Lecture 14- Chronic Kidney disease and cardiovascular risk Flashcards
4 main functions of the kidneys
excretory function
homeostatic function
endocrine function
metabolic function
what is CKD?
gradual loss of kidney function over time (months/years) related to disease/disorder/damage to kidneys (irreversible)
what is acute kidney injury?
sudden episode of kidney injury which occurs over hours/days (potentially reversible)
CKD defined as?
- 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
what is the measure for kidney function?
GFR
stages 1 and 2 of CKD
kidney damage with normal kidney function
stages 3 and 4 of CKD
reduced kidney function (moderate and severe)
what stage causes the most problem? higher prevalence?
stage 3
stage 5 CKD
kidney failure
implications for kidney function at age 80
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
people at risk of CKD
> 60
family history
have DM, high BP, established CVD
overweight, smoker, indigenous
2 most common causes of CKD
-diabetic nephropathy
renovascular -disease/hypertensive nephrosclerosis
3 less common causes of CKD
- reflux nephropathy- congenital problems (reflex of urine from bladder into kidney, scarring/fibrosis in kidney)
- glomerulonephritis - intrinsic kidney disease
- genetic renal disorders (PCKD)
3 tests for detection of CKD
BP
dipstick for proteinuria- early marker of kidney disease even when normal kidney function
eGFR
why is it important to do all 3 tests?
to maximise likelihood of CKD detection as there is variable overlap of indicators of kidney damage
is CKD asymptomatic?
yes- only start to feel non-specific symptoms (tired, unwell, itchy etc) when kidney function is 10-15%
how to manage aspects of CKD to slow deterioration in kidney function?
detect people earlier than symptomatic stage, can effectively intervene
-BP control, certain medication, reduce proteinuria will reduce natural progression of disease
ESKD
end stage kidney disease
generalisation about patients on dialysis in terms of cardiovascular conditions and general population
- 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
kidney and heart disease…
very intimately related
risk of ESKD related to baseline proteinuria
proteinuria= prognostic marker
- leak protein, more likely to wear kidneys out during the track
- reduce leaking, reduce wearing out
albuminuria and GFR
itself a risk factor
- albuminuria and reduced GFR predict morbidity and mortality
BP and ESKD
target BP
- salts in western diets lead to BP
- lower BP, lower kidney wearing out rate
traditional CV risk factors in kidney disease
HT, DM, lipid status, physical inactivity,
cholesterol and dialysis for general population
people with high cholesterol will do bad compared to doing good on dialysis
cholesterol and dialysis for those on dialysis
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
reverse epidemiology relevant for?
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
non-traditional CV risk factors in kidney disease
hyperphosphatemia Ca x P PTH inflammation uremic retention solutes anaemia
mechanisms of Ca/PO4 disturbance
- phosphate retention- with reduced GFR results in increased serum phosphate and suppresses vitD production
- reduced vitamin D- leads to reduced calcium absorption; this plus high serum phosphate–>low serum calcium
- PTH- stimulated by low calcium, high phosphate and low vitD
enzyme hydroxylase
produced by kidney
converts inactive vitD to active vitD
development of hyperparathyroidism
low calcium due to phosphate retention and vitD deficiency
Ca/PO4 disturbance causes
bone disease soft tissue calcification pruritus proximal myopathy premature death
when do patients develop Ca/PO4 disturbances?
in CKD stages 3-5
CKD-MBD and CVD
bone disease people more likely to have CVD
- minerals not going into bone (building up in vessel wall)
vascular calcification
- 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
two types of vascular calcification
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)
pathogenesis of vascular calcification
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
FGF-23 (fibroblast growth factor 23)
- 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
2 pathways for intestinal phosphate absorption
- 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
phosphate and CVD
poor outcomes in CVD with high rates of phosphate
organic vs inorganic phosphate and implication
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
phosphate levels in CKD
dont seem to increase until you get to CKD3
- until then, levels are normal
phosphate and CVD in general population
high normal phosphate compared to ‘normal normal’ or ‘low normal’ are at increased risk of CVD and mortality
key CKD management tasks
- lifestyle- healthy diet, exercise, no smoking, weight control
- reduce CV risk
- BP at target
- reduce proteinuria (with ACE or ARB)
- optimise calcium/phosphate
