Editorial
The Cost of Screening Kidney Transplant Candidates
for Coronary Artery Disease
Allyson Hart, Krista L. Lentine, and Bertram L. Kasiske
D uring the past 20 years, the recognition that most
patient groups with kidney failure experience survival
and quality-of-life benefits with transplantation versus
dialysis has resulted in increasing medical complexity and
Related Article, p. 693
comorbid condition burden among the population seeking
evaluation for and awaiting kidney transplantation.1,2
Given the markedly increased risk for cardiovascular dis-
ease in patients with chronic kidney disease (CKD) and the
high prevalence of additional cardiovascular risk factors
such as diabetes, screening asymptomatic patients for
coronary artery disease (CAD) before transplantation may
appear on its face to be a logical step in the evaluation of
potential candidates. Detecting and intervening on CAD
pre-emptively could theoretically improve outcomes
through the detection and treatment of CAD before
transplantation. Pre-emptive detection might thereby
reduce the risk for both perioperative and subsequent
major adverse cardiac events, as well as theoretically
improve the utility of transplantation by allocating scarce
organs to patients who may benefit the most. Such logic
has led to clinical practice guideline recommendations
based on expert opinion pending definitive trial evi-
dence.3-5
Unfortunately, the medical utility of CAD screening and
surveillance among kidney transplant candidates is un-
proved. Evidence against routine screening of asymptom-
atic candidates seems to be incrementally building, albeit
slowly. In patients without advanced CKD, randomized
trials have found no benefits of prophylactic screening or
revascularization of stable CAD, even in high-risk patients
such as those undergoing vascular surgery.6-8 In addition,
potential harms associated with screening and subsequent
cardiovascular procedures are not trivial, including delays
accessing the waitlist and lower likelihood of listing and
transplantation. The economic cost benefit of screening is
increasingly recognized as critical to both clinical practice
guidelines and reimbursement and has also been unclear to
date.
Two randomized controlled trials may have a substan-
tial impact on the approach to cardiac evaluation of po-
tential kidney transplant candidates. CARSK (Canadian
Australasian Randomized Trial of Screening Kidney
Transplant Candidates for CAD), the subject of the
modeled cost-benefit analysis from Ying et al9 in this issue
of AJKD, will likely not be completed until 2025. CARSK is
randomly allocating patients being evaluated for deceased
donor transplantation or already on the kidney transplant
684
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waiting list to periodic screening for CAD (usual care)
versus no CAD screening.10 Whether screening candidates
before placing them on the waiting list is beneficial is not
addressed.
However, in November 2019, the preliminary results
from the ISCHEMIA-CKD (International Study of
Comparative Health Effectiveness With Medical and Inva-
sive Approaches—CKD) Trial were presented at the annual
meeting of the American Heart Association. The
ISCHEMIA-CKD Trial randomly allocated patients with
stable ischemic heart disease, at least moderate inducible
ischemia, and advanced CKD (estimated glomerular
filtration rate < 30 mL/min/1.73 m2 or receiving dialysis)
to optimal medical therapy plus cardiac catheterization and
revascularization, if indicated, versus optimal medical
therapy alone.11 Most patients included in the ISCHEMIA-
CKD Trial were undergoing evaluation for kidney trans-
plantation. Results showed that there were no reductions
in death or nonfatal myocardial infarction with revascu-
larization compared with optimal medical management.
Interestingly, the incidence of strokes was higher in the
revascularization arm compared to optimal medical man-
agement alone, although the number of strokes was very
small. The transplantation community eagerly awaits the
publication of detailed results from this important study.
Ying et al provide evidence to help address the notable
knowledge gap in the cost-effectiveness of cardiac sur-
veillance of transplant candidates by describing a modeled
cost-benefit analysis of ongoing regular screening of can-
didates for asymptomatic CAD versus no additional
screening among a theoretical cohort of adult Australian
and New Zealand kidney transplant candidates already on
the waitlist. The investigators developed a microsimulation
model to replicate the natural history of a theoretical
cohort over their remaining lifetime and drew estimates of
clinical events, costs, and utilities from sources including
the literature, the Australian and New Zealand Dialysis and
Transplantation Registry (ANZDATA), and the Medicare
Benefits Schedule.
Total lifetime costs after entry onto the waitlist were
higher for no further screening at $506,092 compared
with $502,288 for regular screening. The higher cost may
seem surprising but likely accrued because regular
screening was associated with higher mortality in this
model (26.0% vs 24.8%), possibly due to risks of invasive
cardiac procedures and, importantly, longer time on the
waitlist. It is typical in cost-benefit analyses that in-
terventions increasing longevity increase cost and vice
versa. No further screening increased life-years by 0.49
year on average, from 8.89 to 9.38 years, and increased
AJKD Vol 75 | Iss 5 | May 2020
Editorial

