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Cardiovascular DiseaseChronic Kidney Disease
Palestinian Cardiac Society Annual Meeting
Beitlrhem , June 28th, 2012
Riyad Said, MD, FACP, FASN
Professor of Nephrology
Jordan Hospital
Amman
Jordan
&
Chronic Kidney
Disease
Cardiovascular
disease
ESRD
Introduction
Premature Death
Chronic kidney disease is a major public health problem with adverse outcomes.
Early detection and treatment can often prevent or delay such outcomes
70- y-old Female Hypertensive Diabetic for ~ 10 years with CKD Stage lll ( e-GFR 40 ml/Min)
Cardiovascular disease( CAD )
55-Y-Old male patient Hypertensive S/P Liver Transplant 15 years ago.
ESRD on Hemodialysis for 3 months
Cardiovascular disease ( CVA )
45-Y- Old male patient Diabetic ( Type II) with ESRDOn hemodialysis for 5 Years
Calciphylaxis
40 - y – Old Male Diabetic for 8 years post LRKT for 4 years
Cardiovascular disease ( PVD )
Definition of CKD
Structural and / or Functional Abnormalities of the Kidneys for > 3 months and manifested by either:
Kidney Damage with or without decreased GFR as defined by:
Pathological Abnormalities
Markers of Kidney Damage including:
Abnormalities in the composition of Blood
Abnormalities in the Urine
Abnormalities in Imaging Tests.
GFR < than 60 ml/min 1.73 sq.m; With or Without Kidney Damage .
Calculation of e- GFR
Stages of Chronic Kidney DiseaseNKF-K/DOQI
Stage DescriptionGFR
(ml/min/1.73 m2)
1 Kidney Damage with Normal or GFR
90
2 Kidney Damage with Mild GFR
60-89
3 Moderate GFR 30-59
4 Severe GFR 15-29
5 Kidney Failure ( ESRD ) < 15 or Dialysis
Prevalence of Chronic Kidney Disease in US Population
0
10
20
30
40
50
60
70
Stage 1 Stage ll stage lll Stage lV Stage V
62.5%
32.6%
4.3% 0.2% 0.2%
KDOQI/CKD Guidelines
NKF-Dialysis Outcome Quality Initiative (NKF / DOQI)
What is ESRD?
“ The extent of renal failure which, if untreated by Dialysis or Transplantation, will result in Death of the Patient from the complications of uremia”.
GFR < 15 ml/min.
Mortality in patients starting RRT when GFR is < 7 ml is significantly higher than in those starting RRT when GFR is < 10.5ml/min.
Diabetes and Hypertension are the leading causes of End-Stage Renal Disease (ESRD)
†Incident ESRD patients; rates
adjusted for age, gender and race
1980 1984 1988 1992 1996 2000 2004 2008
No. of US patients† (in thousands)1
In patients with diabetes and hypertension, the risk of developing ESRD is 5-
6 times greater than in individuals with hypertension alone2
40% Diabetes
26% Hypertension
10% Glomerulonephritis
3% Cystic kidney
Causes of ESRD
1. USRDS 2009 Annual Data Report. NIH/NIDDKD, Bethesda, MD, 2009
2. Bakris et al. Am J Kidney Dis 2000;36:646–61
Year
ESRD is a worldwide public health problem
DIALYSIS POPULATION
Lysaght. J Am Soc Nephrol., 2002
GLOBAL MAINTENANCE TEN YEAR MEDICAL COSTS
Cardiovascular Disease
Is a complex interplay of multiple factors (Genetics, environmental, dietary….)
