Glomerular disease - glomerulonephritis

Question 1

What % of end stage renal disease is caused by glomerulonephritis?

Answer 1

30%

Question 2

What is glomerulonephritis?

Answer 2

Group of disorders causing injury to the glomeruli

Question 3

What are the 4 main clinical features of glomerulonephritis?

Answer 3

• Haematuria
• Proteinuria
• Hypertension
• Renal insufficiency

Question 4

Describe the 2 types of haematuria

Answer 4

• Macroscopic - tea- or cola coloured or frank blood

* Microscopic - >5 RBC per high power field

Question 5

In which syndrome is haematuria most commonly seen in - nephritic or nephrotic syndrome?

Answer 5

Nephritic > nephrotic

Question 6

Where can the blood causing haematuria come from?

Answer 6

kidney, ureter, bladder, prostate, urethra

Question 7

Describe the haematuria seen in glomerulonephritis

Answer 7

In glomerulonephritis: persistent microscopic haematuria, microscopy shows dysmorphic RBC (Mickey-mouse-like)

Question 8

In which syndrome is proteinuria most commonly seen in - nephritic or nephrotic syndrome?

Answer 8

Presents equally in Nephritis and nephrosis

Question 9

Describe the proteinuria seen in glomerulonephritis

Answer 9

In glomerulonephritis: persistent, proteinuria of more than 1 gram /mmol creatinine

Question 10

Define hypertension

Answer 10

> 140/80 mmHg

Question 11

In which syndrome is hypertension most commonly seen in - nephritic or nephrotic syndrome?

Answer 11

Nephritic > nephrotic

Question 12

Describe nephritic state

Answer 12

Caused by inflammation of the glomeruli; involves:

o Active urine sediment: haematuria, dysmorphic RBCs, cellular casts
o Hypertension
o Renal impairment

Question 13

Describe nephrotic syndrome

Answer 13

Collection of symptoms associated with kidney damage:
o	Oedema
o	Proteinuria >3.5 g/day
o	Hypoalbuminemia
o	Hyperlipidemia

Can be caused by primary (idiopathic) glomerular disease or secondary glomerular diseases

Question 14

What are the differential diagnoses of nephrotic syndrome?

Answer 14

• Congestive Heart Failure (JVP raised, normal albumin, minimal proteinuria)
• Hepatic Disease (abnormal LFTs, no proteinuria)

Question 15

What are the 2 main classifications of glomerulonephritis?

Answer 15

• Proliferative glomerulonephritis - Excessive numbers of cells in glomeruli. These include infiltrating leucocytes
• Non-proliferative glomerulonephritis - Glomeruli look normal or have areas of scarring. They have normal numbers of cells

Question 16

Describe diffuse glomerulonephritis

Answer 16

• Diffuse: >50% of glomeruli affected

Question 17

Describe focal glomerulonephritis

Answer 17

• Focal: <50% of glomeruli affected

Question 18

Describe global glomerulonephritis

Answer 18

• Global: all the glomerulus affected

Question 19

Describe segmental glomerulonephritis

Answer 19

• Segmental: part of the glomerulus affected

Question 20

What types of glomerulonephritis are associated with nephrotic syndrome?

Answer 20

• Minimal change disease

* Membranous nephropathy

Question 21

What type of glomerulonephritis is associated with urinary sediment abnormalities?

Answer 21

IgA nephropathy

Question 22

What type of glomerulonephritis is associated with proteinuria?

Answer 22

IgA nephropathy

Question 23

What types of glomerulonephritis are associated with nephritic state?

Answer 23

• Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis
• Post-infection glomerlunephritis

Question 24

Give 4 examples of proliferative glomerulonephritis

Answer 24

• Diffuse proliferative - post-infective nephritis
• Focal proliferative - mesangial IgA disease
• Focal necrotizing (crescentic) nephritis
• Membrano-proliferative nephritis

Question 25

Describe the histopathology of Post-Infective Glomerulonephritis

Answer 25

* Global and diffuse enlarged hypercellular glomeruli * Proliferation of endothelial and mesangial cells * Infiltration of leukocytes (neutrophils and monocytes) * Crescent formation in severe cases * Red cell casts

Question 26

Describe how Post-streptococcal glomerulonephritis presents and what causes it

Answer 26

Follows 10-21 days after strep infection; typically of throat or skin. Most commonly with Lancefield group A Streptococci. Genetic predisposition: HLA-DR, -DP, -DP. ``` Produces nephritic syndrome: o Haematuria o Oliguria o Uraemia o Hypertension o Mild proteinaemia ```

Question 27

How is Post infective glomerulonephritis treated?

Answer 27

* Antibiotics for infection, debatable. * Loop diuretics such as frusemide for oedema * Vasodilator drugs (e.g. amlodipine) for hypertension

Question 28

What is the most common cause of glomerulonephritis worldwide?

Answer 28

IgA nephropathy

Question 29

Describe IgA nephropathy

Answer 29

* Commonest cause of glomerulonephritis worldwide. * Initially described in 1960s by Berger and Hinglais. * Characterized by IgA deposition in the mesangium + mesangial proliferation and depositon of matrix * Most common in 2nd and 3rd decade of life with males more commonly affected. * Up to 40% of cases can progress to end stage kidney disease

Question 30

What age group and sex is more at risk of IgA nephropathy?

Answer 30

• Most common in 2nd and 3rd decade of life with males more commonly affected.

