cardiovascular complications of chronic kidney disease complic… · chronic inflammation in ckd...

Cardiovascular Complications Of Chronic Kidney Disease

Dr Atir KhanConsultant 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 CKDSTAGE GFR Action

1 ≥ 90 ( GFR) Dx. + Rx. of comorbslow progressionCVD risk reduction

2 60 – 89 Estimating progression

3 30 – 59 Evaluate & Rx. Compli.

4 15 – 29 Prepare for kid. Replac

5 < 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.

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.

CVD in CKD: Epidemiology – 2

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 (AS) and CKD

Some facts

• Morphology of coronary plaque is different in uremic and non-uremic patients.

• Stay’s plaque classification I – VII

• Uremic patients usually have type VII plaques (i.e. with calcification & AS).

• AS is more advanced in CKD.

Atherosclerosis and CKD – 2

• Hypertension

• Diabetes

• Hyperlipidemia

• Smoking

Risk factors for CVD in CKD

• 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.

Uremia specific CVD 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.

• IL-6 is produced by T–Lymph., monocytes, dendritic cells, adipocytes & fibroblasts.

• It is a pro-inflmmatory cytokine.

• IL-6 production is induced by TNF-α, IL1-β, 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 – 2

• TNF-α, another pro-inflammatory cytokine.

• It affects lipid metabolism, endothelial dysfunction, insulin secretion, activation of immune cells.

• CKD is associated with raised TNF-α.

• Creates insulin insensitivity.

• Up regulates renin-angiotensin system.

Chronic inflammation in CKD – 3

• Anemia

• Hyperphosphatemia.

• Chronic inflammation.

• Oxidative stress.

• Albuminuria.

• Thrombogenic risk factors.

Uremia specific CVD risk factors

• 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.

Oxidative stress and CKD

• 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.

CKD and Heart

• Anemia.

• Raised PTH.

• Increased sympathetic tone.

• Hypertension.

Predictors of LVH in CKD

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 CKD…INDEPENDENT OF A.S.

• CKD patients show increased sympathetictone.

• During dialysis, catecholamines levels comparable to phaeochromocytoma have been found.

• 2ndry hyperparathyroidism, driven by Ca and Po4 abnormalities contributes to CVD risk.

CVD risks in CKD…INDEPENDENT OF A.S.

• 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

• Systolic and diastolic dysnfunction is common and contributes to CVD mortality.

• Increased prevalence of LVH.

• Increased prevalence of PVD

• Increased prevalence of CVA

Conclusion – 2

Thank You