Glomerulonephritis

Question 1

What is glomerulonephritis ?

Answer 1

• A group of renal diseases which cause immune-mediated disease of the kidneys affecting the glomeruli ​
• There is disruption of barrier function of the glomerular capillary due to damage to the 3 components which leads to haematuria and/or proteinuria

Question 2

What are the 3 main cells which can be damaged in glomerularnephritis ?

Answer 2

1. endothelial cells
2. mesangial cells
3. podocytes

Question 3

How does the cell which is damaged in the nephron help determine the features of the type of glomerularnephritis ?

Answer 3

• If it is damage to the mesangial or endothelial cells this leads to a proliferative lesion and red cells in urine.
• If it is damage to the podocytes this leads to a non-proliferative lesion and protein in urine

Question 4

How do the cells (referring to the 3 main ones mentioned earlier) differ in their response to being injured?

Answer 4

• Damage to podocytes results in atrophy of the podocytes which results in loss of the membrane barrier in the glomerular capillary which then allows plasma proteins in ==> proteinuria
• Damage to the mesangial cells results in chemokine release and attraction of inflammatory cells
• Damage to endothelial cells results vasculitis (inflam of blood vessels)

Question 5

Mesangial cells and endothelial cell damage presents similarly – both with haematuria, how would you decide between the two for which cell is most likely to be damaged?

Answer 5

Look at the creatinine – the creatinine in endothelial cell damage will be higher than in mesangial cell damage

Question 6

How is glomerulonephritis diagnosed ?

Answer 6

CLINICAL PRESENTATION

BLOOD TESTS

EXAMINATION of URINE

• Urinalysis - haematuria, proteinuria
• Urine microsopy - RBC (dysmorphic), RBC & granular casts, lipiduria
• Urine Protein: Creatinine Ratio / 24 hour urine - quantify proteinuria

KIDNEY BIOPSY

Question 7

What are the clinical presenting features of glomerulonephritis ?

Answer 7

• Haematuria
• Proteinuria
• Urine microscopy - dysmorphic RBC’s
• Impaired renal function - AKI, CKD
• Hypertension

Question 8

What are the 2 syndromes which different types of glomerulonephritis fall under the category of ?

Answer 8

• Nephrotic syndrome
• Nephritic syndrome

Question 9

What is nephrotic syndrome indicative of ?

Answer 9

Indicative of a non proliferative process affecting Podocytes

Question 10

What is nephritic syndrome indicative of ?

Answer 10

Indicative of a proliferative process affecting endothelial cells

Question 11

What are some of the features which may differentiate a glomerulonephritis from a disease like intersitial nephritis ?

Answer 11

• Possibly normal renal function in the GN
• Look for antibodies
• May see dysmorphic RBC’s in the GN

Question 12

How are the different types of GN classified ?

Answer 12

As primary (idiopathic)

or

Secondary caused by eg. infections or drugs associated with eg. malignancies or part of systemic disease eg. ANCA - associated systemic vasculitis, lupus, Goodpastures, HSP

Question 13

How are the different classifications of GN diagnosed ?

Answer 13

Histology:

Take a renal biopsy and then do Light Microscopy/ Immunofluorescence/ EM

Question 14

What is meant by Proliferative or non-proliferative when classifying GN?

Answer 14

Usually refers to presence or absence of proliferation of mesangial cells

Question 15

What is meant when GN is described as focal/diffuse?

Answer 15

< or > 50% glomeruli affected

Question 16

On histological classification of GN what is meant by global or segmental?

Answer 16

All or part glomerulus affected

Question 17

Describe what is meant by the descriptive term cresentric when describing GN?

Answer 17

Presence of crescents - epithelial cell extracapillary proliferation eg. rapidly progressive glomerulonephritis (RPGN) in vasculitis

Question 18

What are the principles for treatment of glomerulonephritis ?

Answer 18

• Reduce degree of proteinuria
• Induce remission of nephrotic syndrome
• Preserve long term renal function

Question 19

What is the treatment of glomerulonephritis ?

Answer 19

• Anti-hypertensive (target BP <130/80 - <125/75 if proteinuria) ACEi or ARB then add diuretic if required to control BP or nephrotic syndrome
• Statin - to reduce CVD risk
• Anticoagulants if nephrotic syndrome

Immunosuppressive therapy:

Drugs

• Corticosteroids (Prednisolone po/MethylPred IV)
• Azathioprine
• Alkylating agents (Cyclophosphamide/ Chlorambucil)

Plasmapharesis (TPE-therapeutic plasma exchange) – trying to remove the antibody causing it

Antibodies: IV Immunoglobulin - Monoclonal T or B cell Antibodies

Question 20

What is the main potential side effect of immunosuppressive therapy in the treatment of glomerulonephritis due to e.g. cyclophosphamide?

Answer 20

Infection