Cardiovascular Disease Cardiovascular Disease in Dialysis and Renal in Dialysis and Renal

TransplantationTransplantation

Jeffrey Guardino, MD FACCJeffrey Guardino, MD FACCStanford HospitalStanford Hospital

Division of CardiologyDivision of Cardiology

Magnitude of CVD RiskMagnitude of CVD Risk

CKD has reached epidemic proportions CKD has reached epidemic proportions with ~650,000 patients requiring dialysiswith ~650,000 patients requiring dialysis

Prevalence of CAD in CKD patients is Prevalence of CAD in CKD patients is highhigh– Patients on HD have ~40-50% prevalence Patients on HD have ~40-50% prevalence

with 9% annual CV mortalitywith 9% annual CV mortality– Renal Transplant Recipients (RTRs) have a Renal Transplant Recipients (RTRs) have a

lower CAD prevalence (15%) and annual CV lower CAD prevalence (15%) and annual CV mortality (0.54%)- Still 2X general mortality (0.54%)- Still 2X general populationpopulation

Target Target PopulationPopulation

CAD CAD Prevalence Prevalence (%)(%)

Annual CV Annual CV Mortality (%)Mortality (%)

General General PopulationPopulation

5-125-12 0.280.28

Mild-Moderate Mild-Moderate CKDCKD

------ 11

Dialysis Dialysis patientspatients

40-5040-50 99

RTR’sRTR’s 1515 0.540.54

Source: Gupta, JACC V 44 No. 7

CKD tied to Early CV eventsCKD tied to Early CV events

National Kidney Foundation study National Kidney Foundation study screened 31,417 patients “at risk” screened 31,417 patients “at risk” for CKDfor CKD– At risk defined as having HTN, DM or At risk defined as having HTN, DM or

both or were first-degree relative of both or were first-degree relative of people with HTN or DM (or both)people with HTN or DM (or both)

8/2000-12/2003 There were 560 8/2000-12/2003 There were 560 screening events in 49 states screening events in 49 states screened 18-64 YO’s (avg 47)screened 18-64 YO’s (avg 47)

69% woman, 23% had DM69% woman, 23% had DM

CKD was identified in 21% based on CKD was identified in 21% based on either albumin/creatinine ratio > 30 either albumin/creatinine ratio > 30 kg/g OR eGFR of <60 mL/min per kg/g OR eGFR of <60 mL/min per 1.73 m1.73 m22

Premature CV disease defined as a Premature CV disease defined as a H/O MI or CVA in Men <55 and H/O MI or CVA in Men <55 and Woman <65Woman <65

Other factors increasing the Other factors increasing the risk of Premature CV Diseaserisk of Premature CV Disease

Older AgeOlder Age African American raceAfrican American race DMDM HTNHTN

Prevalence of Premature Prevalence of Premature Adverse Events at 3-Year Adverse Events at 3-Year

Follow-upFollow-up

0.00%

1.00%

2.00%

3.00%

4.00%

5.00%

6.00%

MI CVA Death

CKDNo CKD

Peter McCullough, MD Poster at AHA 11/2007Peter McCullough, MD Poster at AHA 11/2007

Statistics for CVD in CKDStatistics for CVD in CKD

In dialysis patients over 75, there is a In dialysis patients over 75, there is a 5 fold increased mortality risk5 fold increased mortality risk

In patients 25-35 on dialysis, there is In patients 25-35 on dialysis, there is a 375 fold increased risk of CV a 375 fold increased risk of CV mortality!!mortality!!