Is the Leading cause of death in:
The general population
Diabetics
Hypertensive
Dialysis population
Renal transplant population (after first year)
Is prevalent in patients with Early stages of renal disease
Higher prevalence with Worsening of kidney function
The 10 Leading Causes of Death in The WorldWHO 2000
0
5
10
15
20
25
30
35
Percent
Heart Disease
Cancer
Stroke
Chronic Lung Disease
Accidents
Pneumonia/Influenza
Diabetes
HIV
Suicide
Chronic Liver Disease
Seer, 2004
Lung Cancer Kidney
Failure
Colorectal
CancerBreast
Cancer
Prostate
Cancer
57
100
41
30
160
20% per year
Mortality on
Dialysis
Renal Failure Compared to Cancer Deaths in the U.S. in 2000
(in Thousands)
Cardiovascular Mortality in the General Population and in ESRD Treated by Dialysis
0.01
100
10
1
0.1
Annual mortality (%)
25–34 45–54 65–74 8535–44 55–64 75–84
Male
Female
Dialysis
General population
Age (years)
Sarnak . Am J Kidney Dis. 2000;35(suppl1):S117
Annual Cardiovascular Mortality in Patients with Chronic Renal Disease
0
2
4
6
8
10
12
14
Overall Diabetics Non-diabetics
General population
Hemodialysis
Peritoneal dialysis
Renal transplant recipients
Sarnak MJ et al J Thromb Thrombolysis 2000; 10:169-180
Foley RN et al. Am J Kidney Dis. 1998;32(suppl 3):S112-S119
15.729.5 32.3
84.067.6 61.6
0.3
2.96.1
0
20
40
60
80
100 No Events
ESRD
Death
Patients with CKD are more likelyto Die than go on Dialysis
Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31
+ DM,
- CKD
- DM,
+CKD
+ DM,
+ CKD
Medical Cohort
Pati
en
ts (
%)
“ Only the lucky CKD patients reach ESRD.”
CV Events increase at each level of Decrease GFR
0
5
10
15
20
25
30
35
40
% of Patients
CV Death Re-infarction CHF Stroke
e GFR
>75
60-74
45-59
<45
Pfeffer M Valiant Study NEJM 2004, 3
Prevalence of Cardiovascular complications
At initiation of Dialysis
Diabetic vs Non-Diabetic
38
18
24
32
4850
0
10
20
30
40
50
60
Concentric LVH Ischemic Heart
Disease
Cardiac failure
Pre
va
len
ce
(%
)
Non-Diabetic
Diabetic
Foley et al Diabetologia 1997
General
Population
Frequency Of Acute Coronary Events
Population at risk
90 60 30 15eGFR, ml/min/1.73 sq m
TransplantGrade IStructural damage
Normal function
Grade IIStructural damage
Impaired function
Grade IIIModerately
Impaired function
Grade IVSeverely imp-
aired function
Grade V
ESRD
1.67 Acute
coronary
events
/Patient Year
0.79 Acute
coronary
events
/Patient Year
0.4 Acute
coronary
events/individua
l /Year
0.004 Acute
coronary
events/individual
/Year
1 100 400 200
Causes of Death in Dialysis Patients
Coronary heart disease 9 % 6 %
Other cardiac causes 35 % 33 %
Stroke 6 % 10 %
Non-cardiovascular 50 % 51%
CHD death reduction by statins 19% per 1 mmol decrease of cholesterol*
4D study* USRDS
•Wanner, New Engl J Med (2005) 353:238
* 4D study ( Die Deutsche Diabetes Dialyse )
Diabetes and hypertension increase the risk of chronic kidney disease as well as CV disease
Risk factors: Diabetes,
hypertension, age, family history
National Kidney Foundation.
Am J Kidney Dis 2007;49(Suppl 2):S1–S180
CAD = coronary artery disease; CV = cardiovascular;
GFR = glomerular filtration rate; LVH = left ventricular hypertrophy
Initiation
Progression
End
stage
At increased risk
Heart failure
CV event
CAD, LVHAlbuminuria
Decreased GFR
Kidney failure
CVDCKD Fatal Twins
Pattern of Cardiovascular Disease in CKD Patients
Arteriosclerosis Atherosclerosis * Focal Calcific Sclerosis Arteriolosclerosis
Intima
Media Intima Media
Loss of Elasticity Critical Stenosis Dilated non-compliant
Dilated, non-compliant of Large Vessels medium sized vessels
Large vessels
Cardiac Valves
* Monckeberg’s Medial Sclerosis: ESRD, Dialysis, Aging, Diabetes Mellitus
Vascular Disease Heart Muscle
Calcification
CASHD, PVD, CVD LVH, CHF, IHD
Accelerated atherosclerosis in
prolonged maintenance hemodialysis patients has been
observed for many decades
Lindner A, Charra B, Sherrard DJ, Scribner BH
NEJM (1974) 290: 997
Cardiovascular Diseases
in Dialysis & Transplants Patients
Adapted from Dzau. Hypertension 2001;37:1047–52
Dyslipidaemia Hypertension Diabetes Smoking
Oxidative stress
Endothelial Dysfunction
Increases permeability (Microalbuminaria)
NO, local mediators, RAAS (Ang II)
Vasoconstriction Thrombosis Inflammation Plaque rupture Vascular lesion
and remodelling
Pathobiology of Progression of Vascular Diseases
45-Y- Old male patient Diabetic ( Type II) with ESRDOn hemodialysis for 5 Years
Vascular Calcification
Indicator of arterial damage.
