Cardiovascular Complications Of Chronic Kidney Disease. Dr Atir Khan Consultant Physician Diabetes & Endocrinology West Wales Hospital, Carmarthen

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1 Cardiovascular Complications Of Chronic Kidney Disease Dr Atir Khan Consultant Physician Diabetes & Endocrinology West Wales Hospital, Carmarthen

2 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

3 Stages of CKD STAGE GFR Action 1 90 ( GFR) Dx. + Rx. of comorb slow progression CVD risk reduction Estimating progression Evaluate & Rx. Compli Prepare for kid. Replac 5 < 15 (or dialysis) Kidney replacement

4 CVD in CKD: Epidemiology % 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.

5 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.

6 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

7 Atherosclerosis and CKD 2 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.

8 Risk factors for CVD in CKD Hypertension Diabetes Hyperlipidemia Smoking

9 Uremia specific CVD risk factors Anemia Hyperphosphatemia. Chronic inflammation. Oxidative stress. Albuminuria. Thrombogenic risk factors.

10 Uremia specific CVD risk factors Anemia Hyperphosphatemia. Chronic inflammation. Oxidative stress. Albuminuria. Thrombogenic risk factors.

11 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.

12 Chronic inflammation in CKD 2 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.

13 Chronic inflammation in CKD 3 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.

14 Uremia specific CVD risk factors Anemia Hyperphosphatemia. Chronic inflammation. Oxidative stress. Albuminuria. Thrombogenic risk factors.

15 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.

16 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.

17 Predictors of LVH in CKD Anemia. Raised PTH. Increased sympathetic tone. Hypertension.

18 CVD risks in CKD INDEPENDENT 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.

19 CVD risks in CKD INDEPENDENT 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.

20 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.

21 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

22 Thank You