Glomerular disease - pathology and clinical aspects

Question 1

What is Glomerulonephritis?

Answer 1

Glomerulonephritis (GN) is an umbrella term applying to a number of different conditions that cause inflammation and damage in or around the glomeruli.

This allows protein (+/- blood) to leak out into the urine.

The conditions are generally categorised into either proliferative or non-proliferative.

Question 2

Clinical features of Nephrotic syndrome (4)

Answer 2

If patient is in a nephrotic state they must have the following features:

Proteinuria > 3g in 24 hr

Peripheral oedema

Low serum albumin due to leakage

hypercholesterolaemia

Question 3

Difference between nephritic syndrome and nephrotic syndrome?

Answer 3

Nephrotic syndrome involves the loss of a lot of protein (albumin) from the urine

Whereas nephritic syndrome involves the loss of a lot of blood (and less protein). There is no set criteria for symptoms unlike that of nephrotic syndrome.

Question 4

What is proliferative glomerulonephritis

Answer 4

Excessive numbers of cells in glomeruli.

These include infiltrating leucocytes

Early diagnosis is necessary to save nephrons

Can cause rapid decline in renal function leading to dialysis.

Present with nephritic state

Question 5

What is non-proliferative glomerulonephritis

Answer 5

Glomeruli look normal or have areas of scarring - Minimal change disease

Present with nephrotic syndrome

They have normal numbers of cells

Renal biopsy is key investigation

Focal and segmental glomerulonephritis

Question 6

Descriptive terms relating to renal pathology

Answer 6

Diffuse >50% of glomeruli affected

Focal <50% of glomeruli affected

Global: all the glomerulus affected

Segmental: part of the glomerulus affected

Membraneous nephropathy

Question 7

What is IgA nephropathy/Berger’s disease?

Answer 7

Commonest cause of glomerulonephritis world-wide.

IgA antibody deposition in the mesangium (middle part of kidney between capillaries) + mesangial cell proliferation

M>F

Up to 30% of cases can progress to end stage kidney disease or halving eGFR at 10 years.

Question 8

How does IgA Nephropathy present?

Answer 8

Microscopic haematuria (non-visible)

Micoscopic haematuria + proteinuria

Nephrotic syndrome

IgA crescentic glomerulonephritis

Question 9

Post-streptococcal glomerulonephritis

Answer 9

Follows 10-21 days after infection typically of throat or skin.

Most commonly with Lancefield group A Streptococci.

Genetic predisposition: HLA-DR, -DP, -DP.

Question 10

What is Crescentic glomerulonephritis?

Answer 10

characterised by the presence of extensive glomerular crescents (usually greater than 50%) in histology

Associated with rapid decline in kidney function

Question 11

Primary or idiopathic crescentic glomerulonephritis is classified into the following types

Answer 11

Anti-neutrophil cytoplasmic antibody (ANCA)-associated

Anti-glomerular basement membrane

Others: IgA vasculitis, post-infection glomerulonephritis or SLE

Question 12

Examples of Anti-neutrophil cytoplasmic antibody associated small vessel vasculitis (ANCA)

Answer 12

Microscopic polyangiitis.

Granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis.

Question 13

What is Goodpasture syndrome/ Anti-glomerular basement membrane (GBM) disease

Answer 13

Anti GBM antibodies attack the glomerulus and the pulmonary basement membrane

So if given a case of a patient presenting with acute renal failure and haemoptysis this would be Goodpasture syndrome

Question 14

How is anti-GBM disease diagnosed?

Answer 14

Demonstrating anti-GBM antibodies in serum and kidney

Question 15

Treatment of anti GBM

Answer 15

Aggressive immunosuppression by steroid, plasma exchange, and cyclophosphamide.

Question 16

Management of nephrotic syndrome

Answer 16

General:

Treat oedema: salt and fluid restriction and loop diuretics.

Hypertension: use Renin-Angiotensin-Aldosterone-blockade.

Reduce risk of thrombosis: Heparin or Warfarin.

Reduce risk of infection e.g. pneumococcal vaccine.
Treat dyslipidemia e.g. statins.

Specific therapy - target cause

Question 17

What is Minimal change disease

Answer 17

Type of glomerulonephritis

It is the commonest cause of nephrotic syndrome. Commonest form in children.

Sudden onset of oedema, low albumin and proteinuria (days)

Responds well to treatment with steroids

Question 18

Treatment of minimal change disease

Answer 18

Prednisolone – 1mg/kg for up to 16 weeks.

