Lecture 14- Chronic Kidney disease and cardiovascular risk

Question 1

4 main functions of the kidneys

Answer 1

excretory function
homeostatic function
endocrine function
metabolic function

Question 2

what is CKD?

Answer 2

gradual loss of kidney function over time (months/years) related to disease/disorder/damage to kidneys (irreversible)

Question 3

what is acute kidney injury?

Answer 3

sudden episode of kidney injury which occurs over hours/days (potentially reversible)

Question 4

CKD defined as?

Answer 4

• lost more than half of kidney function (GFR) with or w/o evidence of kidney damage OR
• normal/abnormal GFR but have evidence of kidney damage e.g. proteinuria

Question 5

what is the measure for kidney function?

Answer 5

GFR

Question 6

stages 1 and 2 of CKD

Answer 6

kidney damage with normal kidney function

Question 7

stages 3 and 4 of CKD

Answer 7

reduced kidney function (moderate and severe)

Question 8

what stage causes the most problem? higher prevalence?

Answer 8

stage 3

Question 9

stage 5 CKD

Answer 9

kidney failure

Question 10

implications for kidney function at age 80

Answer 10

CKD is a disease of ageing

• therefore kidney function usually declines as you get older
• if no other factors for kidney damage present, then not CKD

Question 11

people at risk of CKD

Answer 11

> 60
family history
have DM, high BP, established CVD
overweight, smoker, indigenous

Question 12

2 most common causes of CKD

Answer 12

-diabetic nephropathy

renovascular -disease/hypertensive nephrosclerosis

Question 13

3 less common causes of CKD

Answer 13

• reflux nephropathy- congenital problems (reflex of urine from bladder into kidney, scarring/fibrosis in kidney)
• glomerulonephritis - intrinsic kidney disease
• genetic renal disorders (PCKD)

Question 14

3 tests for detection of CKD

Answer 14

BP
dipstick for proteinuria- early marker of kidney disease even when normal kidney function
eGFR

Question 15

why is it important to do all 3 tests?

Answer 15

to maximise likelihood of CKD detection as there is variable overlap of indicators of kidney damage

Question 16

is CKD asymptomatic?

Answer 16

yes- only start to feel non-specific symptoms (tired, unwell, itchy etc) when kidney function is 10-15%

Question 17

how to manage aspects of CKD to slow deterioration in kidney function?

Answer 17

detect people earlier than symptomatic stage, can effectively intervene
-BP control, certain medication, reduce proteinuria will reduce natural progression of disease

Question 18

ESKD

Answer 18

end stage kidney disease

Question 19

generalisation about patients on dialysis in terms of cardiovascular conditions and general population

Answer 19

• earlier age on dialysis, risk of dying from cardiovascular condition is same as someone in their 70s/80s
• dialysis patients- 200-300x increase of CVD compared to general population
• 50% of people on dialysis will die from CVD
• vast majority of people in stage 3 CKD on dialysis die along the way from CVD- which is why they dont progress to next stages
• patients with CKD are 20 times more likely to die from CV event than survive to reach dialysis

Question 20

kidney and heart disease…

Answer 20

very intimately related

Question 21

risk of ESKD related to baseline proteinuria

Answer 21

proteinuria= prognostic marker

• leak protein, more likely to wear kidneys out during the track
• reduce leaking, reduce wearing out

Question 22

albuminuria and GFR

Answer 22

itself a risk factor

- albuminuria and reduced GFR predict morbidity and mortality

Question 23

BP and ESKD

Answer 23

target BP

• salts in western diets lead to BP
• lower BP, lower kidney wearing out rate

Question 24

traditional CV risk factors in kidney disease

Answer 24

HT, DM, lipid status, physical inactivity,

Question 25

cholesterol and dialysis for general population

Answer 25

people with high cholesterol will do bad compared to doing good on dialysis

Question 26

cholesterol and dialysis for those on dialysis

Answer 26

do better with high cholesterol (Eat better, dialysis needs more protein intake)

• low cholesterol- malnutrition
• tried to use statins to reduce cholesterol, makes no difference

Question 27

reverse epidemiology relevant for?