Predictive of cardiovascular risks.
Increased LV work load.
A cause of large artery stiffness and increased pulse pressure.
Importance of vascular calcification
Bursztyn, J.Hypert (2003) 21:1953
Acceleration of Coronary Calcification at Ccr< 60 ml/min
Electron Beam Computed Tomography (Coronary Calcium Scores and CV Risk )
Patients with coronary calcium scores greater than 400 have advanced plaque disease, have
a 90% specificity for at least one obstructive coronary lesion, and are at high risk for the
development of symptomatic ischemic disease.
Rumberger JA, et al. Mayo Clin Proc. 1999;74:243-252.
Mayo Clinic EBCT Guidelines
Implication
EBCT Score Plaque Burden for CV Risk
<10 Minimal Low
11-100 Definite, Mild Moderate
101-400 Definite, Moderate High
>400 Extensive Very High
Matsuoka (2004), Clin Exp Nephrol 8: 54
Coronary Calcium Score (CACS) Predictor of Survival in HD - patients
su
rviv
al
Prevalence of left Ventricular Disorders on Starting ESRD Therapy
Newfoundland-Quebec study A cohort of 432 ESRD
Systolic
dysfunction
Patterns of Cardiac Disease
Survival in HD Patients
Survival
Time (months)
724836241200
0.2
1.0
0.8
0.6
0.4
604230186 6654
Normal
Concentric
LVH
LV dilatation
Parfrey Nephrol Dial Transplant (1996) 11: 1277
80%
50%
35%
20%
Pressure Overload ( Afterload )
(HT, Arteriosclerosis)
myocyte thickeningConcentric Hypertrophy LVH
Volume Overload ( Preload )
Hypervolemia, Anemia, A-V Fistula
myocyte lengtheningExcentric Hypertrophy LVD
Cardiomyopathy
Amplifying factorsneurohumoral activation
(sympathetic overactivity)
active vitamin D, PTH
oxydative stress
Inappropriate Ventricular Hypertrophy
Systolic DiastolicIHD CHF
Interstitial Fibrosis of The Heartin Renal Failure
normal morphology morphology of the myocardium of a patient
with chronic renal failure
Suggested pathway
ANG II
Endothelin
Both Inhance fibrosis
ACE inhibitors : reduce cardiac fibrosis
Endothelin : receptor blockers reduce cardiac fibrosis
Permissive factors : High PTH & High PhosphateAmann, Kid.Intern. (2003) 63:1296
Amann,J.Clin.Bas.Cardiol (2001)4:109
Nabokov, Kidn.Intern. (1999) 55:512
Interstitial Fibrosis of The Heart
in Renal Failure
Less Myocardial Capillaries in Uremic Patients
myocardium of a
Normotensive control patient
myocardium of a patien
with essential hypertension
myocardium of a patient
with chronic renal failure
Infarcted area (as % LV) :
30.6 ± 6.65 % vs 18.8 ± 6.58 %
→ larger infarcts
In Uremia larger Infarct Size
after Ligation of Left Coronary
Sham SNX30
40
50
60
70
80
90
infa
rcte
d a
rea
/ n
on
pe
rfu
se
da
rea
at
ris
k x
10
0
Infarcted/nonperfused area :
→ reduced penumbra
Dikow , J. Am. Soc. Nephrol. (2004) 15: 1530
Reduced ischemia tolerance
Cardiovascular Diseases in Dialysis & Transplants Patients
Chronic Kidney Disease ( CKD )
Interrelationship of CVS and CKD
Patterns of Cardiovascular Diseases
Cardiovascular Risk Factors
Prevention & Treatment
Cardiovascular Risk Factors in Dialysis Patients
All patients with CKD should be considered in the “highest risk” group for cardiovascular disease, irrespective of levels of traditional CVD risk factors.