In stage 5 CKD, CVA risk is 6 fold In stage 5 CKD, CVA risk is 6 fold increased and CV disease is 2 fold increased and CV disease is 2 fold increased and advances at twice the increased and advances at twice the rate over timerate over time

Cardiovascular Disease Cardiovascular Disease in in End Stage Kidney End Stage Kidney Disease Disease (Dialysis)(Dialysis)

CVD is the single best predictor of CVD is the single best predictor of mortality in patients with ESRD, mortality in patients with ESRD, and and accounts for ~50% of accounts for ~50% of deathsdeaths

Risk factors are both traditional:Risk factors are both traditional:

- DM (54%), Low HDL (33%), HTN - DM (54%), Low HDL (33%), HTN (85%), LVH (22%) and increased age (85%), LVH (22%) and increased age (average age at commencement is 60 (average age at commencement is 60 years old)years old)

Traditional risk factorsTraditional risk factors

Increasing patient ageIncreasing patient age Male sexMale sex DiabetesDiabetes SmokingSmoking HypertensionHypertension HypercholesterolemiaHypercholesterolemia

HypertensionHypertension

Complicated risk factor due to Complicated risk factor due to comorbid conditionscomorbid conditions

Low BP also portends a worsened Low BP also portends a worsened survival (perhaps a sicker population)survival (perhaps a sicker population)

Increased mortality likely driven by Increased mortality likely driven by hypertension induced LVH (with hypertension induced LVH (with studies showing that regression of studies showing that regression of LVH via BP control reduces mortality)LVH via BP control reduces mortality)– London G, J Am Soc Nephrol 2001 London G, J Am Soc Nephrol 2001

DiabetesDiabetes

Primary cause of ESRD and strongly Primary cause of ESRD and strongly associated with CV diseaseassociated with CV disease

Unique risk factors in CKDUnique risk factors in CKD

– CKD itself (independent risk factor)CKD itself (independent risk factor)– Anemia Anemia – HyperhomocysteinemiaHyperhomocysteinemia– Uremia and renal replacement therapy Uremia and renal replacement therapy

leading to oxidative stress (leading to leading to oxidative stress (leading to accelerated atherosclerosis)accelerated atherosclerosis)

– Increased plasma fibrinogen levelsIncreased plasma fibrinogen levels– Vascular CalcificationVascular Calcification

HyperhomocysteinemiaHyperhomocysteinemia

Cleared by the kidneys, thus Cleared by the kidneys, thus elevated in CKD.elevated in CKD.

Associated with deficiency in Vit B6, Associated with deficiency in Vit B6, B12 and FolateB12 and Folate

Independent risk factor for CVD in Independent risk factor for CVD in renal transplant recepients:renal transplant recepients:– Hazards ratio of 2.44Hazards ratio of 2.44

Despite risk, lowering levels has NOT Despite risk, lowering levels has NOT been shown to reduce CV mortalitybeen shown to reduce CV mortality

Abnormal NO metabolismAbnormal NO metabolism

Inhibition of Nitric Oxide synthesis is a Inhibition of Nitric Oxide synthesis is a common finding in dialysis patients.common finding in dialysis patients.– Leads to vasoconstriction, hypertension and Leads to vasoconstriction, hypertension and

adverse CV outcomesadverse CV outcomes

Asymmetrical dimethylarginine (ADMA) Asymmetrical dimethylarginine (ADMA) has been targeted for study as it is has been targeted for study as it is significantly increased in ESRD and is the significantly increased in ESRD and is the most specific endogenous compound with most specific endogenous compound with inhibitory effects on NO synthesis.inhibitory effects on NO synthesis.

CV surveillance in ESRDCV surveillance in ESRD

AllAll patients should undergo patients should undergo evaluation for CVDevaluation for CVD– Baseline ECG, Stress Test and ECHOBaseline ECG, Stress Test and ECHO

Angiography should be considered Angiography should be considered for dialysis patients with unstable for dialysis patients with unstable symptoms or positive non-invasive symptoms or positive non-invasive stress-testsstress-tests– Special attention to minimize contrast Special attention to minimize contrast

(only use iso-osmolar) (only use iso-osmolar)

Prevention of CADPrevention of CAD

Treat CKD patients as equivalent to Treat CKD patients as equivalent to prior H/O CADprior H/O CAD– Aggressive lipid loweringAggressive lipid lowering– Aggressive BP controlAggressive BP control– Surveillance of and treatment for DMSurveillance of and treatment for DM– Smoking cessationSmoking cessation– Weight lossWeight loss– Encourage daily exerciseEncourage daily exercise

