Clinical Aspects of Glomerular Disease (Glomerulonephritis)

Question 1

What is glomerulonephritis?

Answer 1

A group of inflammatory disorders of the kidney

Question 2

How are the different sub-types of GN classfied?

Answer 2

Via their morphology

Question 3

Describe nephrotic syndrome.

Answer 3

Massive loss of protein via urine = Hypoalbuminaemia - this is due to leaky glomeruli

Hypoalbuminaemia leads to oedema and hyperlipidaemia

Urine looks frothy

Question 4

Why does Hypoalbuminaemia cause oedema and hyperlipidaemia?

Answer 4

Oedema - loss of albumin causes a reduced intravascular oncotic pressure which causes fluid to leak out of vessels and into surrounding tissue

Hyperlipidaemia - low albumin causes liver to increase albumin production in order to compensate BUT this also leads to increased production of lipids

Question 5

Describe nephritic syndrome.

Answer 5

High levels of blood in urine
Increased levels of protein, but not as high as in nephrotic
Mild hypertension
Low urine volume due to reduced renal function

Question 6

What type of glomerulonephritis causes nephrotic syndrome?

Answer 6

Non-proliferative glomerulonephritis - such as minimal change, membranous, focal segmental and Membranoproliferative (not sure about this one)

Question 7

What type of glomerulonephritis causes nephritic syndrome?

Answer 7

Proliferative glomerulonephritis - such as:

IgA
Cresent/rapidly progressive
Post-streptococcal/post-infective

Question 8

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

Answer 8

Focal affects under 50% of the glomeruli
Diffuse affects over 50%
Global affects 100%

Segmental only affects specific parts of the glomerulus

Question 9

Differentials for nephrotic syndrome?

Answer 9

Congestive heart failure

Hepatic disease

Question 10

Name the proliferative subtypes again and name which ones are focal and which on is diffuse.

Answer 10

IgA - focal

Post Infectiive - diffuse

Crescentic/Focal necrotizing/rapidly progressive - focal

Membrano-proliferative

Question 11

Describe the presentation of post-infective GN.

Answer 11

Follows 10-21 days after infection of throat or skin

Patient will be generally unwell and have dark urine

Might have puffy face
Might have higher BP

Question 12

Most common type of bacteria causing post-infective GN?

Answer 12

Lancefield group A streptococci

Question 13

Does post-infective GN have a genetic predisposition?

Answer 13

Yes

Question 14

Treatment for post-infective GN?

Answer 14

Loop diuretics IF there is oedema - frusemide

Vasodilators for mild hypertension - amlodipine

Antibiotics are debatable

Question 15

Most commonest cause of GN ?

Answer 15

IgA nephropathy

Question 16

Pathogenesis of IgA GN?

Answer 16

IgA is depositied in mesangium causing mesangial proliferation (see Dr P Browns lecture for more)

Question 17

How will IgA present?

Answer 17

As a nephritic syndrome but with microscopic blood in urine with maybe some protein present in urine also

Question 18

IgA investigations?

Answer 18

Biopsy will show IgA deposits

Question 19

IgA GN treatment?

Answer 19

Steroids or cyclophosphamide if reduced renal function - support for transplantation

Otherwise just support symptoms, like hypertension with hypertensive therapy (ACEIs)

Question 20

What is the outcome for IgA?

Answer 20

20% ~ reach ESRD in 20 years

Question 21

Outcomes for post infective?

Answer 21

95% of children make full recovery

The rest could go on to develop crescentic/ rapid progressing GN

Question 22

Describe Cresentic GN.

Answer 22

Most aggressive type and can lead to ESRD in days

Question 23

What does crescentic look like pathology wise?

Answer 23

A crescent shape of cells fills the bowmans space

Question 24

What does crescentic GN do to creatinine levels?

Answer 24

Increases them greatly

Question 25

What is anti-GBM?

Answer 25

Anti-glomerular basement membrane also known as goodpastures A type of crescentic GN causes by anti-GBM (glomerular basement membrane)

Question 26

What % of crescentic GN is anti-GBM?

Answer 26

10-20%

Question 27

How does anti-GBM present?

Answer 27

Nephritis | Haematuria and haemoptysis

Question 28

What causes the haemoptysis in anti-GBM?

