Cardiovascular Screening and Management Among Kidney Transplant
Candidates in Hungary
R.P. Szabóa,d,*, I. Vargab, J. Ballaa,c, L. Zsomd, and B. Nemesd
a
FMC Debrecen, Extracorporal Organsupport Centre, University of Debrecen, Debrecen, Hungary; bInstitute of Cardiology, University of
Debrecen, Debrecen, Hungary; c1st Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of
Debrecen, Debrecen, Hungary; and dInstitute of Surgery, Division of Transplantation, University of Debrecen, Debrecen, Hungary
ABSTRACT
Introduction. Cardiovascular disease is a major cause of morbidity and mortality in endstage renal disease patients on dialysis and the most common cause of death in the
immediate post-transplantation period. The aim of our study was to describe a novel
approach of cardiovascular screening and management of dialysis patients evaluated for
the transplant waiting list.
Methods. Twenty-eight patients with end-stage renal disease put on the waiting list
between July 2013 and July 2014 were subjected to a prespecified cardiovascular
screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently
divided into 3 strata in terms of their estimated cardiovascular risk. Each of these
groups were then prescribed interventions aiming to improve their cardiovascular
condition.
Results. According to our prespecified protocol of cardiovascular screening studies, 15
(54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk.
Four (14%) patients were current smokers. In the low-risk group, we initiated a patient
education program involving counseling on regular exercise such as swimming or cycling
to improve their functional capacity. In the high-risk group revascularization was done in
5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA)
with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG)
for triple-vessel disease in 2 cases. In the medium-risk group medical management was
opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as
well as efforts to optimize anemia management, indices of bone-mineral disease, and
fluid status.
Conclusion. In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular
risk stratification based on a prespecified screening protocol. Further studies are needed to
correlate this novel strategy with post-transplantation outcomes.
C
ARDIOVASCULAR DISEASE (CVD) is a significant
cause of morbidity and mortality for wait-listed kidney
transplant candidates, and it is the most common cause of
death in transplant recipients. The risk of a major adverse
cardiac event (MACE) is relatively constant while on the
waiting list, then rises markedly in the early posttransplantation period, and declines to a lower rate thereafter. Understandably, clinicians are highly motivated to
screen for CVD before transplantation, hoping to prevent
events early after transplantation and to improve long-term
outcomes [1e4]. Asymptomatic chronic kidney disease
(CKD) patients often have significant coronary artery
*Address correspondence to Réka P. Szabó, MD, FMC
Debrecen, Extracorporal Organsupport Centre, University of
Debrecen, 4012, Debrecen, Nagyerdei körút 98, Hungary. E-mail:
rpszabo@belklinika.com
0041-1345/15
http://dx.doi.org/10.1016/j.transproceed.2015.07.018
ª 2015 by Elsevier Inc. All rights reserved.
360 Park Avenue South, New York, NY 10010-1710
2192
Transplantation Proceedings, 47, 2192e2195 (2015)
CARDIO SCREENING OF KIDNEY TX CANDIDATES
disease (CAD), with prevalence estimates of 37% to 53%
for at least 1 coronary artery with 50% or greater stenosis.
This high prevalence of asymptomatic CAD presents a
compelling argument for screening transplant candidates
with prior CAD, older age, or those with diabetes, to
identify asymptomatic patients who may benefit from
preemptive coronary revascularization, both to improve
perioperative MACE and to improve the long-term outcomes after transplantation [5e7]. It has also been argued
that screening can be used to exclude high-risk individuals
from transplantation and thereby protect a scarce
resource. Finally, screening low-risk patients may identify
those who would benefit most from risk-factor intervention. Although the potential benefits of screening are
compelling, they must be cost-effective and outweigh the
potential for harm. This is particularly challenging in the
CKD population, where a high proportion of patients have
noncoronary CVD and the sensitivity and specificity of
testing for CAD may be less than that in the general
population. Testing for CAD may include noninvasive
measures such as myocardial perfusion studies (MPS),
dobutamine stress echocardiograms (DSE), biomarkers, or
cardiac computed tomography (CT) followed by evaluation
with coronary angiography. Any screening test should be
cost-effective, with benefits outweighing harm. Specifically,
testing must improve outcomes of importance to patients,
not consume resources that would be better spent in other
ways, and not produce harm that outweighs the benefits
[8,9]. In the absence of randomized controlled trials
(RCTs), the optimal method, or even the benefit, of pretransplant screening and intervention, remains unclear.
