Session 8: Glomerular Disease - Glomerulonephritis & Diabetes Mellitus

Question 1

Answer 1

Question 2

Give the common histological pathological changes found in glomerulonephritis.

Answer 2

Subepithelial immune complexes

Increased number of mesangial cells

Fusion or destruction of podocytes

Narrowed, damaged, or leaky capillaries (endothelial damage)

Question 3

Four structures of the glomerulus that can be damaged in glomerulonephritis.

Answer 3

Capillary endothelium

Glomerular basement membrane (GBM)

Mesangial cells

Podocytes

Question 4

What is glomerulonephritis (GN)?

Answer 4

Inflammation of the glomeruli

Question 5

Clinical presentation of GN (degrees)

Answer 5

Asymptomatic haematuria and/or proteinuria

Chronic GN

Acute GN (Nephritic syndrome)

Rapidly progressive glomerulonephritis (RPGN)

Nephrotic syndrome

Question 6

Causes of asymptomatic haematuria and/or proteinuria.

Answer 6

IgA

SLE

FSGS

etc…

Question 7

Causes of chronic GN

Answer 7

IgA

SLE

Any treated GN

Question 8

Causes of nephritic syndrome

Answer 8

IgA

SLE

ANCA-vasculitis

Anti-GBM

Alport Syndrome

Question 9

Causes of RPGN

Answer 9

ANCA-Vasculitis

Anti-GBM

Post-infectious

SLE

Question 10

Causes of nephrotic syndrome

Answer 10

MCG

FSGS

Membranous glomerulonephritis

SLE

Question 11

Key differences between nephritic syndrome and nephrotic syndrome.

Answer 11

Nephritic:

Inflammation with a triad of haematuria, hypertension and reduced GFR. There is also cola-colored urine and oliguria.

Nephrotic:

Damage to podocytes causing reduction in selectivity of filtration. This leads to a triad of symptoms of proteinuria, hypoalbuminaemia and oedema. You may also see hyperlipidaemia in nephrotic syndrome.

Oedema can occur in both syndromes.

Question 12

BP and creatinine in nephrotic syndrome.

Answer 12

Usually normal.

Question 13

What is a proteinuria at above 350 mg/mmol called if it is presented without the triad of symptoms seen in nephrotic syndrome?

Answer 13

Nephrotic range proteinuria.

Question 14

Primary causes of nephrotic syndrome.

Answer 14

MCG

Membranous glomerulonephritis also called membranous nephropathy also called membranous glomerulonephropathy.

FSGS

Question 15

Secondary causes of nephrotic syndrome.

Answer 15

Diabetes

SLE

Renal amyloidosis

Question 16

What is the difference between DM and amyloidosis leading to nephrotic syndrome compared to SLE leading to nephrotic syndrome?

Answer 16

DM and Amyloidosis solely lead to nephrotic syndrome and glomerulonephritis. They are not classed as GNs.

Question 17

Managment of nephrotic syndrome.

Answer 17

Treating the triad of symptoms.

Oedema by thiazides, loop diuretics (furosemide most commonly) or spironolactone. If this doesn’t work due to the damage of the kidneys salt and fluid restrictions.

ACE-inhibitors

Might give statins for hypercholesterolaemia if there is long-term nephrotic syndrome.

Treating the underlying cause (steroids for MCD e.g.)

Question 18

Triad of nephritic syndrome.

Answer 18

Haematuria

Reduction in GFR (renal impairment/oliguria)

Hypertension

Question 19

Other clinical features found in nephritic syndrome.

Answer 19

Can cause slight proteinuria (Protein+)

The onset may be acute or rapidly progressive (Means it can be Acute GN or RPGN/Crescentic GN)

Question 20

Common causes of nephritic syndrome.

Answer 20

Anti-GBM disease (Goodpasture’s)

ANCA-associated vasculitis

IgA nephropathy (Berger’s disease)

Post-infectious associated with immune disease.

SLE

Henoch-Schönlein purpura

Question 21

Management of nephritic syndrome.

Answer 21

Blood presssure control by ACE-inhibitors or Angiotensin II receptor antagonists. Salt restriction.

Treatment if oedema arises

Immunosuppressants specific for the underlying disease.

In case of RPGN prednisolon, cyclophosphamide etc.. might be given.

Stop smoking

Dialysis

Question 22

What is ANCA-associated vasculitis?

Answer 22

EIther granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis.

Affecting small arterioles

Question 23

Why is ANCA-associated vasculitis often called a pulmonary-renal syndrome?

Answer 23

Because it commonly affects the kidneys and lungs.

Question 24

Give common systemic symptoms associated with ANCA-associated vasculitis.

Answer 24

Fatigue, arthralgia, myalgia and weight loss.

Question 25

How does vasculitis cause renal damage?