quality-adjusted life-years by 0.35 year, from 7.31 to
7.67 years. In addition, a higher proportion of patients
in the no-further-screening arm received a transplant
after 5 years compared with the regular screening arm
(65% vs 63%).
It is important to note that the analysis and conclusions
of Ying et al rest on 2 key assumptions. First, that high-risk
asymptomatic patients were already screened for CAD as a
condition for waitlist registration. This assumption
matches the design of CARSK, but does not address the
question as to whether it is appropriate to screen these
patients to begin with as a condition of waitlisting. To
date, only 1 trial in transplant candidates, by Manske et al12
in 1992, has directly addressed this question, and its small
size and conduct in a different treatment era make it
difficult to draw contemporary conclusions.
The second assumption of this analysis is that ongoing
screening for CAD among asymptomatic patients confers
no benefit in survival. Although this assumption is
reasonable based on the data available, it again highlights
the need for randomized controlled trials to assess whether
this near-universal practice is warranted for any outcomes,
whether one is interested in mortality, quality of life, or
economic burden. The modeling conclusions persisted in
sensitivity analyses in which nonfatal myocardial infarction
in the no-further-screening arm was increased by up to
50%. The results of CARSK will provide vital evidence to
strengthen the evidence base for the clinical and cost-
effectiveness of CAD surveillance on the waiting list.
However, importantly, CARSK excludes some patients
at the highest level of risk for CAD, such as kidney-
pancreas transplant candidates, among whom both clin-
ical outcomes and costs may differ from those among
lower-risk candidates. CARSK also does not include many
candidates who are low risk for CAD, for example, those
anticipated to undergo living donor transplantation. Ulti-
mately, when the results of CARSK are reported, it will be
important to conduct a cost-benefit analysis based on the
actual data and to weigh the impact of the numbers of
patients excluded or electing not to participate.
Although patients with advanced CKD experience a
higher burden of cardiovascular disease than the general
population,13 the sensitivity and specificity of tests for
obstructive CAD are limited in this population.14,15
Furthermore, the benefit of revascularization among
those with obstructive CAD remains unproved.3 In light
of this paucity of evidence, the routine practice of
screening asymptomatic transplant candidates without
evidence to support the practice is weak and guidelines
committees have struggled with how to approach rec-
ommendations for pretransplantation cardiac evaluations.
Since 1995, guidelines from Europe, Canada, and
the United States, as well as from renal, cardiology,
and transplantation organizations, have all suggested
screening asymptomatic patients for CAD before listing
while acknowledging that the evidence supporting this
suggestion is minimal. Detailed clinical history and
physical examinations may yet be the best way to detect
the minority of asymptomatic patients with occult high-
risk coronary anatomy, such as significant left main dis-
ease or severe proximal 3-vessel disease, who might truly
benefit from preoperative revascularization.
In an era of increasing health care costs and focus on
evidence-based medicine, ongoing routine screening of
asymptomatic transplant candidates represents a large gap
in evidence-based practice. The outcomes of CARSK and
the ISCHEMIA-CKD Trial will help elucidate the benefits
and risks of screening on survival, quality of life, and cost.
However, these trials will leave questions pertinent to the
management of candidates not yet waitlisted for a

The Problem The Soluon The Evidence

Does RCTs in high-risk stable
screening paents from the general
CAD – most common asymptomac populaon have not
cause of death with gra KTx candidates reported ↓ deaths or
funcon (wasng lives prevent nonfatal MI
and donor kidneys) CAD-related
morbidity & RCTs in KTx candidates
mortality? pending

Is screening Cost-ulity analyses

cost-effecve?

Implement evidence-
based clinical pracce
guideline!

Figure 1. A conceptual model of evidence, guidelines, and needs to inform cardiovascular risk assessment and management among
high-risk kidney transplant candidates. Abbreviations: CAD, coronary artery disease; KTx, kidney transplant; MI, myocardial infarction;
RCT, randomized controlled trial.

AJKD Vol 75 | Iss 5 | May 2020 685

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transplant, the impact of regional differences in waitlist
outcomes and cost, and the management of very high-risk
asymptomatic patients. The evidence available, as well as
the universal screening practice despite weak supporting
evidence, suggest a need for additional studies and data
collection, conceptualized in Figure 1. In the meantime,
considerations for maximizing the utility of transplantation
as a scarce resource must be distinguished from optimizing
the care of individual transplant candidates, most of whom
are much more likely to derive benefit from trans-
plantation, regardless of the presence of CAD, compared
with remaining on dialysis.
Article Information
Authors’ Full Names and Academic Degrees: Allyson Hart, MD,
MS, Krista L. Lentine, MD, PhD, and Bertram L. Kasiske, MD.
Authors’ Affiliations: Hennepin Healthcare, Minneapolis, MN (AH,
BLK); and Saint Louis University Transplant Center, St. Louis, MO
(KLL).
Address for Correspondence: Allyson Hart, MD, MS, Hennepin
Healthcare, 701 Park Ave, Nephrology Ste S5, Minneapolis, MN
55415. E-mail: hart1044@umn.edu
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Peer Review: Received November 19, 2019, in response to an
invitation from the journal. Accepted November 19, 2019, after
editorial review by a Deputy Editor.
Publication Information: © 2019 by the National Kidney Founda-
tion, Inc. Published online January 31, 2020 with doi 10.1053/
j.ajkd.2019.11.003
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Editorial
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