12. Diabetes, Hypertension, Systemic Diseases

Question 1

What histological features can be seen in the glomerulus of a patient with diabetic nephropathy?

Answer 1

Kimmelstiel-Wilson nodule.
Thickened GBM.
Mesangial expansion.

Question 2

What is the commonest cause of end stage renal failure? How long does this take to reach in this condition?

Answer 2

Diabetic nephropathy (glomerulopathy).
3-7 years.

Question 3

What pathological changes are seen in diabetic nephropathy?

Answer 3

Hyperfiltration/capillary hypertension.
Then
Glomerular basement membrane thickening.
Mesangial expansion.
Podocyte injury.
Glomerular sclerosis/arteriolosclerosis (hyaline in arterioles).

Question 4

Via what two channels does glucose reuptake occur in the proximal convoluted tubule?

Answer 4

Apical membrane - SGLT2.

Basolateral membrane - GLUT2.

Question 5

What causes glomerular hypertension in diabetes?

Answer 5

Upregulation of SGL2 receptors to increase reabsorption of glucose and Na+. Less salt in the macula densa stimulates renin release from granular cells, leading to glomerular hypertension.

Question 6

What happens to GFR over the progressive course of diabetic nephropathy?

Answer 6

Increased GFR with hyperfiltration and hypertrophy.
Then normal GFR with increased GBM thickening and podocyte changes.
Falling GFR with diffuse glomerular histopathological changes.

Question 7

What happens to urine protein levels over the progressive course of diabetic nephropathy?

Answer 7

Normal albuminuria.
Microalbinuria when increased GBM thickening and podocyte changes.
Overt proteinuria in dissuade glomerular histopathological changes.

Question 8

What is the first clinical sign of diabetic nephropathy?

Answer 8

Microalbuminuria.

Question 9

What would you use to measure microalbuminuria?

Answer 9

Albustix.

Question 10

What pathological change causes overt proteinuria in diabetic nephropathy?

Answer 10

Mesangial expansion/sclerosis - reduced surface area for filtration.

Question 11

What causes tissue ischaemia in diabetic nephropathy?

Answer 11

Microvascular changes such as hyalinosis of arterioles.

Question 12

Name 3 risk factors for diabetic nephropathy.

Answer 12

Genetic susceptibility.
Race.
Hypertension.
Hyperglycaemia.
High level of hyperfiltration.
Increasing age.
Duration of diabetes.
Smoking.

Question 13

What is microalbuminuria/proteinuria/raised resum creatinine associated with an increased risk of in diabetic nephropathy?

Answer 13

Increased cardiovascular risk.

Question 14

What is the first line primary prevention of diabetic nephropathy?

Answer 14

Tight blood glucose control of <48 mmol/mol - this can reverse initial hyperfiltration and delay microalbuminuria.
Tight blood pressure control and inhibition of RAAS eg statin therapy.

Question 15

What affect does increased angiotensin II have on the glomerulus in diabetic nephropathy?

Answer 15

Increased glomerular permeability to proteins.
Mesangial cell proliferation.
Increased mesangial matrix.
Efferent glomerular constriction - increasing glomerular pressure.

Question 16

What slows progression of diabetic nephropathy at stages 2-4?

Answer 16

RAAS blockade.

Question 17

What affect does a RAAS blockade have on the kidneys in diabetic nephropathy?

Answer 17

Reduced glomerular hyperfiltration.
Efferent arteriole dilation (EA>AA).
Anti-proteinuria effect more than BP alone.

Question 18

When is RAAS blockade use limited?

Answer 18

In hyperkalaemia with advanced CKD.

Question 19

In what two groups is hypertensive nephrosclerosis thought to be different?

Answer 19

Younger black patients (increased BP is the consequence of nephrosclerosis rather than the cause) and older Caucasian patients.

Question 20

How would you diagnose a patient with hypertensive nephrosclerosis?

Answer 20

Diagnosis of exclusion.
Hypertension should proceed proteinuria or decreased GFR by a long time frame.
Usually have left ventricular hypertrophy and hypertensive eye disease first.

Question 21

How does hypertensive nephrosclerosis compare to renal artery stenosis clinically?

Answer 21

In hypertensive nephrosclerosis:
Hypertension more acute and refractory to treatment.
Decline in GFR more rapid.
Evidence of atherosclerosis elsewhere.
Acute worsening with RAAS-blockade.

Question 22

What histological vascular changes are seen in hypertensive nephrosclerosis?

Answer 22

Fibroelastic intimal thickening with narrowing of the lumen.

Hyalinosis of afferent arteriolar walls.

Question 23

What histological glomerular changes are seen in hypertensive nephrosclerosis (secondary to ischaemia from vascular changes)?

Answer 23

Wrinkling of glomerular tuft.

Glomerulosclerosis.

Question 24

How would you manage a patient with hypertensive nephrosclerosis?

Answer 24

Manage hypertension, use ACE-inhibitors or angiotensin-receptor blockers if there is albuminuria.

Question 25

How does malignant nephrosclerosis lead to AKI?

Answer 25

Acute large increase in BP.
Damage to endothelium (haematuria).
Fibrinoid necrosis of arterioles leading to ischaemia and activation of RAAS.
AKI.

Question 26

What condition can occur secondary to malignant hypertensive nephrosclerosis?

Answer 26

Haemolytic anaemia due to shearing of blood cells.