Novel approaches for ESRDNovel approaches for ESRD

Vitamin E (for Vitamin E (for Homocysteine/oxidative stress Homocysteine/oxidative stress lowering)lowering)– In one trial of ~200 dialysis patients In one trial of ~200 dialysis patients

with known CAD, 800 IU/day with known CAD, 800 IU/day significantly lowered rate of MI, CVA, significantly lowered rate of MI, CVA, PAD and USA (Boaz, Lancet 2000)PAD and USA (Boaz, Lancet 2000)

Omega-3 Fatty AcidsOmega-3 Fatty Acids Correction of Anemia (goal Correction of Anemia (goal

Hemoglobin 11-12 g/dL)Hemoglobin 11-12 g/dL)

Cardiovascular Disease in Cardiovascular Disease in Renal TransplantationRenal Transplantation

The overall mortality associated with The overall mortality associated with renal transplant has been stable renal transplant has been stable since the 1960’s.since the 1960’s.

Despite a significant decrease in Despite a significant decrease in infection-related deaths, a infection-related deaths, a proportionate increase in CV deaths proportionate increase in CV deaths has occurred.has occurred.

50-60% of deaths are attributable to 50-60% of deaths are attributable to CV disease.CV disease.

Risk Factors for Atherosclerosis in RTR’s

John Vella, MD

Traditional risk factors which can be Traditional risk factors which can be exacerbated by immunosuppressive exacerbated by immunosuppressive drugsdrugs

Unique risk factors found only in Unique risk factors found only in Kidney Transplant populationKidney Transplant population

Determinants of Determinants of atherosclerosis in Renal atherosclerosis in Renal Transplant RecipientsTransplant Recipients

Unique Risk FactorsUnique Risk Factors

HyperhomocysteinemiaHyperhomocysteinemia Elevated LP (a)Elevated LP (a) Elevated CRPElevated CRP Allograft lossAllograft loss ObesityObesity RejectionRejection Vascular CalcificationsVascular Calcifications

HyperlipidemiaHyperlipidemia

Post-transplant patients are considered Post-transplant patients are considered CHD risk equivalent (target LDL<80, CHD risk equivalent (target LDL<80, Trig<200, HDL>40)Trig<200, HDL>40)

Despite advances in short-term allograft Despite advances in short-term allograft survival due to immunosupressive survival due to immunosupressive regimens, Hyperlipidemia remains a regimens, Hyperlipidemia remains a significant problem.significant problem.

Corticosteroids, Cyclosporin, Tacrolimus Corticosteroids, Cyclosporin, Tacrolimus and Rapamycin all raise serum lipids, and Rapamycin all raise serum lipids, including triglycerides.including triglycerides.

Hypertension after Renal Hypertension after Renal TransplantationTransplantation

Hypertension develops in up to 80% Hypertension develops in up to 80% of Renal allograft recipientsof Renal allograft recipients

Elevated Blood Pressure and Pulse Elevated Blood Pressure and Pulse Pressure results in decreased Pressure results in decreased allograft survival and LVHallograft survival and LVH

LVH is an independent risk factor for LVH is an independent risk factor for CHF and CV mortalityCHF and CV mortality

HypertensionHypertension

Post-transplant hypertension results in Post-transplant hypertension results in a decline in long-term allograft and a decline in long-term allograft and patient survival.patient survival.

Kidneys obtained from hypertensive Kidneys obtained from hypertensive donors result in lower graft survival donors result in lower graft survival ratesrates

Cyclosporine, Steroids and Tacrolimus Cyclosporine, Steroids and Tacrolimus (FK-506) use result in new onset or (FK-506) use result in new onset or exacerbation of hypertension.exacerbation of hypertension.

