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Intervention associated Acute Kidney Injury and long-term cardiovascular outcomes
Athanasios Saratzis1, Seamus Harrison1, Jonathan Barratt2, Robert D. Sayers1, Pantelis
Sarafidis3, Matthew J. Bown1
1
Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical
Research Unit, University of Leicester, Leicester Royal Infirmary, Leicester, United
Kingdom
2
Department of Infection, Immunity & Inflammation, University of Leicester, Leicester,
United Kingdom
3
Department of Nephrology, Aristotle University, Greece
Corresponding author:
Athanasios Saratzis
NIHR Academic Clinical Lecturer – Vascular Surgery
Department of Cardiovascular Sciences & Biomedical Research Unit
University of Leicester
Leicester Royal Infirmary
LE15WW
E-mail: [email protected]
Telephone: (0044) 07531418104
Word count: 5,000 with references included
Number of tables: 4 and 3 as supplements
Number of figures: 1 and 1 as supplement
No colour figures
Short title: AKI and cardiovascular events
Keywords: Acute Kidney Injury, Acute Renal Failure, Cardiovascular, Outcomes, Risk
factors
Authors have no conflict of interest.
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ABSTRACT
Background: AKI has been associated with all-cause short and long-term mortality.
However, the association with CV-events remains unclear. We sought to investigate this in
patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm (AAA)
repair, as they are likely to develop both AKI and CV-morbidity. A meta-analysis was
subsequently performed to confirm this in other cardiovascular-interventions.
Methods: AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing
EVAR (947 individuals) or OAR electively using the “Acute Kidney Injury Network”
criteria. A composite-endpoint was used, consisting of: non-fatal myocardial infarction (MI),
stroke, vascular event, hospitalisation due to heart-failure and CV-death. A systematic
literature review identified studies reporting AKI-incidence and CV-events. Risk-ratios at 1
and 5 years were combined using meta-analysis.
Results: During a median follow-up of 62 months (range: 11-121) AKI was associated with
CV-events on adjusted (for cardiovascular risk-factors) analyses [Incidence: 36% of EVAR,
32% of OAR patients; Hazard Ratio 1.73, 95% CI 1.06-3.39, p=0.03] for the overall
population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year
after coronary-intervention (PCI) with a pooled risk-ratio (RR) of 1.76 (95%CI: 1.45-2.83,
p<0.001); at 2-years, 3 studies reported MI-incidence on 17,773 patients after PCI with a
pooled RR of 1.34 (95%CI: 1.10-1.63, p=0.003). MI-incidence was reported 5 years after
cardiac-surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95%CI: 1.43-1.81).
Conclusion: AKI is associated with long-term CV events after surgery or endovascular
intervention.
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No funding has been received for the specific analysis and there are no financial
arrangements between any author and any company whose product or competing product
plays a prominent role in this manuscript. The results have not been published previously.
INTRODUCTION
Acute kidney injury (AKI) can present in up to 20% of individuals undergoing cardiovascular
(CV) intervention[1]. Development of AKI has been associated with short-term morbidity,
hospital-stay, treatment-cost, and mortality[2]. AKI has also been associated with long-term
mortality after surgery [3,4]and has been estimated [5] to cost the NHS £620 million
annually. A significant proportion of adverse events in populations with AKI are attributable
to CV morbidity[4,6]. However, the exact association between AKI and long-term
cardiovascular events has not been fully investigated.
A typical population at high-risk for AKI and CV-events are patients undergoing repair of an
abdominal aortic aneurysm (AAA)[1,7]. The current prevalence of AAA for men above the
age of 65 ranges from 2% to 7% and elective treatment in the form of open (OAR) or
endovascular (EVAR) repair is advocated when the AAA-diameter reaches 5.5cm[8]. Both
OAR and EVAR can lead to significant insults to the kidney, such as hypovolaemia,
ischaemia-reperfusion injury, and contrast nephropathy[7,9]. EVAR is associated with better
short-term results compared to OAR; however this benefit is not sustained after the third
post-operative year [10-12]. We recently performed a cohort-study using the currently
acceptable AKI reporting-criteria and calculated the incidence of AKI after elective EVAR at
18.8% [1]. Further to AKI, patients with AAA have a significant burden of CV-morbidity
that may contribute to both post-operative decline in renal function and CV-events, regardless
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of the type of repair. Subsequently, this is a suitable population to assess a possible
association between AKI development and CV-events.
The primary aim of this study was to assess the impact of AKI on long-term CV-events after
aneurysm repair. A systematic review and meta-analysis of the literature were then performed
to confirm the impact of AKI on CV-events after similar types of intervention.