Once remission achieved, slow taper over 6 months.

Question 19

Initial relapse of minimal change disease is treated with what?

Answer 19

A further steroid course

Question 20

Subsequent relapses of minimal change disease is treated with what?

Answer 20

Cyclophosphamide
Cyclosporin
Tacrolimus
Mycophenolate mofetil
Rituximab

Question 21

What does the term Focal segmental glomerulosclerosis mean?

Answer 21

Not a single disease, rather a syndrome with multiple causes. Commonest cause of nephrotic syndrome in adults.

Presents with nephrotic syndrome.

Pathology reveals focal and segmental sclerosis (scarring/damage) with distinctive patterns

Can be primary (idiopathic) or secondary

Steroid treatment

High chance of progression to end stage kidney disease

Question 22

Membranous Glomerulonephritis

Answer 22

Commonest type of glomerulonephritis overall. 2 peaks of presentation - in your 20s and 60s

70% cases are idiopathic but secondary causes include: Malignancies, Rheumatoid arthritis and medication like NSAIDs.

The glomerular basement membrane becomes thickened by IgG deposits - this activates Complement system (C3) which punches holes in the filter making it leaky. It now allows albumin to be filtered into urine => nephrotic syndrome

Serological markers
PLA2R antibody positive in 70% of idiopathic cases
(THSD7A) in ~2%.

Question 23

Treatment of membranous nephropathy

Answer 23

General measures for at least 6 months. Immunosuppression (steroids and cyclophosphamide) if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function.

Tacrolimus.

Rituximab.

Question 24

Prognosis of membranous nephropathy

Answer 24

Resolves spontaneously in a third.

Prognosis good in treated patients is proteinuria resolves

About 25% are on dialysis at 10 years

Can recur in renal transplants

Question 25

Give examples of non-proliferative glomerulonephritis

Answer 25

Minimal change disease
Focal segmental glomerulosclerosis
Membranous glomerulonephritis

Question 26

Give examples of proliferative glomerulonephritis

Answer 26

IgA nephropathy
Post infectious streptococcal
Crescentic - Rapidly progressive glomerulonephritis (think crescendo)

Question 27

Features of Nephritic syndrome

Answer 27

No set criteria of symptoms:

Haematuria

Oliguria

Proteinuria

Oedema - peripheral and pulmonary

Question 28

Aetiology of glomerulonephritis

Answer 28

Some are due to immunoglobulin deposition

Some are diseases with no immunoglobulin deposition – for example – diabetic glomerular disease

Question 29

What are mesangial cells?

Answer 29

A ‘tree-like’ group of cells that support renal capillaries.

Question 30

What are podocytes?

Answer 30

Cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus.

Podocyte cells make up the epithelial lining of the Bowman’s capsule, the third layer through which filtration of blood takes place.

Question 31

Main causes of Haematuria

Answer 31

UTI
Stone
Urinary tract Tumour

Question 32

In IgA nephropathy (type of glomerulonephritis) where does the IgA antibody get deposited? What is the result of this?

Answer 32

In the mesangium - the cells in between the capillaries. This irritates them and causes them to proliferate and produce more matrix

Question 33

Example case presentation of patient with nephrotic syndrome (ie they have specific features but the underlying cause is not clear from these)

Answer 33

50 y/o M - 3 weeks of feeling unwell and swollen legs

Blood biochemistry and haematology tests show low serum albumin and a urine dipstick test shows proteinuria.

He’s referred to see a nephrologist who measures the protein level (albumin) in his urine – very heavy loss

After diagnosis do clotting screen (prevent risk of bleeding to death) and then do a renal biopsy if okay

Question 34

Diabetes and glomerulonephritis

Answer 34

Glycated molecules cause matrix deposition in the basal lamina underlying the endothelium and in the mesangial matrix

Results in thickened but leaky glomerular basement membranes and the thickened mesangial matrix compresses capillaries

Continued poor glycaemic control causes an inevitable decline

Question 35

What is Granulomatosis with polyangiitis (formerly called Wegener’s)?

Answer 35

A rare disease of uncertain cause that can affect people of all ages. Lethal if not correctly diagnosed or treated.

It is caused by autoantibodies against proteinase 3

c-ANCA test (positive if you detect these autoantibodies)

It is characterised by vasculitis mainly in the respiratory tract and the kidneys