Risk factors for Post-transplant Risk factors for Post-transplant HypertensionHypertension

Delayed and/or chronic allograft Delayed and/or chronic allograft dysfunctiondysfunction

Donor with a FHX of HypertensionDonor with a FHX of Hypertension Presence of Native KidneysPresence of Native Kidneys Cyclosporine, Tacrolimus or Cyclosporine, Tacrolimus or

Corticosteroid useCorticosteroid use Renal Artery StenosisRenal Artery Stenosis ObesityObesity

Role of Donor and Recipient Role of Donor and Recipient FHXFHX

There is evidence that the There is evidence that the transplanted kidney may have either transplanted kidney may have either pro-hypertensive or anti-hypertensive pro-hypertensive or anti-hypertensive propertiesproperties

Multiple animal models suggest that Multiple animal models suggest that the inherited tendency to the inherited tendency to hypertension resides primarily in the hypertension resides primarily in the kidneykidney

In a study of 85 patients, it was In a study of 85 patients, it was found that elevations in blood found that elevations in blood pressure and increased pressure and increased antihypertensive requirements post-antihypertensive requirements post-transplant occurred much more transplant occurred much more frequently in recipients WITHOUT a frequently in recipients WITHOUT a family history of hypertension who family history of hypertension who received a kidney from a donor WITH received a kidney from a donor WITH a family history of hypertension a family history of hypertension (Guidi E, J Am Soc Nephrol 1996)(Guidi E, J Am Soc Nephrol 1996)

In a follow-up study, donor kidneys In a follow-up study, donor kidneys from patients with a family history of from patients with a family history of hypertension into a patient without a hypertension into a patient without a family history of hypertension were family history of hypertension were associated with a greater associated with a greater hypertensive response during acute hypertensive response during acute rejection compared to all other rejection compared to all other groups (Guidi, E- J Am Soc Nephrol groups (Guidi, E- J Am Soc Nephrol 1998)1998)

Role of CorticosteroidsRole of Corticosteroids

Corticosteroids have been a known Corticosteroids have been a known precipitant of hypertension in the general precipitant of hypertension in the general population for some timepopulation for some time

It has been shown that gradual withdrawal It has been shown that gradual withdrawal of corticosteroid therapy from stable renal of corticosteroid therapy from stable renal transplant recipients results in a fall in transplant recipients results in a fall in blood pressure. The effect is greatest in blood pressure. The effect is greatest in those with preexisting hypertension (Hricik those with preexisting hypertension (Hricik DE Transplantation 1992)DE Transplantation 1992)

Role of Cyclosporine and Role of Cyclosporine and TacrolimusTacrolimus

Limited data post renal Limited data post renal transplantation, but information from transplantation, but information from BMT and Cardiac Transplantation BMT and Cardiac Transplantation suggest hypertension in ~70% of suggest hypertension in ~70% of patientspatients

Combination of Tacrolimus and Combination of Tacrolimus and Sirolimus has been shown to worsen Sirolimus has been shown to worsen pre-existing hypertension (Gonwa, pre-existing hypertension (Gonwa, Transplantation 2003)Transplantation 2003)

Treatment of Post-Treatment of Post-Transplantation HypertensionTransplantation Hypertension

Reduction or elimination of offending Reduction or elimination of offending drug (in cases of immunosuppresive drug (in cases of immunosuppresive cause)cause)

Calcium Channel Blockers (particularly Calcium Channel Blockers (particularly nifedipine)nifedipine)

Diuretics with salt restricted dietDiuretics with salt restricted diet ? ACE-I/ARB—best to wait for 6 months ? ACE-I/ARB—best to wait for 6 months

if possible to avoid potential anemia if possible to avoid potential anemia and obscuring acute-rejection detection and obscuring acute-rejection detection (by mildly raising CR)(by mildly raising CR)

Renal Artery StenosisRenal Artery Stenosis

Is a significant cause of Post-Is a significant cause of Post-Transplantation hypertension, Transplantation hypertension, responsible for approximately 12-responsible for approximately 12-20% of the cases20% of the cases

Usually occurs between 3-24 months Usually occurs between 3-24 months post transplantpost transplant

Important to detect early and correctImportant to detect early and correct

Risk FactorsRisk Factors

Harvesting and operative Harvesting and operative complications (mechanical damage complications (mechanical damage from suturing or trauma)from suturing or trauma)

Atherosclerotic DiseaseAtherosclerotic Disease CMV infectionCMV infection Delayed allograft function Delayed allograft function