Traditional risk factors
Non-traditional risk factors
Traditional risk factors
Proteinuria
Grade I
Transplant
CVD and CKD
Pathogenetic Factors
Grade IStructural damage
Normal function
Grade IIStructural damage
Impaired function
Grade IIIModerately
Impaired function
Grade IVSeverely imp-
aired function
Grade VESRD
Modified Traditional Factors
90 60 30 15eGFR, ml/min/1.73 sq m
Proteinuria
Natriuretic Peptides
Thrombophilia
Phosphate retention
Chronic inflammation
Angiotensin / Endothelin
Parathormone
Anemia
Leptin/NPY
The Dual Significance of Microalbuminuria
First sign of nephropathy and CKD
Proteinuria results from injury to glomerular circulation It is a Marker for Endothelial Dysfunction
Increased proteinuria is associated with progressive kidney disease.
In diabetes and hypertension, proteinuria is also an indicator of injury in the systemic circulation
Proteinuria is associated with increased CV risk.
It is Independent & Additive risk factor
Proteinuria Predicts Survival,Stroke and CHD Events in Type 2 Diabetes
Miettinen, Stroke 1996;27:2033
1
0.9
0.8
0.7
0.6
0.5
00 10 20 30 40 50 60 70 80 90 Stroke CHD
events
p<0.001
Incidence
(%)
Survival
curves
for CV
mortality
Months
A
B
C
0
10
20
30
40
A: U-Prot <150 mg/l B: U-Prot 150–300 mg/l C: U-Prot >300 mg/l
7-year follow-up of 1056 patients with type 2 diabetes in Finland
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.
Relative Importance of CV Risk Factors in Diabetes
3.2
2.3
6.5
10.0
0
2
4
6
8
10
12
Microalbuminuria Smoking Diastolic BP Cholesterol
Risk of CV MorbidityHT, DM & Microalbuminuria
1. The Hypertension in Diabetes study Group. J Hypertens
1993 ;11 :309-317.2. S F Dinneen. Arch Intern Med. 1997 ;157 :1413-1418
Risk of CV morbidity
X 4
X 2
STATE OF EMERGENCY
HYPERTENSION
+DIABETES
+Microalbuminuria
1
2
Anemia & CKD
Anemia
Cardiomyopathy
Cardiac failure
Renal failure Anemia The Critical Link
(Foley RN et al. Am J Kidney Dis 1996; 28: 53-61.)
Muirhead N et al. Am J Kidney Dis 1995; 26(2 Suppl 1): S1-S24
Pooled the Data
Mineral Metabolism, CKD, & CVD
Abnormal MM: PO4, PTH Ca, vit D Before: Vascular calcification is a passive degenerative & end-
stage process of vascular disease.
Now: Vascular calcification is an actively regulated process in
which vascular cells may acquire osteoblast like function.
Vascular calcification ( Osteocalcin, Osteopetrogin, TGF B),
Using EBCT: Patients commencing dialysis have less calcification than Hemodialysis patients.
Electron Beam Computed Tomography in the Evaluation
of Cardiac Calcification in Chronic Dialysis Patients
0
1000
2000
3000
4000
No CAD CAD No CAD CAD
Calc
ific
ation S
core
[m
edia
ns]
- 50-59- 40-49- 28-39
- 60-69
Age
Coronary Arteries
Normal renal fct.
HD patients
0
500
1000
1500
2000
2500Aortic Valve
1 year laterinitial
age: 40-49 50-59 60-69
HD patients
Braun Am J Kidney Dis (1996) 27:394
Elevated Serum PhosphorusIncreases Mortality Risk
0
0.2
0.4
0.6
0.8
1
1.2
1.4
RR
1.1-4.5 4.6-5.5 5.6-6.5 6.6-7.8 7.9-16.5
Serum Phosphorus mg/dl
Relative Mortality Risk
Relative Risk
Block et al Am J k D 1998
Serum phosphate and survival in predialysispatients with renal failure
phosphate level relative to eGFR
-- - - lowest quintile
____ middle quintiles
....... highest quintile
survival (years)
Pro
port
ion
surv
ivin
g
Kestenbaum, J.Am.Soc.Nephrol.(2005) 16:520
after adjustment, serum phosphate > 3.5 mg/dlsignificantly increased risk of death
Therapeutic options to prevent arterial calcification & stiffness
Prevent calcification: Control phosphorus to 3-5 mg/dl.
Keep CaxP < 55.
Minimize iatrogenically induced hyperphosphatemia and hypercalcemia: Minimize calcium burden (1000-1500 mg/day).
