Cardiovascular Complications Of

Chronic Kidney Disease

Dr Atir Khan
Consultant Physician Diabetes & Endocrinology
West Wales Hospital, Carmarthen

Markers of kidney dysfunction

Raised Albumin / Creatinine ratio
Proteinuria.
Abnormalities in urine sediments (RBC
casts).
Abnormal findings on imaging (U/S scan
etc.).
GFR overall best measure of kidney
damage.
Kidney dysfunction can be diagnosed
without knowledge of the cause

Stages of CKD
STAGE GFR

Action

90 ( GFR)

Dx. + Rx. of comorb

slow progression
CVD risk reduction

60 89

Estimating progression

30 59

Evaluate & Rx. Compli.

15 29

Prepare for kid. Replac

< 15 (or dialysis)

Kidney replacement

CVD in CKD: Epidemiology 1

40 50% of all deaths in CKD are due to
CVD.
Deaths from CVD are 20 times more in CKD
than general population.
Increase in prevalence of M.I.
Increase in rate of fatal M.I.

CVD in CKD: Epidemiology 2

Some facts:
75% patients on Dialysis have evidence of Left
ventricular hypertrophy.
30% patients before reaching ESRD will have
IHD.
Patients with decreased GFR are more likely
to die of CVD than ESRD.

Atherosclerosis (AS) and CKD

Some facts
AS is accelerated in CKD
AS is more frequent in CKD
AS is more prevalent in CKD
Atheroma size is bigger
Vessel wall is thickened in CKD

Atherosclerosis and CKD 2

Some facts
Morphology of coronary plaque is different in
uremic and non-uremic patients.
Stays plaque classification I VII
Uremic patients usually have type VII
plaques (i.e. with calcification & AS).
AS is more advanced in CKD.

Risk factors for CVD in CKD

Hypertension
Diabetes
Hyperlipidemia
Smoking

Uremia specific CVD risk factors

Anemia
Hyperphosphatemia.
Chronic inflammation.
Oxidative stress.
Albuminuria.
Thrombogenic risk factors.

Uremia specific CVD risk factors

Anemia
Hyperphosphatemia.
Chronic inflammation.
Oxidative stress.
Albuminuria.
Thrombogenic risk factors.

Chronic inflammation in CKD 1

CRP is produced from hepatocytes in
response to cytokines IL-1 & IL-6.
CRP is raised in CKD.
Raised CRP has been found to be predictor of
all cause and CVD mortality in CKD.
It is not clear if CRP is raised due to Chronic
Inflammation or it is a cause of AS and
endothelial dysfunction.

Chronic inflammation in CKD 2

IL-6 is produced by TLymph., monocytes,
dendritic cells, adipocytes & fibroblasts.
It is a pro-inflmmatory cytokine.
IL-6 production is induced by TNF-, IL1-,
bacterial LPS & oxidative stress.
Raised IL-6 levels have been have been seen
in CKD.
Raised IL-6 in dialysis patients predicts AS,
CV and all cause mortality.

Chronic inflammation in CKD 3

TNF-, another pro-inflammatory cytokine.
It affects lipid metabolism, endothelial
dysfunction, insulin secretion, activation of
immune cells.
CKD is associated with raised TNF-.
Creates insulin insensitivity.
Up regulates renin-angiotensin system.

Uremia specific CVD risk factors

Anemia
Hyperphosphatemia.
Chronic inflammation.
Oxidative stress.
Albuminuria.
Thrombogenic risk factors.

Oxidative stress and CKD

Accumulation of highly reactive oxygen
radicals.
Oxygen superoxide, Hydro-oxyradicals,
hydroxyperoxide.
These radicals not necessarily pathogenic per
se. .
but these act as physiologic signal
molecules for Angiotensin II, which is
proinflammatory.

CKD and Heart

LV measurement (LVH/LVF) is an early
abnormality.
It affects 39 74% pre-dialysis patients.
..and 82% on maintenance dialysis.
LVH predicts mortality in CKD.
LV systolic & diastolic dysfunction
contributes to mortality in CKD.

Predictors of LVH in CKD

Anemia.
Raised PTH.
Increased sympathetic tone.
Hypertension.

CVD risks in CKDINDEPENDENT OF A.S.

Anemia and CVD in CKD
Decreased Hb results in decreased Oxygen
delivery & increased sympathetic activity.
Increased heart rate.
Increased cardiac output leading to LVF.

Controversy: correction of anemia does not

result in decrease in CVD events.

CVD risks in CKDINDEPENDENT OF A.S.

CKD patients show increased sympathetic
tone.
During dialysis, catecholamines levels
comparable to phaeochromocytoma have
been found.
2ndry hyperparathyroidism, driven by Ca and
Po4 abnormalities contributes to CVD risk.

Conclusion
Deaths from CVD in CKD are 20-times high.
In CKD the CVD occurs very early.
A.S. is the main underlying problem.
CKD is a pro-inflammatory state leading to AS.
CVD risk factors are common in CKD.
CKD specific CVD risk factors complicate the
problems further in CKD.
CVD events in CKD are more prevalent, more
frequent and more fatal.
Early detection, treatment of risk factors and
delay the progression of CKD is needed.

Conclusion 2
Systolic and diastolic dysnfunction is
common and contributes to CVD mortality.
Increased prevalence of LVH.
Increased prevalence of PVD
Increased prevalence of CVA

Thank You