Features of Graft Renovascular Features of Graft Renovascular DiseaseDisease

Increased creatinine after ACE-I/ARB Increased creatinine after ACE-I/ARB administrationadministration

““Flash” Pulmonary EdemaFlash” Pulmonary Edema Uncontrolled HypertensionUncontrolled Hypertension Acute rise in Blood PressureAcute rise in Blood Pressure

Diagnostic ImagingDiagnostic Imaging

Renal Arteriography– “Gold Renal Arteriography– “Gold Standard” butStandard” but– InvasiveInvasive– Risk of dye-induced renal dysfunctionRisk of dye-induced renal dysfunction

Alternatives include:Alternatives include:– Ultrasound (highly dependent on center)Ultrasound (highly dependent on center)– MRA (caution using gadolinium with GFR MRA (caution using gadolinium with GFR

of < 30-60)of < 30-60)– CTA- most data in native kidneys, but CTA- most data in native kidneys, but

promisingpromising

Treatment Modalities for Treatment Modalities for RASRAS

PTCA successful in up to 80% of PTCA successful in up to 80% of patients, but not useful with patients, but not useful with mechanical causes (arterial kinking, mechanical causes (arterial kinking, anastomotic strictures or long lesions)anastomotic strictures or long lesions)

Surgery useful only for cases not Surgery useful only for cases not amenable to PTCAamenable to PTCA

ALERT studyALERT study AAssessment of ssessment of LLescol (fluvastatin) in escol (fluvastatin) in

RRenal enal TTransplantation (Am J Kidney Dis ransplantation (Am J Kidney Dis 2005)2005) Factors showing independent risk for MI and Factors showing independent risk for MI and

CV death included:CV death included: Preexisting CADPreexisting CAD HypercholesterolemiaHypercholesterolemia Acute rejectionAcute rejection AgeAge DMDM Elevated serum creatinine (>1.5, significant >2.3)Elevated serum creatinine (>1.5, significant >2.3)

Pre-transplant CV disease in the Pre-transplant CV disease in the single largest determinant of post-single largest determinant of post-transplant CV diseasetransplant CV disease

Pre-transplant uremic state is Pre-transplant uremic state is associated with accelerated associated with accelerated atherogenesis via atherogenesis via hyperfibrinogenemia, increased hyperfibrinogenemia, increased calcium ingestion, mineral calcium ingestion, mineral metabolism abnormalities and metabolism abnormalities and modification of LDL by glycosylation modification of LDL by glycosylation end-products (AGE) in DM.end-products (AGE) in DM.

Value of Biomarkers in Value of Biomarkers in RTR’sRTR’s

Troponin T is a central marker for Troponin T is a central marker for diagnosis, prognosis and risk-diagnosis, prognosis and risk-stratification of patients with ACSstratification of patients with ACS

It has been known that Troponin T It has been known that Troponin T elevations also occur in elevations also occur in asymptomatic patients on dialysis asymptomatic patients on dialysis and in RTR’sand in RTR’s– What role, if any does Troponin T play in What role, if any does Troponin T play in

this setting?this setting?

Connolly, Nephrology Dialysis Connolly, Nephrology Dialysis Transplant 2007Transplant 2007

372 consecutive asymptomatic RTR’s 372 consecutive asymptomatic RTR’s were recruited between 2000-2002were recruited between 2000-2002

Troponin T was measured at baseline Troponin T was measured at baseline and prospective follow-up data and prospective follow-up data collectedcollected

CV risk assessment questionnaire at CV risk assessment questionnaire at enrollment recorded traditional CV enrollment recorded traditional CV risk factorsrisk factors

Demographics: Of the 372 patients,Demographics: Of the 372 patients,– 64% Male64% Male– 19% Smokers19% Smokers– 14% DM14% DM– 22% known vascular disease at 22% known vascular disease at

enrollmentenrollment

At follow-up (median 1739 days), 311 At follow-up (median 1739 days), 311 were still alive and 61 (16%) had diedwere still alive and 61 (16%) had died– 24 died from CV disease24 died from CV disease– 28 died from non-CV disease28 died from non-CV disease– 9 other/unidentified9 other/unidentified

CV deaths

All-cause mortality

ConclusionsConclusions

Troponin T level is a strong Troponin T level is a strong independent predictor of all cause independent predictor of all cause mortality in RTR’smortality in RTR’s

Aggressive CV risk factor Aggressive CV risk factor modification should be targeted at modification should be targeted at patients with elevated Tropnin T patients with elevated Tropnin T levels.levels.