Question 31

What % of those with IgA nephropathy progress to end stage renal disease?

Answer 31

40%

Question 32

How do those with IgA nephropathy present?

Answer 32

* Microscopic haematuria. * Micoscopic haematuria + proteinuria * Nephrotic syndrome * IgA crescentic glomerulonephritis

Question 33

What can cause crescentic glomerulonephritis?

Answer 33

Anti-neutrophil cytoplasmic antibody associated conditions e.g. Wegeners/granulomatosis associated with polyangitis Anti-glomerular basement membrane (anti GBM) disease IgA vasculitis Post infective glomerulonephritis SLE

Question 34

What % of crescentic glomerulonephritis cases are caused by anti-GBM disease?

Answer 34

10-20%

Question 35

How is anti-GBM disease treated?

Answer 35

``` Treatment is aggressive immunosuppression: o Corticosteroids o Plasma exchange o Cytotoxics e.g. Cyclophosphamide o B-cell therapy e.g. Rituximab o Complement inhibitors ```

Question 36

What is the prognosis for those with anti-GBM disease?

Answer 36

Prognosis is good provided treatment is started early enough

Question 37

Describe the features of proliferative glomerulonephritis syndromes

Answer 37

* Present with nephritic syndrome * Blood on dipstix – variable proteinuria * Can cause rapid decline in renal function leading to dialysis * Early diagnosis and appropriate treatment

Question 38

Give examples of non-proliferative glomerulonephritis

Answer 38

* Minimal Change Disease * Focal and segmental glomerulonephritis * Membranous Nephropathy

Question 39

Hw is nephrotic syndrome managed?

Answer 39

General measures • 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 towards cause of the non-proliferative glomerulonephritis

Question 40

What group of glomerulonephritis is associated with nephrotic syndrome?

Answer 40

Non-proliferative

Question 41

What is the most common form of glomerulonephritis in children?

Answer 41

Minimal change nephrotic syndrome

Question 42

Describe Minimal change nephrotic syndrome

Answer 42

* Commonest form in children * Sudden onset of oedema - days * Significant proteinuria (++++) - treat with steroids * Two thirds of patients relapse

Question 43

How is minimal change nephrotic syndrome treated?

Answer 43

Prednisolone – 1mg/kg for up to 16 weeks. Once remission achieved, slow taper over 6 months. Initial relapse treated with further steroid course. ``` Subsequent relapses treated with: • Cyclophosphamide • Cyclosporin • Tacrolimus • Mycophenolate mofetil • Rituximab ```

Question 44

What is the prognosis for those with minimal change nephrotic syndrome?

Answer 44

* Despite relapsing behaviour, prognosis is favourable. * Risk of end stage kidney disease is low. * Steroids toxicity more prevalent following multiple exposure.

Question 45

How should those with minimal change nephrotic syndrome be managed initially?

Answer 45

* Salt and fluid restrictions. * Daily weights. * Loop diuretic e.g. Furosemide. * Thromboprophylaxis e.g. low molecular weight heparin.

Question 46

How does focal and segmental glomerulonephritis present?

Answer 46

Nephrotic syndrome

Question 47

Describe the clinical features of focal and segmental glomerulonephritis

Answer 47

Is not a single disease, rather a syndrome with multiple causes that presents with nephrotic syndrome. Pathology reveals focal and segmental sclerosis with distinctive patterns e.g. tip lesion, collapsing, cellular, perihilar, and not otherwise specified Primary (idiopathic) or secondary. Generally steroid resistant. High chance of progression to end stage kidney disease. * Collapse of capillary loops * Increase in matrix and hyalinosis * Lipid droplets and foam cells in sclerotic areas

Question 48

How is Focal and segmental glomerulonephritis treated?

Answer 48

* General measures, as previously described. * Trail of steroids, positive response, even partial remission, carries better prognosis. * Alternative options: cyclosporin, cyclophosphamide, and Rituximab

Question 49

What is the commonest cause of nephrotic syndrome?

Answer 49

Membraneous nephropathy

Question 50

What serological markers indicate membraneous glomerulonephritis?

Answer 50

* Anti-phospholipase A2 receptor (PLA2R) antibody - positive in 70% of idiopathic cases * Thrombospondin type 1 domain containing 7A (THSD7A).

Question 51

What causes membraneous glomerulonephritis?

Answer 51

Majority of cases occur in isolation (idiopathic). ``` Secondary causes include: • Malignancies • SLE • Rheumatoid arthritis. • Drugs: NSAIDs, gold, penicillamine. ```

Question 52

Describe the histopathology of membraneous glomerulonephritis

Answer 52

* Spikes surround deposits * Thick GBM in relation to tubular basement membrane * Mesangial expansion

Question 53

How is membraneous glomerulonephritis treated?

Answer 53

* General measures for at least 6 months. * Immunosuppression if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function. * Cyclophosphamide and steroids (alternate months) for 6 months. * Cyclosporine. * Rituximab. * Resolves spontaneously in a third.

Question 54

What is the prognosis for those with membranous glomerulonephritis?

Answer 54

* Resolves spontaneously in a third. * Prognosis good in treated patients whose proteinuria resolves * About 25% are on dialysis after 10 years * Can recur in renal transplants

Question 55

Summarise the features of non-proliferative glomerulonephritis

Answer 55

* Present with nephrotic syndrome. * Renal biopsy is key investigation. * Identify cause, if possible. * General measures are important in all cases. * Specific treatment as appropriate.