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Chin Med J 2014;127 (12) 2332

DOI: 10.3760/cma.j.issn.0366-6999.20133154
Department of Cardiology, Shenyang Northern Hospital, Shenyang,
Liaoning 110016, China (Li J, Li Y, Wang XZ, Jing QM, Ma YY,
Wang ZL, Liang YC and Han YL)
Department of Cardiology, Jinan Military 88th Hospital, Taian,
Shandong 271000, China (Yang SG)
Department of Cardiology, Henan Provincial Peoples Hospital,
Zhengzhou, Henan 450003, China (Gao CY)
Department of Cardiology, First Affiliated Hospital of Lanzhou
University, Lanzhou, Gansu 730000, China (Zhang Z)
Department of Cardiology, Daping Hospital and the Research
Institute of Surgery of the Third Military Medical University,
Chongqing 400038, China (Yang CM)
Department of Cardiology, The 306th Hospital of Peoples Liberation
Army, Beijing 10000, China (Wang SL)
Correspondence to: Dr. Han Yaling, Department of Cardiology,
Shenyang Northern Hospital, Shenyang, Liaoning 110016, China
(Tel: 86-24-28851168. Fax: 86-24-28851120. Email: hanyaling@263.
This work was supported by grants from the Key technologies
R&D project of Liaoning Province (No. 2013225089) and Key
Project of National 12th Five-Year Research Program of China (No.
Original article
Age, estimated glomerular fltration rate and ejection fraction score
predicts contrast-induced acute kidney injury in patients with
diabetes and chronic kidney disease: insight from the TRACK-D
Li Jing, Li Yi, Wang Xiaozeng, Yang Shuguang, Gao Chuanyu, Zhang Zheng, Yang Chengming, Jing Quanming,
Wang Shouli, Ma Yingyan, Wang Zulu, Liang Yanchun and Han Yaling
Keywords: AGEF score; contrast induced acute kidney injury; diabetes; chronic kidney disease
Background The occurrence of contrast induced acute kidney injury (CIAKI) has a pronounced impact on morbidity and
mortality. The aim of the present study was to appraise the diagnostic effcacy of age, estimated glomerular fltration rate
(eGFR) and ejection fraction (AGEF) score (age/EF(%)+1 (if eGFR was <60 mlmin
1.73 m
)) as an predictor of CIAKI in
patients with diabetes mellitus (DM) and concomitant chronic kidney disease (CKD).
Methods The AGEF score was calculated for 2 998 patients with type 2 DM and concomitant CKD who had undergone
coronary/peripheral arterial angiography. CIAKI was defined as an increase in sCr concentration of 0.5 mg/dl (44.2
mmol/L) or 25% above baseline at 72 hours after exposure to the contrast medium. Post hoc analysis was performed by
stratifying the rate of CIAKI according to AGEF score tertiles. The diagnostic effcacy of the AGEF score for predicting
CIAKI was evaluated with receiver operating characteristic (ROC) analysis.
Results The AGEF score ranged from 0.49 to 3.09. The AGEF score tertiles were defned as follows: AGEF
(n=1 006); 0.92 <AGEF
1.16 (n=1 000), and ACEF
>1.16 (n=992). The incidence of CIAKI was signifcantly different
in patients with low, middle and high AGEF scores

=1.1%, AGEF
=2.3% and AGEF
=5.8%, P <0.001). By
multivariate analysis, AGEF score was an independent predictor of CIAKI (odds ratio=4.96, 95% CI: 2.3210.58, P <0.01).
ROC analysis showed that the area under the curve was 0.70 (95% CI: 0.6480.753, P <0.001).
Conclusion The AGEF score is effective for stratifying risk of CIAKI in patients with DM and CKD undergoing coronary/
peripheral arterial angiography. (Clinical Trial identifer: NCT00786136).
Chin Med J 2014;127 (12): 2332-2336
ontrast-induced acute kidney injury (CIAKI) is a major
complication with significantly increased mortality
and morbidity after iodinated contrast media administration
compared to non-CIAKI patients.
Although the
occurrence of CIAKI is numerically low in patients with
normal renal function, it is higher in patients with diabetes
mellitus (DM), especially those with concomitant chronic
kidney disease (CKD).
So the early identification of
CIAKI in this high risk patient population is crucial.
Several predictive algorithms have been proposed to
estimate the risk of CIAKI in patients undergoing invasive
coronary diagnosis and/or intervention.
The age,
estimated glomerular filtration rate (eGFR) and ejection
fraction (AGEF) score is one of the established risk
predicting models based on the principle of parsimony.
It has proven effective in predicting CIAKI and major
ischemic events in patients undergoing percutaneous
coronary intervention (PCI).
However, the value of AGEF
score in high risk patients has not been elucidated. The
aim of this study was to evaluate the diagnostic effcacy of
AGEF score in predicting the risk of CIAKI in DM patients
with mild-to-moderate CKD after coronary/peripheral
arterial angiography.
Study population
Patients included in this study were from the Short-
Term Rosuvastatin Therapy for Prevention of Contrast-
Chinese Medical Journal 2014;127 (12) 2333
Induced Acute Kidney Injury in Patients with Diabetes and
Chronic Kidney Disease (TRACK-D) study.
was an investigator-initiated, prospective, randomized,
multicenter trial performed in China (clinical trial identifer:
NCT00786136). A total of 2 998 patients were enrolled in
53 medical centers. The inclusion criteria were age 18 to
75 years old, with type 2 DM and concomitant CKD, with
planned coronary/peripheral arterial diagnostic angiography,
left ventriculography or PCI. Exclusion criteria were
hypersensitivity to contrast medium or statins, type 1 DM,
ketoacidosis, lactic acidosis, stage 0 or 1 CKD, stage 4 or
5 CKD, acute ST-segment elevation myocardial infarction
(STEMI) within the previous four weeks, class IV heart
failure as defined by the New York Heart Association
(NYHA) functional classification system, hemodynamic
instability, administration of iodinated contrast medium
during the two weeks before randomization, low-density
lipoprotein cholesterol (LDL-C) concentration <1.82 mmol/L,
hepatic dysfunction (serum alanine-aminotransferase
(ALT) concentration three times greater than the
upper limit of normal), thyroid insufficiency, or renal
artery stenosis (unilateral >70% or bilateral >50%).
The eGFR was calculated from serum creatinine
(sCr) concentrations using the modified glomerular
filtration rate estimating equation for Chinese patients
with CKD
: eGFR (mlmin
1.73 m
(0.79 if patient is female). The AGEF score
was calculated as described in a previous study:
EF(%)+1 (if eGFR was <60 mlmin
1.73 m
Study protocol
All patients provided written informed consent before
enrollment. Hydration therapy was standard and
administered at the physicians discretion and included
isotonic saline (0.9% sodium chloride, 1 mlmin
1.73 m
started 12 hours before and continued for 24 hours after
contrast medium administration. After enrollment, patients
were randomized to either rosuvastatin (Crestor
AstraZeneca, UK) 10 mg every evening from two days
before to three days after contrast medium administration
(total dose of 50 mg rosuvastatin over fve days) or control
group. Patients assigned to the control group did not receive
any statins. Statin therapy was resumed in both groups
three days after contrast media administration, following
completion of the study endpoints. The iso-osmolar,
nonionic contrast medium iodixanol (320 mg iodine/ml;
Visipaque; GE Healthcare) was administered during all
procedures. Wall motion abnormalities and left ventricular
ejection fraction (EF) were rapidly assessed with
echocardiography in all subjects. Blood samples were taken
to measure sCr concentrations before randomization and at
48 and 72 hours after contrast medium administration. The
peak post-procedural sCr value was used for the primary
end point evaluation. Renal function was measured using
eGFR in all patients. Type 2 DM was diagnosed using the
criteria of the American Diabetes Association.
of high-sensitivity C-reactive protein (hsCRP), total
cholesterol (TC), and low-density lipoprotein cholesterol
(LDL-C) were also measured using commercial kits on the
day of admission and three days after the procedure.
Endpoints and defnitions
The primary end point was the development of CIAKI,
defned as an increase in sCr concentration 0.5 mg/dl (44.2
mmol/L) or 25% above baseline at 72 hours after exposure
to the contrast medium. Clinical outcomes included events
occurring within 30 days after contrast: (1) all-cause
death; (2) dialysis or hemofiltration due to symptoms or
signs of uremic syndrome or management of refractory
hypervolemia, hyperkalemia, or acidosis;
or (3) worsening
heart failure, defined as a deteriorated NYHA functional
class (class change 1). All patients had a follow-up
evaluation at a clinic visit or via telephone contact at 30
days. The China Cardiovascular Research Foundation
(CCRF), an independent clinical research organization, was
responsible for database management, safety monitoring,
and adverse event evaluation. All adverse events were
adjudicated by a blinded, independent clinical events
committee. The CCRF reviewed the data periodically to
identify any potential safety issues.
Statistical analysis
Statistical analysis was based on the modifed intention-to-
treat populations and performed using SAS version 9.13
software (SAS Institute Inc., Cary, NY, USA). Comparisons
among normally distributed continuous variables, expressed
as meanstandard deviation (SD), were performed using
t tests; non-normally distributed continuous variables,
presented as medians and interquartile ranges, were
analyzed using Wilcoxon rank sum tests. The chi-square or
Fisher exact test were used for categorical data, expressed
as percentages. A multivariate analysis was performed to
identify the independent predictors of CIAKI by binary
Logistic regression model. All the available variables
considered potentially relevant included AGEF score, male,
age, diabetes history, body mass index, acute coronary
syndromes, eGFR, ejection fraction, hemoglobin, hydration
and adjunctive medications (rosuvastatin, ACEI/ARB and
Beta-blocker). A receiver operating characteristic (ROC)
curve was used to evaluate the diagnostic efficacy of the
AGEF score in predicting CIAKI. All P values were two-
tailed, and statistical signifcance was defned by a P value
Baseline characteristics and AGEF score distribution
Demographic characteristics and procedural data are
summarized in Table 1. Of the 2 998 patients, 85.9%
underwent diagnostic coronary angiography and left
ventriculography (n=2 575), 13.5% diagnostic coronary/
peripheral angiography and left ventriculography (n=405),
0.6% peripheral angiography (n=18), 53.0% PCI (n=1 589),
and 1.0% percutaneous peripheral intervention (n=30). The
mean procedural contrast volume was (16463) ml.
The AGEF score ranged from 0.49 to 3.09, with meanSD
of 1.160.45 and a median of 1.03. We defned the AGEF
Chin Med J 2014;127 (12) 2334
score tertiles as follows: AGEF
0.92 (n=1 006), 0.92
1.16 (n=1 000) and ACEF
>1.16 (n=992).
The baseline clinical and procedure characteristics were
quite different among the different tertiles as shown in
Table 1. In brief, patients with higher AGEF scores were
more likely female, elder, with lower body mass index, had
higher proportion in hypertension, heart failure, and prior
myocardial infarction, received more diuretic drugs and less
hydration treatment. Laboratory tests showed that patients
with high AGEF scores had significantly higher baseline
serum creatinine concentrations.
Prediction of CIAKI and clinical events
The incidences of CIAKI and clinical events corresponding
to different tertiles are shown in Table 2. An signifcantly
increasing increment of the CIAKI occurrence from
low to high tertiles was observed (AGEF
=2.3%, AGEF
=5.8%, P <0.001). Moreover, the
increase of AGEF score was also associated with increased
incidences of all cause death (AGEF
=0, AGEF
=0.7%, P =0.004) and worsening heart failure
=2. 3%, AGEF
=3. 6%, AGEF
=4. 4%,
P=0.029). The incidence of dialysis or hemofltration was
similar among different tertiles.
Multivariate analysis results
By multivariate analysis, the increment of AGEF score
was a strong independent predictor of CIAKI (odds ratio
(OR)=4.96, 95% CI: 2.3210.58, P <0.01) (Table 3). Other
independent predictors included ejection fraction (OR=0.88,
95% CI: 0.850.91), use of rosuvastatin (OR=0.54, 95%
CI: 0.330.88), eGFR <60 mlmin
1.73 m
95% CI: 1.031.06) and hemoglobin (OR=0.98, 95% CI:
ROC analysis
ROC analysis showed that the area under the curve was
0.70 (95% CI: 0.6480.753, P <0.001, Figure 1), which
indicates an acceptable, moderate diagnostic efficacy of
AGEF score for CIAKI prediction in patients with DM and
Table 1. Baseline characteristics according to AGEF tertiles
Characteristics AGEF
(n=1 006) AGEF
(n=1 000) AGEF
(n=992) P values
Male (n (%)) 733 (72.9) 611 (61.1) 610 (61.5) <0.001
Age (years) 53.906.73 62.895.87 67.636.84 <0.001
Body mass index 25.802.81 25.572.99 25.303.08 0.01
Hypertension (n (%)) 658 (65.4) 723 (72.3) 775 (78.1) <0.001
Congestive heart failure (n (%)) 153 (15.2) 126 (12.6) 186 (18.8) 0.001
Peripheral vascular disease (n (%)) 21 (2.1) 20 (2.0) 41 (4.1) 0.004
Prior myocardial infarction (n (%)) 179 (17.8) 194 (19.4) 245 (24.7) <0.001
Procedural results (n (%))
Peripheral angiography 88 (8.7) 139 (13.9) 199 (20.1) <0.001
Coronary angiography 995 (99.6) 994 (99.5) 991 (99.1) 0.310
Normal coronary 165 (16.4) 103 (10.3) 107 (10.8) <0.001
Single vessel intervention 310 (30.8) 217 (21.7) 168 (16.9) <0.001
Multivessel intervention 531 (52.8) 680 (68.0) 717 (72.3) <0.001
Medications (n (%))
Aspirin 963 (95.7) 928 (92.8) 925 (93.2) 0.013
ACEI 690 (68.6) 645 (64.5) 593 (59.8) <0.001
ARB 181 (18.0) 244 (24.4) 291 (29.3) <0.001
Beta-blocker 857 (85.2) 786 (78.6) 782 (78.8) <0.001
Statin 506 (50.3) 497 (49.7) 497 (50.1) 0.963
Diuretic 139 (13.8) 202 (20.2) 309 (31.1) <0.001
Calcium antagonist 364 (36.2) 427 (42.7) 447 (45.1) <0.001
Heparin 629 (62.5) 631 (63.1) 607 (61.2) 0.666
Digitalis 54 (5.4) 79 (7.9) 130 (13.1) <0.001
Sodium bicarbonate 9 (0.9) 8 (0.8) 30 (3.0) <0.001
Hydration 478 (47.8) 409 (40.9) 428 (42.8) 0.006
LVEF (%) 68.097.25 60.705.27 57.537.82 <0.001
Serum creatinine (mol/L)
Baseline 90.3211.78 87.9911.83 106.6430.94 <0.001
Post-procedural 87.6814.63 85.7314.88 104.2838.83 <0.001
eGFR (mlmin
1.73 m
Baseline 79.9511.53 78.1110.55 64.7117.46 <0.001
Post-procedural 84.2516.44 82.3319.41 68.3120.43 <0.001
AGEF score 0.800.09 1.040.07 1.160.45 <0.001
Values are expressed as mean standard deviation or number (percentage). ACEI: angiotensin-converting enzyme inhibitor; LVEF: left ventricular ejection fraction;
eGFR: estimated glomerular fltration rate; AGEF: age, estimated glomerular fltration rate and ejection fraction.
Table 2. Incidence of CIAKI and clinical event in different AGEF
(n=1 006)
(n=1 000)
P values
CIAKI (n (%)) 11 (1.1) 23 (2.3) 58 (5.8) <0.001
Clinical events (n (%))
All-cause deaths 0 (0) 1 (0.1) 7 (0.7) 0.004
Worsening heart failure
23 (2.3) 36 (3.6) 44 (4.4) 0.029
Dialysis/hemofltration 0 (0) 0 (0) 2 (0.2) 0.132
Defned as increment of NYHA classifcation 1 grade. CIAKI: contrast induced
acute kidney injury; AGEF: age, estimated glomerular fltration rate and ejection
Chinese Medical Journal 2014;127 (12) 2335
With the rapid development of interventional cardiology,
CIAKI has become one of the most important causes of
acquired kidney injury in clinical practice.
to previous literature, CIAKI is associated with increased
cardiovascular morbidity and mortality, as well as
prolonged hospitalization and medical cost.
to identify high risk patients, and to prevent CIAKI by
prophylactic measures in that cohort, has great clinical
signifcance. In the present study, all patients had DM and
CKD, the two important risk factors of CIAKI, which is
ripe for rigorous risk stratifcation.
Several validated risk assessment scoring models have been
established, including the Mehran risk score (MRS) and
AGEF score.
The AGEF score, which is derived from
the age, creatinine and ejection fraction (ACEF) score, has
proven effective in predicting long-term adverse cardiac
events after PCI.
In recent years, it has also been validated
as a good predictor of CIAKI in patients undergoing PCI.

Different from other complicated risk assessing models,
the AGEF scoring model is built based on the rule of
parsimony and consists of only three variables, i.e. age,
eGFR, and ejection fraction, which makes it easy to obtain
the necessary information and calculate the score.
The present study was a post hoc analysis of the TRACK-D
study population. It is a study to validate the diagnostic
efficacy of the AGEF score in predicting CIAKI in a
population with DM concomitant CKD undergoing
coronary/peripheral arterial angiography. There were two
major differences between the TRACK-D population and
other AGEF score validation populations. First, patients
enrolled in this study were all diabetic, which accounted
for only about 25%30% of the whole population in
other studies.
Moreover, mild to moderate renal
function impairment (eGRF 30%90%), which directly
influences the AGEF score, was observed in all patients
in the present study, indicating a cohort with higher risk
of CIAKI. Second, different from the fact that all patients
had undergone PCI in other studies, patients with PCI
accounted for only 53% of the patients in the present study,
which implied less contrast medium use (median 110120
ml) but more similarity to clinical practice. The above two
characteristics imposed apparently contradictory impacts
on the risk of CIAKI, which increased the uncertainty of
CIAKI risk prediction by AGEF score. Our results showed
that the incidence of CIAKI was relevant to AGEF score
with an AUC of 0.70, which was lower than that reported
by Ando et al in a general PCI patient set (AUC 0.88).

The different results of the two studies might be explained
by the differences between the study populations. Given
the complexity of the TRACK-D population in clinical
practice, using AGEF score as a predictor of CIAKI is
acceptable and might be helpful for making decisions.
According to the specifics of the study population, some
important factors in other risk scoring systems, such as
diabetes and the amount of contrast, had less signifcance
for assessing risk.
In the present study, we have found that the AGEF
score gradients were associated with not only the risk of
CIAKI, but also the occurrence of clinical events such
as all cause death and worsening heart failure. Although
CIAKI has proven to be related to increased morbidity and
the causality between CIAKI and clinical
events cannot be confirmed in this study, because of the
signifcantly different baseline characteristics in the low to
high AGEF score tertiles. The impact of CIAKI on clinical
events needs further investigation with a longer follow-up
Several limitations should be mentioned for the present
study. First, this study was a post hoc analysis of a
randomized study with strict inclusion and exclusion
criteria. Half of patients were randomly assigned to receive
rosuvastatin for fve days during the operative period. An
iso-osmolar, nonionic contrast medium, iodixanol, was
used identically in both groups. Therefore, readers should
be cautioned that the conclusion is not derived from a real
Table 3. Independent predictors of CIAKI: multivariate analysis
Variables OR 95% CI P values
AGEF score 4.96 2.32, 10.58 <0.01
Male 1.48 0.87, 2.50 0.14
Age 0.98 0.95, 1.01 0.18
Diabetes history 0.89 0.67, 1.18 0.42
Body mass index 0.99 0.91, 1.07 0.73
Acute coronary syndromes 1.62 0.98, 2.67 0.06
eGFR (<60 mlmin
1.73 m
) 1.04 1.03, 1.06 <0.01
Ejection fraction 0.88 0.85, 0.91 <0.01
Hemoglobin 0.98 0.97,0.99 0.04
Hydration 0.99 0.61, 1.60 0.95
Rosuvastatin 0.54 0.33, 0.88 0.01
ACEI/ARB 1.20 0.62, 2.32 0.59
Beta-blocker 0.93 0.52, 1.67 0.80
CIAKI: contrast induced acute kidney injury; AGEF: age, estimated glomerular
filtration rate and ejection fraction; ACEI: angiotensin converting enzyme
inhibitor; ARB: angiotensin receptor inhibitor; eGFR: estimated glomerular
fltration rate.
Figure 1. ROC curve for AGEF score. ROC: receiver operating
characteristic; AGEF: age, estimated glomerular filtration rate
and ejection fraction.
Chin Med J 2014;127 (12) 2336
world setting. Second, all patients in the present study had
mild to moderate renal function reduction, which may
directly influence the distribution of the AGEF score and
cause subsequent inaccuracies of the model. However, mild
to moderate renal function reduction represents a marginal
risk of CIAKI and is the major reason for difficulties
in decision making. Therefore, results of the present
study might have potential clinical meanings for CIAKI
identifcation and prevention in such patient cohort.
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(Received December 8, 2013)
Edited by Wang Mouyue and Liu Huan