Vascular CalcificationVascular Calcification

Presence of vascular calcifications Presence of vascular calcifications detected radiographically by CT detected radiographically by CT (particularly Coronary Artery (particularly Coronary Artery Calcification) pre-transplant is a major Calcification) pre-transplant is a major risk factor for CVD post-transplant.risk factor for CVD post-transplant.

Presence of CAC is associated with Presence of CAC is associated with calcium supplementaion, CA-calcium supplementaion, CA-containing Oral Phosphate Binders, containing Oral Phosphate Binders, Vitamin D therapy, increasing age and Vitamin D therapy, increasing age and length of dialysis. length of dialysis.

-Medial deposition is more common, -Medial deposition is more common, associated with vascular stiffness associated with vascular stiffness resulting in downstream CV disease.resulting in downstream CV disease.-Intimal deposition is less common, -Intimal deposition is less common, and although clearly associated with and although clearly associated with CVD in patients with normal renal CVD in patients with normal renal function its role CKD patients is function its role CKD patients is unclear. It is associated with plaque unclear. It is associated with plaque vulnerability and rupture.vulnerability and rupture.

Two types of VC: medial and Two types of VC: medial and intimal deposition.intimal deposition.

Implications of VCImplications of VC

Increased stiffness of large conduit Increased stiffness of large conduit arteries resulting in increased pulse arteries resulting in increased pulse pressure, reduced coronary perfusion pressure, reduced coronary perfusion and impaired endothelial function.and impaired endothelial function.

Impact on smaller arteries include Impact on smaller arteries include vascular anastomoses failure and vascular anastomoses failure and difficulty with coronary artery difficulty with coronary artery interventions (PTCA, Stenting and interventions (PTCA, Stenting and CABG).CABG).

Detection and Treatment of Detection and Treatment of Vascular CalcificationVascular Calcification

Detection of VCDetection of VC

CT scanning is gold standard CT scanning is gold standard because it permits both detection because it permits both detection and quantification of VC (although and quantification of VC (although does not distinguish between does not distinguish between medial/intimal).medial/intimal).

Plain films and Vascular ultrasound Plain films and Vascular ultrasound sometimes helpful.sometimes helpful.

Treatment and PreventionTreatment and Prevention

Avoidance of marked or prolonged Avoidance of marked or prolonged positive calcium balance.positive calcium balance.– Minimize Ca++ supplementationMinimize Ca++ supplementation– Avoid Vitamin D useAvoid Vitamin D use– Use Non-Calcium based phosphate Use Non-Calcium based phosphate

bindersbinders Aggressive Statin use to lower LDLAggressive Statin use to lower LDL ? Early Transplantation for ESRD? Early Transplantation for ESRD

Case StudiesCase Studies

Case 1Case 1

Pre-Transplant CV evaluationPre-Transplant CV evaluation

HistoryHistory PEPE ECGECG CXRCXR Non-Invasive CV testing (patients Non-Invasive CV testing (patients

with signs/symptoms of CAD or with signs/symptoms of CAD or multiple traditional risk factors)multiple traditional risk factors)

Angiography for H/O CAD, DM or Angiography for H/O CAD, DM or High risk of CAD (caution with dye High risk of CAD (caution with dye and volume use)and volume use)

Types of Non-Invasive Types of Non-Invasive studiesstudies

Stress ECHOStress ECHO Dobutamine ECHODobutamine ECHO Nuclear StressNuclear Stress

-The determination of which strategy -The determination of which strategy to use is dependent on the expertise to use is dependent on the expertise of the individual center.of the individual center.

Case 1Case 1

Is a negative DSE enough?Is a negative DSE enough?

