8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
1/32
CHRONIC KIDNEY DISEASE: AS ACARDIOVASCULAR RISK
EQUIVALENT
AN OVERVIEW
Prof A AkinsolaOAU Ile Ife
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
2/32
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
3/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
4/32
CV Mortality in CKD Vs General Population
Cardiovascular burden of CKD is enormous:
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
5/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
6/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
7/32
Risk for cardiac mortality in patients
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
8/32
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]
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
9/32
Spectrum of CV Disease in CKD
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
10/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
11/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
12/32
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)
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
13/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
14/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
15/32
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]
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
16/32
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
17/32
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]
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
18/32
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.
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
19/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
20/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
21/32
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.
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
22/32
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
23/32
Mortality from hyperphosphataemia
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
24/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
25/32
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??
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
26/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
27/32
Physiological alterations:
CO, cardiomegaly, LVH, CHF
A close relationship between LVH andaneamia
EPO treatment has led to partial regression
Correction of aneamia improves survival
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
28/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
29/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
30/32
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
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
31/32
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.
8/13/2019 Akinsola Chronic Kidney Dis Ease as a Cardiovascular Risk Equivalent
32/32