Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent

8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent

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CHRONIC KIDNEY DISEASE: AS ACARDIOVASCULAR RISK

EQUIVALENT

AN OVERVIEW

Prof A AkinsolaOAU Ile Ife


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MAGNITUDE OF CKDStage Description GFR

ml/min/1.73m2US prevalence,

1000sUS prevalence

1 Kidney damagewith normal orincreased GFR

? 90 5900 3.3

2 Kidney damagewith mildlydecreased GFR

60 89 5300 3.0

3 Moderatelydecreased GFR

30 59 7600 4.3

4 Severelydecreased GFR

15 29 400 0.2

5 Kidney failure < 15 or dialysis 300 0.1

Australia 18% had one indicator of CKD

Nigeria: only hospital data late stages of CKD

:28% medical admission,300 400/million


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CV Mortality in CKD Vs General Population

Cardiovascular burden of CKD is enormous:


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Approximate Prevalence of CVD in the

General Population and CKDIschemic Heart

Disease (Clinical)

LVH

( Echo)

Heart failure (Clinical)

General Population 813 (Age 55-64) 20 36

CKD stages 3-4

(diabetic and

nondiabetic kidney

disease)

NA 25-50 (varies with

level of kidney

functions)

NA

CKD stage 1-4

(kidney transplant

recipients)

15 50-70 NA

CKD stage 5

(heamodialysis)

40 75 40

CKD stage 5

(peritoneal dialysis)

40 75 40


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THE BURDEN OF CARDIOVASCULAR (CV)

EVENTS IN CKD ALSO ENORMOUS

Primary cause of morbidity/prematuremortality in CKD patients

Only 16% of CKD patients have normal ECGat first dialysis

Majority have LVH, Systolic dysfunction/LVdialtation

50% of deaths have a CV cause Dialysis population have a 10-20 fold higher

risk than the general population for CVmortality


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Risk for cardiac mortality in patients


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SPECTRUM OF CVS DISEASE IN CKD

MYOCARDIAL

Pathophysiology: Pressure/volume overload due toHT, Anaemia, Hyperdynaemic circulation, PTH,elevated SNS activity, inflammation

Structural alterations

Ventricular remodelling LVH

LVH (concentric (Pr); Eccentric (volume overload)

HF (occuring in 30-50%, [CKD stages 3 & 4]


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Spectrum of CV Disease in CKD


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BLOOD V V:

Pathophysiology:

Heamodynamic/metabolic changes

(A) Arterial remodelling collagen,calcification, extracellular matrix,

arteriosclerosis arterial stiffening(B) Intimal arteriosclerotic plaque formation

coronary artery disease

1 HD* (finding of CAD in >50% of CKD stage 5

by coronary angio


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PROPOSITIONS Increased prevalence of

traditional/non traditionalCV rf in CKD

CKD itself, is an

independent risk equivalent

CV rf are also risk factorsfor progression of CKD

Presence of Cardiovascular

Disease is also a risk factorfor CKD


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Proposition 2:

The 2 major marlers of CKD ie

Microalbuminuria -

GFR < 60 ml/mn -

are both independent risk factors for CV disease

Reduced GFR: Increased levels of non-traditional risk

factors

May mirror severity of vascular disease

May be a measure of residual confoundingtraditional risk factors

May compromise optimal treatment(aspirin, b-blockers, ACET)


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Microalbuminuria:

A maker of generalised endothelialdysfunction and vascular permeability

May be associated with other risk factors

or surrogates Predictor for early or incipient renal failure


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Proposition 2:

Cardiovascular Risk Factors are

prevalent in CKD

Traditional: specified by Framingham Heart studypatient ( see table) Table

Non-traditional: uraemia related increases in

prevalence with declining GFR RF for LVH

older age, Higher Systolic BP, Lower Hb and

decreased GRF

RF for atherosclerosis:DM, Higher total cholesterol, lower high density, LPcholesterol, smoking, higher systolic BP


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Others:

Inflammation:

An integral part in the pathogenesis ofatherosclerosis.