Answer 25

No immune deposits in the kidneys but rather circulating antibodies to white cells. Endothelial damage as well.

Question 26

What is anti-GBM caused by?

Answer 26

Caused by anti-bodies binding to alpha3 chain of type IV collagen in glomerular basement membrane. This leads to damage to GBM.

Question 27

Why is anti-GBM clinically important?

Answer 27

Because if it goes untreated it will **always** lead to RPGN.

Question 28

Where else might anti-GBM present complications?

Answer 28

In the lungs by antibodies binding to alpha3 chains of type 4 collagen in the alveolar basement membrane. This can lead to pulmonary haemorrhage and often occurs in smokers with pre-existing damage to the alveolar membrane.

Question 29

Common histological presentation of diabetic nephropathy.

Answer 29

Kimmelstiel-Wilson nodules (KW) Thicken GBM. Mesangial expansion.

Question 30

Why don't paediatricians see patient's with diabetic nephropathy?

Answer 30

Because children with diabetes will not present with nephropathy until later in life. It takes years for this damage to build up into something noticeable.

Question 31

Is diabetic nephropathy a glomerulonephritis?

Answer 31

No it's not an inflammatory condition. It is a **glomerulopathy.**

Question 32

Pathological changes in diabetic nephropathy. (In rough order)

Answer 32

Hyperfiltration and capillary hypertension GBM thickening Mesangial expansion Podocyte injury Glomerular sclerosis and arteriolosclerosis

Question 33

What causes the hyperfiltration and hypertrophy of the early stages of diabetic nephropathy?

Answer 33

Hyperglycaemia and glomerular hypertension. This leads to an increase in **GFR**.

Question 34

Clinical signs and symptoms in diabetic nephropathy. (In rough order)

Answer 34

1 - Hyperfiltration and hypertrophy leading to increased GFR. 2 - Latent stage where there will be normal albuminuria and some GBM thickening as well as mesangial expansion. 3 - Some microalbuminaemia (increase). Continued mesangial expansion and some sclerosis. Increased GBM thickening and some changes to podocytes. The GFR returns to normal. 4 - Overt proteinuria with a **diffuse** glomerular histopathlogical change. Systemic hypertension and a **fall** in GFR. 5 - ESRD

Question 35

How does GFR change in the different stages of diabetic nephropathy?

Answer 35

In 1-2 there is a rise in GFR. 3 - Normal GFR 4-5 Fall in GFR

Question 36

What is the first clinical sign of diabetic nephropathy?

Answer 36

Stage three with microalbuminuria. This is also associated with GBM thickening, mesangial expansion and **podocyte changes**. It is important to note that the diabetic nephropathy is still reversible at this stage

Question 37

When is diabetic nephropathy not reversible anymore?

Answer 37

When it has reached stage 4 with overt proteinuria.

Question 38

Explain overt proteinuria.

Answer 38

Drop in GFR due to mesangial expansion and sclerotic changes in the glomerulus causing reduced surface area for filtration. Systemic hypertension. Microvascular changes with hyalinosis of the arterioles that can lead to tissue ischaemia. Can lead to ESRD within 3-7 years

Question 39

Why is overt proteinuria in diabetes especially important?

Answer 39

Because the presentation of Normal/slightly low GFR and proteinuria of \<100 mg/mmol only shows mild kidney disease. This is unless the patient is diabetic. If the patient is diabetic this is much more destructive and can cause ESRD within 3-7 years.

Question 40

Diabetic nephropathy risk factors.

Answer 40

Genetic susceptibility (DM typ 1 with 1st degree relatives with DN has an 83% risk of developing it themselves, only 17% risk if no DN of relative) Ethnicity Hypertension Hyperglycaemia High level of hyperfiltration Increasing age Duration of the diabetes Smoking

Question 41

**Primary prevention** of diabetic nephropathy.

Answer 41

Tight blood glucose control keeping the glucose at \<48 mmol/mol Tight blood pressure control SGLT-2 inhibitors Not smoking + statin therapy (more associated with the vascular changes of diabetes)

Question 42

Management of microalbuminuria and overt proteinuria.

Answer 42

Inhibition of RAAS BP control Statin therapy Moderate protein intake

Question 43

Explain how inhibition of RAAS can help microalbuminuria and proteinuria.

Answer 43

Reduces the glomerular hyperfiltration The efferent arteriole is more affected.

Question 44

Explain how angiotensin II antagonists can help in microalbuminuria and proteinuria.

Answer 44

Angiotensin II leads to increased glomerular permeability to proteins. It also causes mesangial cell proliferation, mesangial matrix proliferation and efferent glomerular constriction. Antagonising all of this is preferential in diabetic nephropathy.

Question 45

Define glomerulopathy.

Answer 45

Pathology to the glomerulus

Question 46

Define glomerulonephritis.

Answer 46

Inflammation of the glomerulus