CKD

Question 1

Define CKD.

Answer 1

Proteinuria or haematuria ± a reduction in GFR to <60mL/minute/1.73 m^2 for ≥3 months

Question 2

What are the potential causes of CKD?

Answer 2

1. Diabetes mellitus
2. Hypertension
3. Polycystic kidney disease
4. Obstructive uropathy
5. Glomerular nephrotic and nephritis syndromes

Question 3

Describe the mechanisms involved in the pathophysiology of CKD.

Answer 3

1. Raised intra-glomerular pressure:
   - nephrons scar and ‘drop out’
   - increase in blood flow per nephron and hyperfiltration in an attempt to normalise GFR
   - may result in proteinuria
2. Glomerular damage:
   - raised intra-glomerular pressure = increased wall stress and endothelial injury
   - increased strain on mesangial cells = increased matrix deposition mediated by angiotensin II and cytokine release
   - proteinuria/factors bound to albumin may lead to:
   (i) direct proximal tubular cell injury + local cytokine synthesis
   (ii) interstitial scarring
   (iii) myofibroblast activation (further fuelling fibrogenic process)
3. Tubulointerstitial scarring:
   - proteinuria may be harmful to the tubulointerstitium

Question 4

Describe the different stages of CKD (1-5).

Answer 4

Stage 1:

• GFR >90
• must have evidence of kidney damage

Stage 2:

• GFR 60-89
• must have evidence of kidney damage

Stage 3A:

• GFR 45-59
• ± evidence of kidney damage

Stage 3B:

• GFR 30-44
• ± evidence of kidney damage

Stage 4:
- GFR 15-29

Stage 5:
- GFR <15 (ESRD)

Question 5

What evidence of kidney damage is required to diagnose someone with Stage 1 or 2 CKD?

Answer 5

• urinary abnormalities (proteinuria, haematuria)
• structural abnormalities (abnormal renal imaging)
• genetic disease (autosomal dominant polycystic kidney disease)
• histologically established disease

Question 6

What are the complications of CKD?

Answer 6

1. anaemia
   - due to deficiency of EPO as GFR declines
   - typically normochromic and normocytic
2. renal osteodystrophy:
   - may be due to an elevation in PTH as a result of phosphorus retention and hyocalcaemia from 1,25 vitamin D deficiency as the GFR declines
3. hypertension:
   - reduced renal blood flow causes RAAS stimulation leading to Na+ and H2O retention
   - Angiotenin II increases cardia pre-load and after-load and raises myocardial demand
   - chronic sympathetic nervous system activation reduces adrenoreceptor sensitivity, increases LVH and increases myocyte apoptosis
4. acid base imbalance:
   - metabolic acidosis is common due to the inability of the kidney to excrete acid once the estimated GFR is <50 mL/minute
   - anion gap is typically normal, but may be increases in uraemia
5. uraemia

Question 7

Describe the role of ACE-Is and ARBs in CKD.

Answer 7

1. ACE-Is:
   - inhibitors of ACE are often reduce the formation of the more potent angiotensin II
   - lower arteriolar resistance and increase venous capacity
   - decrease cardiac output, cardiac index, stroke work and volume
   - lower resistance in blood vessel in the kidneys
   - can lead to increased natriuresis
2. ARBs:
   - act at the sites of angiotensin receptors
   - used to prevent angiotensin II from acting on its receptors
   - causes vasodilation, reduced secretion of vasopressin, and reduced production and secretion of aldosterone
   - combined effect reduced BP

Question 8

Give examples of ACE-Is.

Answer 8

Captopril + ramipril

Question 9

Give examples of ARBs.

Answer 9

Losartan + Valsartan