Stop active vitamin D compounds that stimulate Ca & P absorption.
Non-calcemic PO4 binders are 1st line therapy.
Vitamin D analogs are 1st line therapy.
Paricalcitol as selective VDR activator to control PTH secretion.
Renal TransplantationCardiovascular Disease&
Transplantation & the Heart
Successful renal transplantation results in:
Partial regression of LVH
Normalization of cavity size
Improved systolic function (improve cardiomyopathy)
No improvement in diastolic dysfunction
How Great is the Survival Advantage of Transplantation over Dialysis in Elderly Patients?
0
2
4
6
8
10
All 60-64 yrs > 65 yrs
Dialysis
Transplantation
Oniscu et al. Nephro Dial Transp 19: 945-5, 2004
Cardiovascular Mortality InTransplant versus Dialysis patients and in the GP
0
20
40
60
80
100
120
45-54 55-64 65-74
Age group
Deaths / 1000 P-Y
Dialysis Male
Dialysis Female
Tx Male
Tx Female
GP Male
GP Female
36
9
10
3
(EDTA 1990-1992)
Takemoto et al, Clinical Transplants, 2003
0
20
40
100
60
80
0-6 mo 6-12 mo 1-2 yr 3-5 yr >5 yr
Acute rejection
Chronic allograft
nephropathy
Death with
functioning
graft
Other
Causes of Kidney Graft Loss (UNOS 1987-2001)
Causes of death with a functioning graft after renal transplantation (1st 5 years)
67.874 first renal transplants, 1994–2000
CVD
39.6%
Others
27.2%
Tumours
9.3%
Infections
24.0%
USRDS = United States Renal Data System
Cardiovascular Risk Factors in Renal Transplant Recipients
Risk Factors shared with General Population
Risk Factors shared with other Renal Patients
Proteinuria, Low GFR
Anemia
Abnormal mineral metabolism
Risk Factors specific to Renal Transplant Patients
Acute Rejection
Chronic Rejection
Immunosuppressants
Viral infections Herpes virus, CMV ?
Serum Creatinine levels at 1-year post-Tx are associated with CV death
CV
death
-fre
e s
urv
ival
(%)
Meier-Kriesche H-U, et al. Transplantation 2003;75:1291–6
Time post-transplant (months)
2.6–4.0
2.2–2.5
1.9–2.1
1.7–1.8
1.5–1.6
1.3–1.4
< 1.3
SCr
(mg/dl)
0 12 36 7260 120
100
98
96
94
92
90
Risk Factors of Ischemic Heart Disease after Renal Transplantation
Traditional risk factors
140–159 or 90–99 5.2–6.1
0
0.5
1
1.5
2
2.5
3
Rela
tive R
isk
Diabetes Blood Pressure Cholesterol
ControlTransplant
Kasiske et al. J Am Soc Nephrol. 2000: 11:1735-1743.
Lipid Abnormalities
PERCENT GP CKD With NS
CRI DIALYSIS
Transplant
Total cholesterol >240 mg/dL
20 60-90 25 60 *
LDL cholesterol >130 mg/dL
40 85 30 60 *
HDL cholesterol <35 mg/dL
15 50 50 15
Triglycerides
>200 mg/dL
15 60 50 30
LP (a) > 30 15 60 30 25
HyperlipidemiaAssociated With Immunosuppressive Regimens
Combination Hyperlipidemia
Azathioprine + prednisone +
Azathioprine + prednisone + cyclosporine +++
MMF + prednisone + cyclosporine +++
Azathioprine + prednisone + tacrolimus ++
MMF + prednisone + tacrolimus +
Sirolimus + prednisone + cyclosporine ++++
Sirolimus + prednisone + tacrolimus +++
MMF + prednisone + sirolimus +++
MMF = mycophenolate mofetil, + = least association, ++++ = greatest association.
Fluvastatin in RT RecipientsALERT Trial
2102 Renal Transplant
Fluvastatin versus Placebo 6 years
LDL-Cholesterol decreased by 32 %
Major Adverse CV events decreased by 17 %
Risk of Cardiac Death decreased by 38 %
Definite non-fatal MI risk decreased by 32 %
Incidence of PTDMmultivariate analysis study
Cosio FG, et al. Kidney Int. 2001;59:732-737.