Paucity of data exists regarding the Paucity of data exists regarding the effectiveness of risk-stratification for effectiveness of risk-stratification for

CVD pre-transplantCVD pre-transplant

The largest study looked at outcomes of The largest study looked at outcomes of 514 consecutive patients (Kasiske, 514 consecutive patients (Kasiske, Transplantation 2005)Transplantation 2005)– Stratified into low and high risk groups based Stratified into low and high risk groups based

on clinical features:on clinical features:

High risk– DM, H/O or symptoms of CAD, High risk– DM, H/O or symptoms of CAD, Multiple Multiple risk factors (age >45, smoking, risk factors (age >45, smoking, hyperlipidemia, hyperlipidemia, HTN, CVA, PAD)HTN, CVA, PAD)

Low risk– everyone else (~44% of group)Low risk– everyone else (~44% of group)

Low Risk (44%)Low Risk (44%)

Proceeded to transplantation Proceeded to transplantation WITHOUT further testingWITHOUT further testing

High Risk (56%)High Risk (56%)

Underwent Noninvasive testing and Underwent Noninvasive testing and examination by a Cardiologistexamination by a Cardiologist

If stress test was positive If stress test was positive angiography and subsequent angiography and subsequent PCI/CABG were appropriatePCI/CABG were appropriate

ResultsResults

Among the High risk group, PCI was Among the High risk group, PCI was performed 6.2% and CABG 3%performed 6.2% and CABG 3%

For those on the waitlist, 25 low risk For those on the waitlist, 25 low risk and 36 high risk were tested/retested and 36 high risk were tested/retested resulting in 6 PCI’s and 1 CABG.resulting in 6 PCI’s and 1 CABG.

Among the Low risk group, incidence Among the Low risk group, incidence of CV events after waitlisting was low of CV events after waitlisting was low (0.5%, 3.5% and 5.3% for 1, 3 and 5 (0.5%, 3.5% and 5.3% for 1, 3 and 5 years respectively-includes pre and years respectively-includes pre and post)post)

2005 Canadian Society for 2005 Canadian Society for TransplantationTransplantation

Based on this study, the guidelines Based on this study, the guidelines were revised to indicate that those were revised to indicate that those eligible for kidney transplantation are:eligible for kidney transplantation are:– Asymptomatic low risk patients, including Asymptomatic low risk patients, including

those with negative non-invasive testingthose with negative non-invasive testing– Patients with non-critical CAD on Patients with non-critical CAD on

angiography maintained with appropriate angiography maintained with appropriate medical therapymedical therapy

– Patients S/P successful PCI/CABGPatients S/P successful PCI/CABG

Case 1Case 1

Thrombolysis, when is it safe?Thrombolysis, when is it safe?

Although it is still unclear whether Although it is still unclear whether CKD patients with an STEMI obtain CKD patients with an STEMI obtain the same benefit with thrombolytics the same benefit with thrombolytics as those with normal renal functions as those with normal renal functions (most trials excluded CR > 1.5 (most trials excluded CR > 1.5 gm/dL), they should be used when gm/dL), they should be used when needed.needed.

– Two studies have looked at this issue:Two studies have looked at this issue: Sorrell (Semin Nephrol 2001)Sorrell (Semin Nephrol 2001) Fernandez (Am J Kidney Dis 2003)Fernandez (Am J Kidney Dis 2003)

If possible, Primary PCI are the If possible, Primary PCI are the preferred modality in most patients preferred modality in most patients with STEMI with CABG if necessarywith STEMI with CABG if necessary– Need to be mindful of CINNeed to be mindful of CIN

Even with the best care, mortality Even with the best care, mortality after CABG and complication rate after CABG and complication rate after PCI are increased in patients after PCI are increased in patients with CKDwith CKD– Risk of in-hospital mortality after CABG Risk of in-hospital mortality after CABG

was markedly increased compared to was markedly increased compared to non-CKD (odds ratio 3.38) Charytan, non-CKD (odds ratio 3.38) Charytan, Nephrol Dial Transplant 2007.Nephrol Dial Transplant 2007.