Answer 27

cholesterol, obesity, hypertension
e.g. overweight people and higher BP people do better on dialysis
= confounding factors
- therefore traditional CVD risk factors not the whole answer for why people have burden of CVD in kidney disease

Question 28

non-traditional CV risk factors in kidney disease

Answer 28

hyperphosphatemia
Ca x P
PTH
inflammation
uremic retention solutes 
anaemia

Question 29

mechanisms of Ca/PO4 disturbance

Answer 29

1. phosphate retention- with reduced GFR results in increased serum phosphate and suppresses vitD production
2. reduced vitamin D- leads to reduced calcium absorption; this plus high serum phosphate–>low serum calcium
3. PTH- stimulated by low calcium, high phosphate and low vitD

Question 30

enzyme hydroxylase

Answer 30

produced by kidney

converts inactive vitD to active vitD

Question 31

development of hyperparathyroidism

Answer 31

low calcium due to phosphate retention and vitD deficiency

Question 32

Ca/PO4 disturbance causes

Answer 32

bone disease
soft tissue calcification
pruritus 
proximal myopathy
premature death

Question 33

when do patients develop Ca/PO4 disturbances?

Answer 33

in CKD stages 3-5

Question 34

CKD-MBD and CVD

Answer 34

bone disease people more likely to have CVD

- minerals not going into bone (building up in vessel wall)

Question 35

vascular calcification

Answer 35

• clinical consequence of hyperphosphatemia in CKD
  build up of calcium form bone in blood vessels–>makes it stiff
• blood vessels in endothelial layer disrupts function of kidney–>contributing to arterial stiffness

Question 36

two types of vascular calcification

Answer 36

intimal- measure of atherosclerotic load within intimal layer
medial- stiffness- more related to bone and mineral abnormalities
-doesnt lead to occlusive atherosclerotic problems
- have increased arteriosclerosis (vascular stiffness–>LVH–>sudden death)

Question 37

pathogenesis of vascular calcification

Answer 37

active process
we have promoters and inhibitors of vascular calcification
- normally so many inhibitors that we dont calcify
- on dialysis and kidney disease- more promoters- therefore pro calcific state

Question 38

FGF-23 (fibroblast growth factor 23)

Answer 38

• phosphotonin, produced by bone
• maintains phosphate homeostasis, binds to FGF receptor
• acts on vitD to reduce its levels (people become vitD deficient, low levels of phosphate absorption as well)
• kidney disease- have greater levels of FGF-23, even more in dialysis
• higher levels- increase mortality

Question 39

2 pathways for intestinal phosphate absorption

Answer 39

• paracellular pathway- passive diffusion down an electrochemical potential gradient (important following a meal, when intraluminal conc is high)
• transcellular Na dependent carrier-mediated pathway- under control of active vitD and other regulatory signals

Question 40

phosphate and CVD

Answer 40

poor outcomes in CVD with high rates of phosphate

Question 41

organic vs inorganic phosphate and implication

Answer 41

organic- incompletely hydrolysed and absorbed (phytin, casein)
inorganic- readily hydrolysed and absorbed (food additives)
implication- phosphate burden from food additives disproportionately high relative to their dietary content and relative to protein-based phosphate

Question 42

phosphate levels in CKD

Answer 42

dont seem to increase until you get to CKD3

- until then, levels are normal

Question 43

phosphate and CVD in general population

Answer 43

high normal phosphate compared to ‘normal normal’ or ‘low normal’ are at increased risk of CVD and mortality

Question 44

key CKD management tasks

Answer 44

• lifestyle- healthy diet, exercise, no smoking, weight control
• reduce CV risk
• BP at target
• reduce proteinuria (with ACE or ARB)
• optimise calcium/phosphate