METHODS
Aneurysm repair cohort
Patients undergoing elective treatment for an infra-renal AAA [open (OAR) or endovascular
repair (EVAR)] between January 2004 and December 2012 in three tertiary referral centres
were included (Leicester Royal Infirmary, Leicester, UK; Department of Vascular Surgery,
Aristotle University, Greece; University Hospital Coventry and Warwickshire, Coventry,
UK). Patients were eligible for repair if they had an AAA diameter >5.5 cm or an AAA <5.5
cm with a sac increasing >1cm per year. EVAR was offered as first-line if repair was possible
using a device within instructions for use (IFU). Data were entered prospectively in an
electronic registry, once written informed consent had been obtained for the procedure and
data collection for the registry, following institutional ethical approval. Patients with
symptomatic, leaking, ruptured, infected, or inflammatory aneurysms or end-stage renal
disease (ESRD) receiving dialysis were excluded. All participants underwent a computed
tomographic angiography (CTA) to assess eligibility for EVAR. Blood samples at baseline
were obtained prior to imaging. Blood samples were also taken 24 and 48 hours after the
repair. For the EVAR patients, a standardized follow-up protocol, consisting of outpatient
clinic visits at 30 days, 6 months, 12 months after the operation, and annually thereafter, was
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employed. Imaging during follow-up included plain abdominal radiography and a CTA at 6
months, 12 months, and annually thereafter. This was the uniform standard follow-up
protocol for EVAR at the time in the included centres. Since 2012 patients undergo follow-up
guided by ultrasound imaging at the same intervals, with angiography reserved for suspected
endoleak[13-15]. OAR patients are followed-up at 30 days and 6 months without routine
cross-sectional imaging.
Aneurysm repair procedures
Endovascular repair
Commercially available endovascular devices were used (Table 1), with both infra- and
supra- renal fixation modalities. Indications and specifications have been described elsewhere
[16]. Procedures were performed in an operating theatre under general-anaesthesia using
fluoroscopic control and non-ionic contrast.
Open repair
Procedures were performed in an operating theatre under general-anaesthesia via a transperitoneal approach. A Dacron graft was used; supra-renal clamping was not applied in any
of the cases. Standard cardiac monitoring was available, including cardiac-output
measurement and central line monitoring. Patients remained in an intensive-care unit for at
least 24 hours.
Pre- and post-operative renal protection strategy
Prior to repair the administration of nephrotoxic contrast and non-steroidal anti-inflammatory
drugs were avoided (2 weeks). Metformin was discontinued for 2 days. For patients with a
pre-operative eGFR>60 ml/min/1.73m2, intravenous fluids (0.9% saline, 2mL/kg/hour) were
started on the day of the operation; those below that threshold were admitted one-day before
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and received intravenous fluids (0.9% saline, 1.5 L/24 hours) for 24 hours, until nil by mouth,
when they were commenced on 2mL/kg/hour. Urinary catheterization and hourly urineoutput measurements were routinely employed. Intra-operative fluid management was guided
by mean arterial-pressure (peripheral arterial line). Hartmann’s solution was used to keep the
mean arterial pressure within 80% of the baseline for 90% of the operating time. Hourly urine
output measurements continued until discharge. All patients received a statin and at least one
antiplatelet agent with aspirin being the first-choice (Table 1). All patients were asked to
mobilise and eat and drink as soon as possible. In case the patient developed AKI, they were
reviewed by a nephrologist. A blood transfusion was given if the patient’s haemoglobin was
< 8g/dl or if the patient had a history of cardiac-disease and was symptomatic with a
haemoglobin <10g/dl.
Definitions
Acute kidney injury (AKI) was defined as an increase in SCr >= 26.5 μmol/L, or >=50%
(1.5-fold from baseline), within 48 hours (the patient’s SCr measurements at 24 and 48 hours
were used) using the “Kidney-Disease Improving Global Outcomes” guideline (KDIGO)
definition [17]. Patients were then classified into 3 different stages of AKI. Stage 2 AKI was
defined as >2.0-2.9 times SCr rise and Stage 3 AKI was defined as >3.0 times SCr rise within
or rise to >354μmol/L or initiation of dialysis. Complications were defined according to the
reporting standards by Chaikof et al [18]. Hypercholesterolaemia was defined as total
cholesterol >5mmol/L [19] and hypertension as patient taking antihypertensive-medication or
blood pressure >=140/90mmHg[20]. Myocardial infarction was defined as a rise in Troponin
exceeding 5 times the 99th percentile of normal reference-range, when associated with new
ST-segment deviation, Q-waves or new left bundle branch block on an electrocardiogram, or
angiographically documented new graft or native coronary artery occlusion, or imaging
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evidence of new loss of viable myocardium [21]. Peripheral vascular-events were defined as
per the American Heart Association (AHA) [22]. Causes of death were coded based on the
patient’s death certificate. Cardiovascular death was defined as death immediately
attributable to a CV [23].
Systematic-review and meta-analysis
Subsequent to the cohort study, AS and MB performed a systematic electronic search
(Medline and Embase - April 2015) to identify studies assessing CV-events in populations
with AKI, using the following keywords: (“acute kidney injury” OR “acute renal failure” OR
“acute nephropathy” OR “AKI” OR “contrast induced nephropathy”) AND (“cardiovascular
event” OR “cardiac event” OR “myocardial infarction” OR “stroke” OR “heart failure”).
Overall, 2,542 abstracts were identified and screened by the authors (Supplementary Figure
1). Reference lists were also searched. Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA)[24] guidance was followed. Case-reports, case-series with <10
patients, and conference proceedings were excluded; all other types of publications were
deemed eligible for inclusion, given the lack of evidence from randomized controlled trials.
All publications identified were in English.
All studies represented retrospective
observational analyses of single or multicentre nature.
Endpoints
For the cohort study, a composite cardiovascular (CV) endpoint was used, which consisted
of: non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal peripheral vascular
events, hospitalisation due to heart failure, and death immediately due to a CV-event, as
defined above. For the meta-analysis, the primary endpoint was incidence of MI, as defined
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by each study, during follow-up as studies did not uniformly report incidence of stroke, heartfailure, or peripheral events that would enable calculation of a composite-endpoint.
Statistical analysis
For the cohort study, analyses were performed using the Statistical Package for Social
Sciences Version 21.0 (SPSS, Chicago, Ill, USA). Continuous parametric data are presented
as mean value ± standard deviation (SD) and categorical data are presented as absolute
values. Comparisons between study-groups were performed using the independent samples ttest for continuous parametric variables and Pearson’s chi-square test for categorical
variables. Cox-regression was used to assess the impact of AKI on CV-morbidity during
follow-up, together with factors where statistical comparison disclosed a p value <0.1
between groups with and without AKI (Table 1); age, sex, diabetes, history of previous MI or
stroke, use of statins, history of PAD, and hypertension were used in the multivariate
analyses, regardless of differences at baseline. A Bonferroni correction was applied. Metaanalysis was performed using the R suite for Windows. A random-effects model was used
due to the variability in baseline characteristics. Heterogeneity was assessed using the I2
statistic. Outcomes are reported as relative risks (RRs) with 95% Confidence Intervals (CIs).
The quality of randomized studies was assessed using the Newcastle–Ottawa Scale [25]. A pvalue level <0.05 was considered statistically significant.
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RESULTS
Aneurysm repair cohort
A total of 947 patients underwent EVAR and 121 patients underwent OAR. Baseline
characteristics of patients that did and did not develop AKI are summarized on Table 1. The
main parameter that differed at baseline (univariate analysis) was eGFR (calculated using the
CKD-EPI formula)[26] as documented on Table 1. Overall, a total of 167 patients (18%)
undergoing EVAR and a total of 21 patients (17%) undergoing OAR developed AKI;
incidence was similar among the 3 centres (for EVAR: 16.4% vs 18.2% vs 17.8% - for OAR:
16% vs 17% vs 17%). Of these, 12 (1.3%) EVAR patients developed stage-2 and 2 (0.2%)
EVAR patients developed stage-3 AKI; 4 (3%) OAR patients developed stage-2 and 4 (3%)
stage-3 AKI. All others developed stage-1 AKI. None required dialysis during the immediate
post-operative period (30 days) and none of the OAR patients developed AKI past the 48
hour definition point used in the study.
During a median follow-up of 61 (range: 34-110) months for EVAR and 66 months (range:
11-121) for OAR, 11.8% of EVAR and 8.3% of OAR patients died; 36.1% of EVAR and
32.3% of OAR patients developed CV-events (Table 2). On univariate analysis, development
of AKI in both the EVAR and the OAR groups was associated with long-term CV-events as
per the endpoint at completion of follow-up [EVAR: Risk Ratio (RR) 1.52, 95% Confidence
Interval (CI) 1.23-1.82, p<0.001; OAR: RR 2.12, 95% CI: 1.30-2.46, p=0.01]. Kaplan-Meier
analysis showed that patients who did develop AKI in the EVAR (p=0.01) and OAR (p=0.02)
groups were more likely to then develop CV-events (Figure 1). Adjusted analyses in the
EVAR (947 patients included in the model; adjusted for: age, sex, diabetes, previous MI,
previous stroke, hypertension, history of PAD, smoking-habit, baseline eGFR, use of statin
and beta-blocker, history of COPD) and the combined population (EVAR and OAR, 1,068
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patients included in the model) disclosed that AKI was independently associated with CVevents [EVAR: Hazard Ratio (HR) 1.76, 95% CI 1.06-2.92, p=0.03; combined EVAR and
OAR: HR 1.73, 95% CI 1.06-2.83, p=0.03] (Supplementary Tables 1 and 2).
Meta-analysis
The systematic review identified 21 manuscripts [27-44] reporting CV-events after
development of AKI, beyond the first 30-days after AKI development (Tables 3 and 4;
supplementary Figures 1 to 4; supplementary Table 3). All were retrospective-studies and the
majority reported on patients undergoing percutaneous coronary intervention (PCI). One
study reported on CV-events after hospitalization in an intensive care unit and 5 studies
reported on CV-events after coronary artery bypass grafting (CABG). One study (not
included in the meta-analysis) provided data on major adverse cardiac events after aortic
surgery for type-A dissection[45]. Also, one study (not included in the meta-analysis)
reported CV-events after admission in intensive care (regardless of the underlying diagnosis)
and development of AKI. Our meta-analysis focused on the populations undergoing PCI and
CABG. Reporting of incidence of stroke, heart failure and other cardiac events varied
significantly and adjusted analyses were performed in only 8 studies, using different variables
for adjustment in each case, hence meta-analysis of adjusted Hazard Ratios (HRs) was not
undertaken. Additionally, incidence of CV-events was reported at different points in time,
with most papers reporting CV-morbidity at 1 year. Hence, for studies including patients
undergoing PCI, we performed meta-analysis of data at: 1 year, when 7 studies [27,28,3033,39] reported incidence of myocardial-infarction (MI) on 23,936 patients with a pooled
risk-ratio (RR) of 1.76 (95%CI: 1.45-2.12, p<0.001, I2= 50.6%); 2 years, when 3 studies
[34,41,44] reported incidence of MI on 17,773 patients with a pooled RR of 1.34 (95%CI:
1.10-1.63, p=0.003, I2= 33.9%). Results after the 2nd year for PCI studies were not reported in
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a uniform manner and significant heterogeneity did not allow further pooled calculations. For
patients undergoing cardiac surgery, CV-events were reported at 5 years. More specifically, 3
studies [37,42,43] reported incidence of MI following major cardiac surgery on 33,701
patients with a pooled RR of 1.60 (95%CI: 1.43-1.81, I2=0%). In addition to these, one
retrospective study of 375 patients undergoing open aortic reconstruction for type-A
dissection showed that AKI stage 3 as per the KDIGO criteria is associated with major
cardiac adverse events at a median follow-up of 2.6 years, with an adjusted HR of 5.55 (95%
CI: 2.13-14.43). Data for the overall AKI population (all stages) were not reported and data
regarding MI, stroke, HF and/or other vascular events were not separately reported, thereby
not allowing inclusion in the meta-analysis model[45]. Regarding publication bias, a Funnel
plot analysis was performed; for the PCI studies reporting MI incidence, Egger’s test was
significant (p=0.01) at 1 year and not significant (p=0.93) at 2 years. For the studies reporting
outcomes after cardiac surgery at 5 years, Egger’s test was significant (p=0.01). However, for
the studies where Egger’s test was significant, the overall effect size did not change
significantly when separate studies were sequentially removed from the analysis.
DISCUSSION
This study suggests that development of AKI after intervention in populations at high-risk for
CV-morbidity is associated with CV-events at long-term. We chose to primarily investigate
CV-events in patients undergoing endovascular (EVAR) or open (OAR) aneurysm repair, as
they have a high-prevalence of AKI risk-factors. Despite that, their eGFR was still fairly well
preserved in our series. Still, prevalence of diabetes and baseline renal-dysfunction were
more common in our AKI group (compared to those without AKI). In our EVAR cohort,
development of AKI was associated with CV-events both at univariate and adjusted analyses.
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To confirm this association, we interrogated the literature in a systematic review. Metaanalysis (for incidence of MI) was possible for patients undergoing percutaneous coronary
intervention at 1 year and patients undergoing coronary artery bypass grafting at 5 years. The
findings in the meta-analysis re-iterate our initial findings.
AKI is a sudden, usually reversible, deterioration of renal function that has been associated
with increased mortality, morbidity, and healthcare-cost [46]. A study involving 10,518
patients undergoing surgery suggested that long-term survival was worse among patients with
AKI, even those with complete recovery of renal-function [47]. In a large meta-analysis
development of AKI impacted on long-term mortality with a pooled-adjusted HR of 2.0 (95%
CI: 1.3-3.1) [6].
Long-term CV-events in populations with AKI have not been investigated to the same extent.
We attempted to assess this association in patients undergoing AAA-repair as they have a
significant burden of CV-morbidity and AKI risk-factors. They also typically suffer several
CV-events after repair: in the EVAR randomized-trials (OAR versus EVAR) the incidence
of major CV-events at 5 years was 35% [48]. Patients undergoing AAA repair are also likely
to develop AKI due to a variety of reasons. Among these undergoing OAR the renal injury is
mostly due to hypovolaemia, ischaemia-reperfusion injury and aortic cross-clamping[7] with
an incidence between 10-20%. EVAR represents a minimally invasive alternative; however,
AKI is still common due to: intra-arterial nephrotoxic contrast administration, renalmicroembolisation, dissection or coverage of renal arteries, lower-limb ischaemia and
ischaemia-reperfusion syndrome, hypovolaemia, and CV-disease[7]. Using the
KDIGO
criteria, we recently documented an incidence of 18% after elective EVAR [1]. Given the
high-incidence of AKI and CV-events in this population we considered it ideal in order to
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investigate a possible association between the two. Similar to previous studies, the incidence
of CV-morbidity in our AAA-cohort was 35.6% over 5-years. Unfortunately, the randomized
EVAR studies have not reported AKI-incidence. Additionally, the majority of observational
EVAR-studies have used inconsistent reporting criteria for AKI [7,12]. A recent study
retrospectively reported on 375 individuals undergoing reconstruction for type-A dissection
showing that AKI stage 3 is associated with cardiac adverse events at a follow-up of 2.6
years[45]. Our data confirms this association; however, our population and analyses are
different in many respects. Open surgery for type-A dissection is more invasive and AKI is
therefore more common compared to AAA-intervention. Also, type-A dissection is a rare
pathology compared to AAA. Further to this, we haven’t focused exclusively on stage-3 AKI
but included all patients in our analyses. As a result, findings from out cohort are more
generalizable.
Whether AKI is the precipitating factor behind CV-events or these patients are simply more
likely to have a more significant burden of occult CV-morbidity remains unclear. Based on
our findings we may regard development of AKI as a marker of higher CV-risk. It is unclear
how and if AKI pathogenically accelerates CV-morbidity. To answer this, further
mechanistic evidence is necessary. If we consider AKI as a marker indicating worse CVoutcome, we need to offer this population more aggressive follow-up and CV-prevention.
AKI prevention may also be pivotal. Unfortunately, to the authors’ knowledge, the various
AKI prevention trials, mostly in cardiac intervention, do not offer sufficient long-term
follow-up in terms of CV-events to assess the exact role of AKI prevention on long-term
events.
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Regarding AKI-prevention in AAA repair, hydration is traditionally considered as the
mainstay of prevention [7]. This is because volume expansion protects the tubule from
ischaemic and oxidative insults. However, given the multifactorial nature of renal-injury,
simple hydration may not be sufficient. We previously performed a systematic-review, which
identified a paucity of randomized evidence investigating reno-protection these patients [7].
This study has certain limitations that need to be mentioned. Firstly, it represents a
retrospective analysis, even though based on prospectively maintained datasets, and
limitations such as coding errors are unavoidable. The study is also limited by loss to followup, as is the case in all observational reports. Patients at baseline did not have available data
regarding proteinuria or subclinical markers of kidney injury and we have not collected data
on renal artery stenoses, which may impact on AKI development. Regarding the doseresponse relationship between severity of AKI and subsequent CV outcomes, only a small
number of patients in this series developed stage 2 or 3 AKI, hence such an association is
difficult to examine using our data due to type-2 error. In the systematic review, all studies
are retrospective and non-uniform definitions of CV-events during follow-up did not allow a
calculation. The definitions used for AKI are also not completely identical; however, they
have all used universally accepted criteria to report incidence.
Overall, this study suggests that AKI is associated with long-term CV-events in populations
at high-risk after intervention. Relevant reno-protective strategies, both in the short and long
term should be investigated.
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REFERENCES
1
Saratzis A, Melas N, Mahmood A, Sarafidis P: Incidence of acute kidney injury (aki) after
endovascular abdominal aortic aneurysm repair (evar) and impact on outcome. Eur J Vasc Endovasc
Surg 2015
2
Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW: Acute kidney injury, mortality,
length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365-3370.
3
McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J: Epidemiology
and prognostic implications of contrast-induced nephropathy. Am J Cardiol 2006;98:5K-13K.
4
Li SY, Chen JY, Yang WC, Chuang CL: Acute kidney injury network classification predicts inhospital and long-term mortality in patients undergoing elective coronary artery bypass grafting
surgery. Eur J Cardiothorac Surg 2011;39:323-328.
5
Kerr M, Bedford M, Matthews B, O'Donoghue D: The economic impact of acute kidney injury
in england. Nephrol Dial Transplant 2014;29:1362-1368.
6
Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: A
systematic review and meta-analysis. Kidney Int 2012;81:442-448.
7
Saratzis AN, Goodyear S, Sur H, Saedon M, Imray C, Mahmood A: Acute kidney injury after
endovascular repair of abdominal aortic aneurysm. J Endovasc Ther 2013;20:315-330.
8
Cosford PA, Leng GC: Screening for abdominal aortic aneurysm. Cochrane Database Syst Rev
2007:CD002945.
9
Saratzis A, Sarafidis P, Melas N, Khaira H: Comparison of the impact of open and
endovascular abdominal aortic aneurysm repair on renal function. J Vasc Surg 2014
10
De Bruin JL, Baas AF, Buth J, Prinssen M, Verhoeven EL, Cuypers PW, van Sambeek MR, Balm
R, Grobbee DE, Blankensteijn JD: Long-term outcome of open or endovascular repair of abdominal
aortic aneurysm. N Engl J Med 2010;362:1881-1889.
11
Lederle FA, Freischlag JA, Kyriakides TC, Matsumura JS, Padberg FT, Jr., Kohler TR, Kougias P,
Jean-Claude JM, Cikrit DF, Swanson KM, Group OVACS: Long-term comparison of endovascular and
open repair of abdominal aortic aneurysm. N Engl J Med 2012;367:1988-1997.
12
Stather PW, Sidloff D, Dattani N, Choke E, Bown MJ, Sayers RD: Systematic review and metaanalysis of the early and late outcomes of open and endovascular repair of abdominal aortic
aneurysm. Br J Surg 2013;100:863-872.
13
Beeman BR, Doctor LM, Doerr K, McAfee-Bennett S, Dougherty MJ, Calligaro KD: Duplex
ultrasound imaging alone is sufficient for midterm endovascular aneurysm repair surveillance: A cost
analysis study and prospective comparison with computed tomography scan. J Vasc Surg
2009;50:1019-1024.
14
Chaer RA, Gushchin A, Rhee R, Marone L, Cho JS, Leers S, Makaroun MS: Duplex ultrasound
as the sole long-term surveillance method post-endovascular aneurysm repair: A safe alternative for
stable aneurysms. J Vasc Surg 2009;49:845-849; discussion 849-850.
15
Bakken AM, Illig KA: Long-term follow-up after endovascular aneurysm repair: Is ultrasound
alone enough? Perspect Vasc Surg Endovasc Ther 2010;22:145-151.
16
Saratzis N, Melas N, Saratzis A, Lazarides J, Ktenidis K, Tsakiliotis S, Kiskinis D: Anaconda
aortic stent-graft: Single-center experience of a new commercially available device for abdominal
aortic aneurysms. J Endovasc Ther 2008;15:33-41.
17
Summary of recommendation statements. Kidney international supplements 2012;2:8-12.
18
Chaikof EL, Blankensteijn JD, Harris PL, White GH, Zarins CK, Bernhard VM, Matsumura JS,
May J, Veith FJ, Fillinger MF, Rutherford RB, Kent KC: Reporting standards for endovascular aortic
aneurysm repair. J Vasc Surg 2002;35:1048-1060.
19
Mannu GS, Zaman MJ, Gupta A, Rehman HU, Myint PK: Update on guidelines for
management of hypercholesterolemia. Expert Rev Cardiovasc Ther 2012;10:1239-1249.
20
Ritchie LD, Campbell NC, Murchie P: New nice guidelines for hypertension. BMJ
2011;343:d5644.
16
21
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Joint
ESCAAHAWHFTFftUDoMI, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H,
Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm
CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM,
Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G,
Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL,
Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S: Third
universal definition of myocardial infarction. Circulation 2012;126:2020-2035.
22
Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss LK, Golzarian J, Gornik HL,
Halperin JL, Jaff MR, Moneta GL, Olin JW, Stanley JC, White CJ, White JV, Zierler RE, American College
of Cardiology Foundation/American Heart Association Task Force on Practice G, Society for
Cardiovascular A, Interventions, Society of Interventional R, Society for Vascular M, Society for
Vascular S: 2011 accf/aha focused update of the guideline for the management of patients with
peripheral artery disease (updating the 2005 guideline): A report of the american college of
cardiology foundation/american heart association task force on practice guidelines: Developed in
collaboration with the society for cardiovascular angiography and interventions, society of
interventional radiology, society for vascular medicine, and society for vascular surgery. J Vasc Surg
2011;54:e32-58.
23
Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff
MR, Lichtman JH, Limacher MC, Mahaffey KW, Mehran R, Nissen SE, Smith EE, Targum SL: 2014
acc/aha key data elements and definitions for cardiovascular endpoint events in clinical trials: A
report of the american college of cardiology/american heart association task force on clinical data
standards (writing committee to develop cardiovascular endpoints data standards). J Am Coll Cardiol
2014
24
PRISMA: Prisma statement, 2009, 2009,
25
Egger M, Smith GD: Bias in location and selection of studies. BMJ 1998;316:61-66.
26
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P,
Van Lente F, Greene T, Coresh J: A new equation to estimate glomerular filtration rate. Ann Intern
Med 2009;150:604-612.
27
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW,
Mathew V, Garratt KN, Holmes DR, Jr.: Incidence and prognostic importance of acute renal failure
after percutaneous coronary intervention. Circulation 2002;105:2259-2264.
28
Lindsay J, Apple S, Pinnow EE, Gevorkian N, Gruberg L, Satler LF, Pichard AD, Kent KM,
Suddath W, Waksman R: Percutaneous coronary intervention-associated nephropathy foreshadows
increased risk of late adverse events in patients with normal baseline serum creatinine. Catheter
Cardiovasc Interv 2003;59:338-343.
29
Bartholomew BA, Harjai KJ, Dukkipati S, Boura JA, Yerkey MW, Glazier S, Grines CL, O'Neill
WW: Impact of nephropathy after percutaneous coronary intervention and a method for risk
stratification. Am J Cardiol 2004;93:1515-1519.
30
Dangas G, Iakovou I, Nikolsky E, Aymong ED, Mintz GS, Kipshidze NN, Lansky AJ, Moussa I,
Stone GW, Moses JW, Leon MB, Mehran R: Contrast-induced nephropathy after percutaneous
coronary interventions in relation to chronic kidney disease and hemodynamic variables. Am J
Cardiol 2005;95:13-19.
31
Bouzas-Mosquera A, Vazquez-Rodriguez JM, Calvino-Santos R, Peteiro-Vazquez J, Flores-Rios
X, Marzoa-Rivas R, Pinon-Esteban P, Aldama-Lopez G, Salgado-Fernandez J, Vazquez-Gonzalez N,
Castro-Beiras A: [contrast-induced nephropathy and acute renal failure following emergent cardiac
catheterization: Incidence, risk factors and prognosis]. Revista espanola de cardiologia
2007;60:1026-1034.
32
Harjai KJ, Raizada A, Shenoy C, Sattur S, Orshaw P, Yaeger K, Boura J, Aboufares A, Sporn D,
Stapleton D: A comparison of contemporary definitions of contrast nephropathy in patients
17
undergoing percutaneous coronary intervention and a proposal for a novel nephropathy grading
system. Am J Cardiol 2008;101:812-819.
33
Cho JY, Jeong MH, Hwan Park S, Kim IS, Park KH, Sim DS, Yoon NS, Yoon HJ, Park HW, Hong
YJ, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC: Effect of contrast-induced nephropathy on cardiac
outcomes after use of nonionic isosmolar contrast media during coronary procedure. Journal of
cardiology 2010;56:300-306.
34
James MT, Ghali WA, Knudtson ML, Ravani P, Tonelli M, Faris P, Pannu N, Manns BJ,
Klarenbach SW, Hemmelgarn BR, Alberta Provincial Project for Outcome Assessment in Coronary
Heart Disease I: Associations between acute kidney injury and cardiovascular and renal outcomes
after coronary angiography. Circulation 2011;123:409-416.
35
Olsson D, Sartipy U, Braunschweig F, Holzmann MJ: Acute kidney injury following coronary
artery bypass surgery and long-term risk of heart failure. Circulation Heart failure 2013;6:83-90.
36
Gammelager H, Christiansen CF, Johansen MB, Tonnesen E, Jespersen B, Sorensen HT:
Three-year risk of cardiovascular disease among intensive care patients with acute kidney injury: A
population-based cohort study. Crit Care 2014;18:492.
37
Ryden L, Ahnve S, Bell M, Hammar N, Ivert T, Sartipy U, Holzmann MJ: Acute kidney injury
after coronary artery bypass grafting and long-term risk of myocardial infarction and death. Int J
Cardiol 2014;172:190-195.
38
Holzmann MJ, Ryden L, Sartipy U: Acute kidney injury and long-term risk of stroke after
coronary artery bypass surgery. Int J Cardiol 2013;168:5405-5410.
39
Watabe H, Sato A, Hoshi T, Takeyasu N, Abe D, Akiyama D, Kakefuda Y, Nishina H, Noguchi Y,
Aonuma K: Association of contrast-induced acute kidney injury with long-term cardiovascular events
in acute coronary syndrome patients with chronic kidney disease undergoing emergent
percutaneous coronary intervention. Int J Cardiol 2014;174:57-63.
40
Kume K, Yasuoka Y, Adachi H, Noda Y, Hattori S, Araki R, Kohama Y, Imanaka T, Matsutera R,
Kosugi M, Sasaki T: Impact of contrast-induced acute kidney injury on outcomes in patients with stsegment elevation myocardial infarction undergoing primary percutaneous coronary intervention.
Cardiovascular revascularization medicine : including molecular interventions 2013;14:253-257.
41
Hernando L, Canovas E, Freites A, de la Rosa A, Alonso J, Del Castillo R, Salinas P, Montalvo
GB, Huelmos AI, Botas J: Prevalence and prognosis of percutaneous coronary interventionassociated nephropathy in patients with acute coronary syndrome and normal kidney function.
Revista espanola de cardiologia 2015;68:310-316.
42
Hansen MK, Gammelager H, Jacobsen CJ, Hjortdal VE, Layton JB, Rasmussen BS, Andreasen
JJ, Johnsen SP, Christiansen CF: Acute kidney injury and long-term risk of cardiovascular events after
cardiac surgery: A population-based cohort study. Journal of cardiothoracic and vascular anesthesia
2015
43
Hansen MK, Gammelager H, Mikkelsen MM, Hjortdal VE, Layton JB, Johnsen SP, Christiansen
CF: Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke
among elective cardiac surgical patients: A cohort study. Crit Care 2013;17:R292.
44
Huseyin Uyarel NC, Mehmet Ergelen, Emre Akkaya, Erkan Ayhan, Turgay Isik, Gokhan Cicek,
Zeki Yuksel Gunaydin, Damirbek Osmonov, Mehmet Gul, Deniz Demirci, Mehmet Rasit Guney, Recep
Ozturk, Ibrahim Yekeler: Contrast-induced nephropathy in patients undergoing primary angioplasty
for acute myocardial infarction: Incidence, a simple risk score, and prognosis. Archives of Medical
Science 2009;5:550-558.
45
Ko T, Higashitani M, Sato A, Uemura Y, Norimatsu T, Mahara K, Takamisawa I, Seki A,
Shimizu J, Tobaru T, Aramoto H, Iguchi N, Fukui T, Watanabe M, Nagayama M, Takayama M,
Takanashi S, Sumiyoshi T, Komuro I, Tomoike H: Impact of acute kidney injury on early to long-term
outcomes in patients who underwent surgery for type a acute aortic dissection. Am J Cardiol 2015
46
Hawkes N: Acute kidney injury is a more important safety issue than mrsa, says nice. BMJ
2013;347:f5302.
18
47
Bihorac A, Yavas S, Subbiah S, Hobson CE, Schold JD, Gabrielli A, Layon AJ, Segal MS: Longterm risk of mortality and acute kidney injury during hospitalization after major surgery. Ann Surg
2009;249:851-858.
48
Brown LC, Thompson SG, Greenhalgh RM, Powell JT: Incidence of cardiovascular events and
death after open or endovascular repair of abdominal aortic aneurysm in the randomized evar trial
1. Br J Surg 2011;98:935-942.
Table headings
Table 1: Baseline characteristics for the study groups
Table 2: Events for the study groups during follow-up
Table 3: Characteristics of studies reporting long-term cardiovascular events after acute
kidney injury (AKI)
Table 4: Events during follow-up in studies reporting cardiovascular outcome after
development of acute kidney injury (AKI)
Figure legends
Figure 1: Kaplan Meier analysis of cardiovascular events during follow-up for patients
undergoing open or endovascular abdominal aortic aneurysm repair.