The burning issue is the lack of clear guidelines as well as
the fact that in patients with low probability of CVD, many
screening procedures would be unnecessary and could
yield many false-positive results. It should be stressed that
the condition of a patient who has been on the waiting list
for transplantation for several years is not the same as it
was at the moment of evaluation and, therefore, reevaluation is needed [10]. In the published studies, patients with
CKD and transplant recipients were either excluded or
underrepresented. In the published studies, patients with
CKD were either excluded or underrepresented. Many
physicians fear prescribing cardioprotective drugs due to
their side effects, which could be aggravated by the
hematologic, metabolic, and endocrinologic abnormalities
present in CKD. Only 1 RCT seemed to show an
improvement in outcomes after revascularization vs medical management in diabetic patients before renal transplantation [11]. But this trial is difficult to interpret,
because it was small and had suboptimal use of aspirin.
Several observational studies have reported outcomes after
revascularization in selected cohorts of potential kidney
transplantation candidates, ranging from nonsignificant to
survival benefit only in patients with 3-vessel CAD to
excellent survival in transplant recipients who received
preemptive revascularization [12]. Risk factors for coronary heart disease (CHD) in the general population are
2193
also risk factors for kidney transplant patients. However,
risk-prediction defined and validated for the general population underestimates the CHD risk for kidney transplant
patients, and several nontraditional, transplant-dependent
risk factors are reported to be associated with CHD after
kidney transplantation [13e16].
METHODS
Selection and Description of Participants
Detailed clinical and demographic data were collected from the
initial transplant assessment. All candidates underwent a structured medical assessment by a consistent group of transplant
physicians before activating the transplant waiting list. This
assessment included a medical history, physical examination, lipid
profile, fasting glycemia, resting electrocardiogram (ECG) and
chest radiograph, and cardiac ultrasound. All 28 study patients
were interviewed by a cardiologist to determine the presence of
cardiovascular disease and assess the perioperative cardiovascular
risk. We put our patients on a wait list between July 2013 and
July 2014.
Classification of Cardiac Risk
Patients were classified into 3 groups according to their risk, on the
basis of the following 3 factors: age, history of diabetes, or ischemic
heart disease [17,18]. High-risk patients (n ¼ 8) displayed active
ischemic heart disease at age older than 45 years in men and over 55
years in women with a history of diabetes mellitus. Intermediaterisk patients (n ¼ 5) of age older than 45 years in men and 55
years in woman had diabetes mellitus or an abnormal baseline
ECG. Low-risk patients (n ¼ 15) had no risk factors.
Cardiovascular Screening
All patients underwent a clinical assessment that included a history,
physical examination, chest radiograph, 12-lead ECG, and transthoracic echocardiogram. An exercise stress test was performed on
all low-risk patients with normal ECG; those who tested positive
underwent coronary angiography. Myocardial perfusion imaging
was performed in patients with intermediate risk or with low risk
and abnormal baseline ECG (left bundle branch block, left ventricular hypertrophy, or ST changes, inadequate exercise stress test).
Coronary angiograms were performed on all high-risk patients and
on patients with positive myocardial perfusion imaging or positive
stress tests.
Definitions
Ischemic heart disease was defined as a history of myocardial
infarction, CABG, PTCA, or the presence of ischemia on thallium
with exercise. Perfusion imaging findings were classified as normal if
no perfusion abnormalities were present at rest or with exercise;
mild if there was decreased uptake in 2 segments or less; moderate
if there was decreased uptake in 3 to 5 segments; and severe if there
were abnormalities in more than 5 segments.
Statistics
Descriptive statistics in the form of median values and ranges for
interval variables as well as mean values standard deviation (SD)
and frequencies (percentages) for categorical variables were performed using the SPSS 14.0 statistical package (SPSS Inc., Chicago,
Ill., United States).
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SZABÓ, VARGA, BALLA ET AL
RESULTS
Baseline Clinical Characteristics
We put 28 new patients on the wait list between July 2013
and July 2014. In total, 46 patients were waitlisted at our
center (hemodialysis: 15%, peritoneal dialysis: 50%, preemptive: 2.3%). The age range of patients was 14 to 73 years
(median: 43.6 years). Eight patients in our study population
were older than 60 years, 67% were male, and 40% were
diabetic, with diabetes mellitus as the leading cause of endstage renal disease. According to our prespecified protocol,
15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four patients (14%) were
current smokers. In the low-risk group, we initiated a patient
education program involving counseling on regular exercise
such as swimming or cycling to improve patients’ functional
capacity. In the medium-risk group, we opted for medical
management, including introduction of beta-blockers,
angiotensin-converting enzyme inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management,
indices of bone-mineral disease, and fluid status. In the highrisk group, revascularization was done in 5 cases (63%),
including 3 PTCAs with stents for single-vessel disease, and
CABG for triple-vessel disease in 2 cases (Table 1).