Case 2Case 2

Renal Transplantation in patients Renal Transplantation in patients with Aortic Stenosiswith Aortic Stenosis

Post-Op monitoring issuesPost-Op monitoring issues

Valvular disease is common in CKD Valvular disease is common in CKD populationpopulation

Occurs as a consequence of Occurs as a consequence of secondary hyperparathyroidism with secondary hyperparathyroidism with associated VC, hypercalcemia and associated VC, hypercalcemia and hyperphospatemiahyperphospatemia

Other risk factors include:Other risk factors include:– HTNHTN– DMDM– AnemiaAnemia– High CO stateHigh CO state

Valvular ASValvular AS

Most common obstructive Most common obstructive abnormality among hemodialysis abnormality among hemodialysis population with a prevalence of 15-population with a prevalence of 15-20%20%

Hemodynamically significant AS Hemodynamically significant AS occurs in ~7% of HD patientsoccurs in ~7% of HD patients

Track AS yearly with ECHOTrack AS yearly with ECHO

Pre-operatively (on dialysis)- careful Pre-operatively (on dialysis)- careful ultrafiltration to avoid reduction of ultrafiltration to avoid reduction of end diastolic filling pressuresend diastolic filling pressures

Post-operatively – avoid dehydration, Post-operatively – avoid dehydration, tachycardia, anemia and diureticstachycardia, anemia and diuretics

Issue 1Issue 1

CV evaluation in chronic dialysis CV evaluation in chronic dialysis patientspatients– Addressed previously, patients are Addressed previously, patients are

treated as being equivalent to CAD treated as being equivalent to CAD patients in terms of HTN, Lipids and DM patients in terms of HTN, Lipids and DM surveillance and treatmentsurveillance and treatment

– Regular H/P, Labs, ECG and Non-invasive Regular H/P, Labs, ECG and Non-invasive Stress testingStress testing

– Angiography for high risk, symptomatic Angiography for high risk, symptomatic patients or positive non-invasive testingpatients or positive non-invasive testing

Issue 2Issue 2

Are patients with CHF Are patients with CHF candidates candidates for for transplant?transplant?

CHF in ESRDCHF in ESRD

Both systolic and diastolic function is Both systolic and diastolic function is impaired with ESRDimpaired with ESRD

Prevalence of CHF is 10-30 fold Prevalence of CHF is 10-30 fold higher among dialysis patients than higher among dialysis patients than in the general populationin the general population

LV dysfunction is not necessarily a LV dysfunction is not necessarily a contraindication to kidney contraindication to kidney transplantation.transplantation.

Uremic CHF may actually improve post-Uremic CHF may actually improve post-transplantationtransplantation

Patients with a severe (non-uremic) CM, Patients with a severe (non-uremic) CM, should generally not be listed for renal should generally not be listed for renal transplant alone (perhaps combined transplant alone (perhaps combined heart-kidney in selected patients?)heart-kidney in selected patients?)

Effect of Kidney Effect of Kidney Transplantation on LVSD and Transplantation on LVSD and

CHF in ESRDCHF in ESRD Wali, JACC 2005Wali, JACC 2005

Followed 103 patients with Followed 103 patients with EF<40% and CHF post-EF<40% and CHF post-

transplanttransplant Conclusions:Conclusions:

– Kidney transplantation resulted in Kidney transplantation resulted in increased LVEF, improved NYHA increased LVEF, improved NYHA functional class and survival (but only functional class and survival (but only for the group that had a post-transplant for the group that had a post-transplant LVEF >50%)LVEF >50%)

– There were no perioperative deathsThere were no perioperative deaths– At 1 year, the mean LVEF increased At 1 year, the mean LVEF increased

from 32% to 52%from 32% to 52%

More than 2/3 of patients achieved More than 2/3 of patients achieved an LVEF of >50an LVEF of >50

Renal transplant should be Renal transplant should be considered as early as possible, as considered as early as possible, as prolonged dialysis worsens uremic-prolonged dialysis worsens uremic-induced CHF and outcomes after induced CHF and outcomes after transplantationtransplantation