Answer 28

A CxR will show infiltrates

Question 29

How is anti-GBM diagnosed?

Answer 29

Anti-GBM antibodies in serum and kidney will be detected

Question 30

Treatment for anti-GBM?

Answer 30

Agressive immunosuppression - steroids, plasma exchange, cyclophophamide

Question 31

How is crescentic GN managed?

Answer 31

Same as anti-GBM Immunosupression

Question 32

Name some ways to immunosupress.

Answer 32

``` Steroids Cyclophosphamide Plasma exchange B-cell therapy Complement inhibitors ```

Question 33

Crescentic prognosis?

Answer 33

Good if treated early

Question 34

Summarise proliferative GN.

Answer 34

Presents with nephritic syndrome Blood on dipstix with variable proteinuria Can cause rapid decline in renal function --> dialysis Early diagnosis and treatment = good prognosis

Question 35

What actually is the main difference between proliferative and non-p?

Answer 35

P - Excessive numbers of cells in glomeruli. These include infiltrating leucocytes Non-P = Glomeruli look normal or have some areas of scarring. Normal no. of cells

Question 36

Name again the types on non-p GN?

Answer 36

Minimal change Membranous Focal and sentimental Membranoproliferative (not sure again if this is P or NP)

Question 37

How do we generally manage nephrotic syndrome?

Answer 37

Treat oedema via loop diuretics/salt and fluid restriction Treat hypertension - RAAS blockade Treat hyperlipidaemia - statins Reduce risk of thrombosis - Heparin/Warfarin Reduce risk of infection - pnumonococcal vaccines

Question 38

What is the commonest cause of nephrotic syndrome in children?

Answer 38

Minimal change GN

Question 39

Describe the onset of minimal change GN.

Answer 39

Sudden onset of oedema within days

Question 40

Treatment for minimal change GN?

Answer 40

Steroids - prednisolone until remission is achieved then slowly taper off 2/3rds of patients relapse so treat this with a further steroid course Any further relapses trat with cyclophosphamide

Question 41

Minimal change prognosis?

Answer 41

Despite replases prognosis is good and risk of ESRD is low Steroid toxicity risk is high depending on exposure

Question 42

Describe focal and segmental GN.

Answer 42

Is not a single disease but a syndrome with multiple causes Can be 1y - idiopathic - or have a 2y cause Presents with nephrotic syndrome High chance of progression to ESRD

Question 43

What does the pathology show for focal segmental GN?

Answer 43

Reveals focal and segmental sclerosis with distinctive patterns

Question 44

Is steroids a good treatment for FS GN?

Answer 44

No as it is generally resistant to steroids

Question 45

Treatment for FSGN?

Answer 45

General measures to handle symptoms - hypertension, hyperlipidaemia, oedmea, and anti-coagulants Trail steroid treatment - even if it partially works it still improves prognosis Could try cyclophosphamide, cyclosporin etc

Question 46

What is the commonest cause of nephrotic syndrome in adults?

Answer 46

Membranous nephropathy

Question 47

What causes the majority of membranous GN cases?

Answer 47

Occur in isolation - idiopathic

Question 48

What are the serological markers for membranous GN?

Answer 48

Anti-phospholipase A2 receptor antibody Thrombospondin type 1 domain containing 7A

Question 49

2y causes of membranous GN?

Answer 49

Malignancy SLE Rheumatoid arthritis Drugs - NSAIDs, gold, penicillamine

Question 50

Treatment for membranous GN?

Answer 50

General measures for ~6 months Immunosuppression if symptomatic nephrotic syndrome - rising proteinuria/deteriorating renal function Cyclophosphamide and steroids, alternate months for 6 months Cyclosporin Rituximab - b-cell therapy

Question 51

Prognosis of membranous GN?

Answer 51

Resolves in 1/3 of patients Prognosis good if treatment controls the proteinuria BUT ~25% end up on dialysis in 10 years and it can reoccur even after transplantation

Question 52

Summarize the key points for non-proliferative GN.

Answer 52

Presents as nephrotic syndrome Renal biopsy is a key investigation ID the cause and treat it if 2y General measures to control symptoms are important in all cases Specific treatment should be tailored to the type of GN