DISCUSSION
CVD is the leading cause of morbidity and mortality in patients
on renal replacement therapy, including kidney transplant
Table 1. Patient Characteristics, Use of Cardioprotective
Medications in All Study Patients and According to Cardiac Risk
Characteristic
Low
Cardiac
Risk
No of patients
15
Age (y SD)
42 12
Months of dialysis exposure
2.5
before transplant waiting
listing
Treatment modality
Hemodialysis
3
Peritoneal dialysis
10
Combined (PD + HD)
0
Predialysis
2
Cardiac investigations
at transplant
assessment
ECG
15
Normal noninvasive
12
cardiac investigation
Abnormal noninvasive
3
cardiac investigation
Invasive cardiac
0
investigation/intervention
Cardioprotective medication use
ACE inhibitor
10 (66%)
b-blockers
8 (53%)
Lipid-lowering medication
3 (20%)
ASA or thienopyridines
4 (26%)
Intermediate
Risk
High
Cardiac
Risk
5
51 6
17.4
8
65 8
13
3
2
0
0
4
2
0
2
5
2
8
3
1
5
1
5
4 (80%)
4 (80%)
5 (100%)
3 (60%)
8 (100%)
6 (75%)
8 (100%)
8 (100%)
recipients. Death from CVD is also the most common cause of
graft loss [17e19]. The goals of cardiac evaluation include
assistance in determination of transplant candidacy and
identification of patients who might benefit form preoperative
cardiac intervention (e.g. PTCA, CABG), and aggressive risk
factor modification to decrease perioperative and posttransplantation cardiovascular events. This is particularly
important in diabetic patients, as they are at very high risk for
development of CVD. Typically evaluation starts with detailed
anamnesis, careful physical examination, ECG, and chest
radiograph. ECG is a basic method used to select candidates
for invasive diagnostics, and we suggest trying to reach target
hemoglobin level (erythropoietin, ferrous supplementation)
before ECG to avoid negative ST or T waves coming from a
low hemoglobin level. Cardiac ultrasound should be performed after a hemodialysis session (or normovolemic state in
PD patients) to avoid the influence on hypervolemia. Because
cardiovascular screening and the treatment practices of many
transplant programs were highly variable and inconsistent with
published guidelines, the American College of Cardiology/
American Heart Association worked with representatives of
the American Society of Transplant Surgeons, the American
Society of Transplantation, and the National Kidney Foundation to develop a consensus document titled “Cardiac Disease Evaluation and Management Among Kidney and Liver
Transplantation Candidates” [20]. In 2014, 2 guidelines, which
may be at least partly relevant to cardiac evaluation of potential kidney transplant recipients, were published by the
European Society of Cardiology (ESC). The new 2014 ESC/
European Society of Anesthesiology (ESA) guidelines on
noncardiac surgery: cardiovascular assessment and management by the Joint Task Force on Non-Cardiac Surgery: Cardiovascular Assessment and Management of the ESC/ESA
assess the surgical risk of patients undergoing kidney transplantation as intermediate (1e5%) [21].
In summary, organ transplantation often is the only
effective treatment for patients with end-stage organ failure.
Kidney transplant requirements vary from program to program and country to country. Due to the scarcity of organs
for transplantation, careful evaluation of potential transplant recipients is the priority. Detailed cardiac evaluation is
of prime importance to ensure the best possible outcomes.
In this situation, a multidisciplinary approach is required
(cardiologist, anesthesiologist, hematologist, nephrologist,
and surgeon) to determine the patient’s risk and choose the
best strategy. In our regional transplant program, we
introduced a comprehensive multidisciplinary approach to
treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening
protocol. Further studies are needed to correlate this novel
strategy with post-transplantation outcomes.
ACKNOWLEDGMENTS
We thank the transplantation team of the Institute of Surgery,
Centre of Transplantation, University of Debrecen, and the Institute of Cardiology for their collaboration.
CARDIO SCREENING OF KIDNEY TX CANDIDATES
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