Lecture 18 Glomerular Disease- Clinical

Question 1

Define glomerulonephritis

Answer 1

Immune-mediated disorders that affect the glomeruli

Question 2

Name the main features of Glomerulonephritis

Answer 2

• Haematuria (non-visible or visible)
• Proteinuria (low grade or nephrotic)
• Hypertension
• Renal impairment

Question 3

Define a Nephritic State

Answer 3

• Loss of blood
Active urine sediment: haematuria, dysmorphic RBCs, cellular casts
• Hypertension- salt and water retention and vasoactive hormone release
• Renal impairment
• Inflammation disrupting GBM= haematuria (cola-coloured urine)
• Reduced GFR

Question 4

Define a Nephrotic State

Answer 4

Loss of protein
• Oedema
• Increase in hydrostatic pressure in the capillaries
• Nephrotic range proteinuria: >3.5g/day or 350mg/mmol creatinine
• Hypoalbuminemia: serum albumin <35g/L-
• Dyslipidemia

Question 5

Define the term diffuse in terms of pathology

Answer 5

> 50% of glomeruli affected

Question 6

Define Focal in term of pathology

Answer 6

<50% of glomeruli affected

Question 7

Define global in terms of pathology

Answer 7

All glomerulus affected

Question 8

Define segmental in term of pathology

Answer 8

Part of the glomerulus affected

Question 9

Name non-proliferative glomerulonephritis

Answer 9

Minimal change disease
Membranous nephropathy
FSGS

Question 10

Name proliferative glomerulonephritis

Answer 10

Mesangioproliferative GN
Membranoproliferative GN
Diffuse proliferative GN
Crescentic GN

Question 11

Are Nephritic syndrome proliferative or non proliferative

Answer 11

Proliferative

Question 12

is IgA nephropathy Nephrotic or nephritic

Answer 12

Nephritic

Question 13

How does IgA Nephropathy cause haematuria

Answer 13

• IgA is stuck within the mesanagium and does not get filtered t the urine and it becomes clogged
• IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix

Question 14

What is post infectious glomerulonephritis

Answer 14

• Follows 10-21 days after infection typically of throat or skin.
• Most commonly with Lancefield group A Streptococci.

Question 15

How is post infectious glomerulonephritis treated

Answer 15

– Antibiotics for infection, debatable.
– Loop diuretics such as frusemide for oedema (if there is oedema).
– Anti-hypertensives e.g. vasodilator drugs.

Question 16

Name 3 causes of crescentic glomerulonephritis

Answer 16

ANCA-associated
Anti-GBM
IgA vasculitis
POst infection glomerulonephritis
SLE

Question 17

What are the 3 main types of ANCA-asscoaued glomerulonephritis

Answer 17

1. Microscopic polyangiitis.
2. Granulomatosis with polyangiitis.
3. Eosinophilic granulomatosis with polyangiitis

Question 18

What is Anti-GBM disease

Answer 18

rare crescentic glomerulonephritis

Question 19

What is Good Pasture’s syndrome

Answer 19

Nephritis + lung haemorrhage

Question 20

How is anti-GBM treated

Answer 20

aggressive immunesuppression: steroid, plasma exchange, and cyclophosphamide.

Question 21

Name 3 causes of Nephrotic syndrome (non-proliferative)

Answer 21

• Minimal change disease
• Focal and segmental glomerulonephritis
• Membranous Nephropathy

Question 22

What is the general management of Nephrotic syndrome

Answer 22

• 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.

Question 23

Minimal change disease is commonly seen in what age group

Answer 23

Children

Question 24

What are the clinical features of minimal change disease

Answer 24

• Sudden onset of oedema – days.
• Complete loss of proteinuria with steroids.
• Relapse occurs in two thirds of patients.

Question 25

How is minimal change disease treated

Answer 25

* Prednisolone – 1mg/kg for up to 16 weeks. | * Once remission achieved , slow taper over 6 months.

Question 26

If there is an initial relapse in minimal change disease how is that treated

Answer 26

• Initial relapse treated with further steroid course.

Question 27

If there are subsequent relapses in minimal change disease how is that treated

Answer 27

* Cyclophosphamide * Cyclosporin- immunosuppression (calcineurin inhibitor) * Tacrolimus- immunosuppression (calcineurin inhibitor) * Mycophenolate mofetil (Anti-proliferative) * Rituximab (depleting agent)

Question 28

What is the prognosis for minimal change disease

Answer 28

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

Question 29

What is focal and segmental Glomerulosclerosis

Answer 29

* Presents with nephrotic syndrome. | * Pathology reveals focal and segmental sclerosis with distinctive patterns

Question 30

What are the distinctive patterns of focal and segmental Glomerulosclerosis

Answer 30

• tip lesion, collapsing, cellular, perihilar

Question 31

What is the prognosis of focal and segmental Glomerulosclerosis

Answer 31

* Generally steroid resistant. | * High chance of progression to end stage kidney disease.

Question 32

How is focal and segmental Glomerulosclerosis treated

Answer 32

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

Question 33

What is membranous nephropathy

Answer 33

* Commonest cause of nephrotic syndrome in adults. * IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine * IgG is too big to be filtered into urine, but IgG activates complement (C3), which punches holes in filter * Leaky filter now allows albumin to be filtered into urine  nephrotic syndrome

Question 34

What is the treatment for membranous nephropathy

Answer 34

* 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. * Immunesuppression if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function. * Cyclophosphamide and steroids (alternate months) for 6 months. * Tacrolimus. * Rituximab.