAIDs/gold/penicillin)

Question 27

How do you tell membranous nephropathy apart?

Answer 27

Biopsy

Also primary membranous nephropathy shows serological markers (PLA2R antibodies & THSD7A)

Question 28

How do you treat membranous nephropathy?

Answer 28

Just use general anti-nephrotic syndrome treatments for the 1st 6 months as 1/3rd of cases resolve on their own.

Immunosuppression (Monthly alternation of cyclophosphamide & Steroids for 6 months)

Cyclosporin

Rituximab

Question 29

What general measures do you use to treat nephrotic syndrome?

Answer 29

Na/fluid restriction + loop diuretic for oedema
Statin for hyperlipidaemia
Pneumococcal vaccine for infection risk
Heparin/warfarin for thrombosis risk
RAAS blockage for hypertension

Question 30

In Summary:

Cases in powerpoint

Answer 30

There are two categories of glomerulonephritis:
Proliferative & Non-proliferative

They are associated with nephritic (haematuria, hypertension & renal impairment) and nephrotic syndrome (proteinuria, oedema, hypoalbuminae & hyperlipidaemia) respectively.

There are a number of causes within each category but mostly they are autoimmune in origin (barring post-infective and membranous which can be secondary to malignant, drugs, R arthritis & SLE).

Treatment revolves around solving the problems/risks associated with nephritic/nephrotic syndrome and steroids/immunosuppression with mainly cyclophosphamide.