Markers: C- reactive problem (CRP)independent predictor of all cause

mortality and CV disease, mortality [MDRDstudy]

Rates CRF > 2.2mg/l increases as GFRCRR (1L-6, TNF reception I & II are assoctiated

with increased odds for coronary events[nurseshealth study]


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OXIDATIVE STRESS

A common pathway for inflammation, insulinresistance etc. in the pathogenesis of

atherosclerosis Evidence from studies: Antioxidants in

secondary prevention of cardiovasculardisease in CKD [SPACE]


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METABOLIC SYNDRONME abdominal fat

accumulation, HT, triglyceride, HDL

Glucose

Major components of metabolic syndrome

hyperinsulinaemia and insulin resistance arepresent in CKD and this is associated withincreased CV disease risk.


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HYPERHOMOCYSTEINAEMIA + OTHER

THIOLS

HC- is associated with CV disease risk in thegeneral population; similarly so in kidney

failure Studies lacking for early CKD

Lowering with Acetyl cystein, folic acid/Vit B6,12 may be beneficial


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Endothelial cell dysfunction and

injury

Abnormal endothelium- dependent

vasodilation - is a predictor of CV diseaseevents and mortality in kidney failure, it isindependent of arterial stiffness in LVH


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RISK FACTORS FOR ARTERIOSCLEROSIS

Impaired endothelium dependentvasodilatation contributes to arterialstructural alterations in patients with CKD

Abnormal Ca and PO4 metabolism:

Increased risk of mortality and 20 PTH in Dxoccurs when >6.5mg/dl PO4 AND Ca++ x

PO product > 72mg2

/dl2

.Recommendation PO4 2.5-6.5mg/dl; Cax PO4 < 72mg2/dl2.


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Mortality from hyperphosphataemia


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Leads to large vessel calcification:

(i) arterial stiffening (ii) increased pulse

pressure (iii) decreased coronary perfusion(iv) LVH

2 Types of calcificationIntimal develop in 80-90% of

atherosclerotic plaques that protrude intovessel

lumen ischaemia and necrosis


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Media calcification (Monckenberg sclerosis)occurs diffusely in the tunica media (common in CKD and diabetics)

vascular rigidity, decreases compliance

systolic hypertension + increase pulse,wave velocity, contributes to LVH andcompromised diastolic coronary flow.

? deficit of a glycoprotein fetuin apotent inhibitor of calcification in CKD??


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ANAEMIA: as a cardiovascular risk

factor

Prevalence of anaemia = 25% in pts withCrCl > 50ml/min;

with CrCl (35 49ml/min = 44%

(25 34ml/min = 51%

(< 25ml/min = 44%

A decline in Hb starts at a GFR 70min/min,

in males and 50ml/min in females


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Physiological alterations:

CO, cardiomegaly, LVH, CHF

A close relationship between LVH andaneamia

EPO treatment has led to partial regression

Correction of aneamia improves survival


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DYSLIPIDAEMIA:

NHNES data have linked the metabolicsyndrome and dyslipidaemia to developmentof CKD

Endothelial dysfunction and atherosclerosis ofthe renal vasculature possibly a majorcomponent of both diabetic and non-DM CKD


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Smoking an independent risk factor for bothCVD and CKD

ces CV disease death rates in CKD

Nicotin + components of tar upregulationof adhesion molecules

Promotes oxidation and entry of LDL

cholesterol into the vascular sub-endothelium


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Increased Sympathetic N.S activity:

Renal Ischaemia, Ang.II, cerebral NO

contribute to stimulation of symp. Activity Renal and Cardiac injury form SNS activity

may be enhanced by NO and oxidativestress


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Conclusion:CKD, even in the early stage

constitutes a major CV risk

equivalent and thus poses a

great challenge perhaps greater

than that of RRT.


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Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent