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