Factors Associated with Increased Risk for Developing New-onset Diabetes after Transplantation
Increased risk for developing
New-onset diabetes after transplantation
Black orhispanic ethnicity
Family historyof diabetes
Age > 40 years
Cadaver kidney
Immunosuppressive
therapy
Obesity
Glucose intolerance
Hepatitis CVirus
infectionMetabolic syndrome:• High TG• Low HDL• Hypertension• Hyperuricemia
Consequences of development of new-onset diabetes after transplantation
Development of new-onsetdiabetes after transplantation
Graft functionand survival
Patientsurvival
Risk for CVD
Proposed mechanisms:• Diabetic nephropathy.• Hypertension.• Low immunosuppressant doses
Proposed mechanisms:• Increased incidence of infection.• Increased risk of sepsis.• CVD.
Proposed mechanisms:• Hyperinsulinemia.• Glucose intolerance.• Insulin resistance.• Dyslipidemia.• Hypertension.
Macro. & Microvascular complications
In Transplant Diabetes is a KILLER Disease!
+ 63% (p<0.0001)
At 3 years New Onset Diabetes after Transplant Increase Graft Failure
+ 87% (p<0.0001)
At 3 years New Onset Diabetes after Transplant Increase Patient Death
Kasiske B et al. USRDS.11,659 Patients
Kasiske B et al..Diabetes Mellitus after Kidney Transplantation in US. AJT 2003;3: 178-185
Post-transplant Hypertension
Diseased native kidneys
Chronic rejection
Steroids
Cyclosporine
Tacrolimus
Renal artery stenosis
Transplant glomerulonephritis
Hypercalcemia
29,751 Cadaveric renal Tx recipients at one yearOplez et al, Kid. Int 1998
Hypertension is found in almost 90% of renal graft recipients
Immunosuppressive DrugsCardiovascular Risk Profile
Drug BP Lipids Wt Diabetes Anaemia
PRD ++ +++ +++ +++ -
CsA +++ ++ ± + -
TAC +++ ++ ± +++ -
RAP - +++ ± - +
MPA - - ± - +
CD25 MAb - - - - -
Cardiovascular Diseases in Dialysis & Transplants Patients
Chronic Kidney Disease ( CKD )
Interrelationship of CVS and CKD
Patterns of Cardiovascular Diseases
Cardiovascular Risk Factors Traditional
Non - Traditional Risk Factors Common for Renal Patients.
Risk Factors Specific to Renal Transplants.
Prevention & Treatment
Strategies for reducing cardiovascular complications in CKD Patients
Measures proven by intervention trials: Life-style modification:
Exercise, weight reduction, smoking & Alcohol.
Disease modification:
Hypertension, hyperlipidaemia, diabetes mellitus, anaemia & hyperphosphatemia.
Modification of Immunosuppresives:
• Corticosteroid withdrawal/dose reduction.
• RAP dose reduction or elimination/avoidance.
Therapies suggested by epidemiologic analysis: Endothelial disorders: Antiplatlet therapy.
Other therapies: EPO, aspirin, folate, vitamin E ? & vitamin C ?
Emerging Goals in Transplantation
Reduce Side Effects
of
Immunosuppression
Preservation of
Renal Function
Decrease Risk of
Cardiovascular
Disease
Tailoring Immunosuppression
Risk Factor or Agents to reduce complication or withdraw
Severe hyperlipidemia Cyclosp, Pred, Sirolimus
Severe hypertension Cyclosp, Pred
DM difficult to control Pred, Tacrol
New DM Post-transplant Pred, Tacrol, Cyclosp
Very low renal function Cyclosp, Tacrol
Conclusion 1
All patients with CKD should be considered in the “highest risk” group for cardiovascular disease, irrespective of levels of traditional CVD risk factors.
Conclusion 2
Cardiovascular disease after renal transplantation often is the expression of disease process that first started with onset of renal dysfunction many years before.
It is related to a high prevalence and accumulation of risk factors before and after transplantation
Hypertension, diabetes and hyperlipidemia are well-recognized risk factors and are strongly linked to the immunosuppressive therapy
Reducing cardiovascular risk can only be accomplished by aggressively reducing the impact of these defined risk factors early after the onset of chronic kidney disease and effectively after renal transplantation
Unlikely that one golden bullet will eliminate all excess cardiac mortality in the renal patient
Cardiovascular
ProtectionRenoprotection
Conclusion 3