ORIGINAL ARTICLE

Response of urinary liver-type fatty acid-binding proteinto contrast media administration has a potential to predictone-year renal outcome in patients with ischemic heart disease

Daishi Fujita • Masao Takahashi • Kent Doi • Mitsuru Abe • Junichi Tazaki •

Arihiro Kiyosue • Masahiro Myojo • Jiro Ando • Hideo Fujita • Eisei Noiri •

Takeshi Sugaya • Yasunobu Hirata • Issei Komuro

Received: 13 November 2013 / Accepted: 31 January 2014

� Springer Japan 2014

Abstract Urinary liver-type fatty acid-binding proteins

(uL-FABP) have recently been recognized as a useful

biomarker for predicting contrast-induced nephropathy.

Although accumulating studies have evaluated short-term

outcomes, its prognostic value for long-term renal prog-

nosis in patients undergoing coronary angiography (CAG)

has not been fully examined. This study aimed to evaluate

the predictive value of uL-FABP for long-term renal out-

come in patients with ischemic heart disease (IHD). Con-

secutive 24 patients with impaired renal function (serum

creatinine [1.2 mg/dL) who underwent CAG were

enrolled. uL-FABP was measured before CAG, 24 and

48 h after CAG. The changes in estimated glomerular fil-

tration rate (eGFR) throughout CAG and at 1 year later

were compared with the uL-FABP levels. The patients with

a greater decrease in eGFR 1 year later had higher uL-

FABP levels at all points, but only the value at 48 h after

CAG reached statistical significance (lower vs. higher

decreased eGFR group, 4.61 ± 3.87 vs. 17.71 ± 12.96;

P \ 0.01). Measurement of uL-FABP at 48 h after CAG

(48h-uL-FABP) showed better correlation with the change

in eGFR (pre-CAG uL-FABP vs. 48h-uL-FABP: R = 0.27,

P = 0.20 vs. R = 0.65, P \ 0.01). Moreover, the high-pre

and high-48h-uL-FABP group showed a significantly lar-

ger decrease in eGFR compared with the high-pre and low-

48h-uL-FABP group (change in eGFR; 8.12 ± 4.06 vs.

1.25 ± 2.23 mL/min/1.73 m2, P \ 0.01), although the

baseline eGFR levels were similar between these two

groups. In this pilot study, measurement of uL-FABP levels

at 48 h after CAG may be useful in detecting renal damage,

and in predicting 1-year renal outcome in IHD patients

undergoing CAG.

Keywords Urinary liver-type fatty acid-binding proteins

(uL-FABP) � Renal prognosis � Coronary angiography

(CAG) � Contrast-induced nephropathy (CIN)

Abbreviations

uL-FABP Urinary liver-type fatty acid binding protein

DM Diabetes mellitus

CKD Chronic kidney disease

CAG Coronary angiography

IHD Ischemic heart disease

CIN Contrast-induced nephropathy

sCr Serum creatinine

eGFR Estimated glomerular filtration rate

Electronic supplementary material The online version of thisarticle (doi:10.1007/s00380-014-0484-9) contains supplementarymaterial, which is available to authorized users.

D. Fujita � M. Takahashi (&) � A. Kiyosue � M. Myojo �J. Ando � H. Fujita � I. Komuro

Department of Cardiovascular Medicine, Graduate School

of Medicine, The University of Tokyo, Hongo 7-3-1,

Bunkyo-ku, Tokyo 113-8655, Japan

e-mail: masaotakahashi-gi@umin.org

K. Doi � E. Noiri

Division of Nephrology, Graduate School of Medicine,

The University of Tokyo, Hongo 7-3-1, Bunkyo-ku,

Tokyo 113-8655, Japan

M. Abe

Department of Cardiology, Kyoto Medical Center, Kyoto, Japan

J. Tazaki

Department of Cardiovascular Medicine, Graduate School

of Medicine, Kyoto University, Kyoto, Japan

T. Sugaya

CMIC Company, Limited, Tokyo, Japan

Y. Hirata

Tokyo Teishin Hospital, Tokyo, Japan

123

Heart Vessels

DOI 10.1007/s00380-014-0484-9

Introduction

Liver-type fatty acid-binding protein (L-FABP) is a 14.4-

kDa protein expressed in the proximal tubule of human

kidney [1]. It binds to free fatty acids (FFA), which are

reported to be overloaded in the proximal tubule in various

conditions leading to tubulointerstitial damage, such as

massive proteinuria, ischemia, and toxic insults. FFAs

induce L-FABP gene expression, and L-FABP is thought to

be the regulator of FFA homeostasis in the cytoplasm.

Because measuring urinary L-FABP (uL-FABP) enables us

to monitor renal tubulointerstitial damage [2, 3], uL-FABP

has recently been recognized as a useful biomarker for

renal impairment. A number of clinical studies that eval-

uated uL-FABP have been reported with cohorts of patients

with diabetes mellitus (DM) [4–7], chronic kidney disease

(CKD) [8], kidney transplantation, cardiovascular surgery

[9, 10], and under critical care [11–14].

Coronary angiography (CAG) has become indispensable

to the evaluation and management of patients with ischemic

heart disease (IHD). Renal impairment is an important risk

factor for IHD, but many patients with coronary ischemia

have renal impairment. Although prophylactic measures for

contrast-induced nephropathy (CIN) have been widely

explored and its efficacies have been shown, it is still dif-

ficult to determine the risks and benefits of performing CAG

in each individual patient. uL-FABP has been reported as a

promising prognostic indicator for CIN occurrence [15–19],

but its effect on renal function over a longer period has not

been evaluated. Many patients undergo CAG several times,

and a useful biomarker that can predict future progression of

renal injury due to contrast medium administration is

important. We measured periprocedural uL-FABP in CAG

patients and examined whether measuring uL-FABP would

be useful in detecting patients who are susceptible to tubu-

lointerstitial damage after contrast medium administration.

We also evaluated the performance of uL-FABP for pre-

dicting the long-term renal outcomes of patients who were

exposed to contrast media.

Methods

Study design and patient enrollment

This study was designed as a part of the BLOCKADE

study (UMIN-CTR ID C000000419), in which the effect of

intravenous sodium hydrogen carbonate (NaHCO3) for the

prevention of CIN was examined. Patients suspected of

having IHD with serum creatinine (sCr) levels above

1.2 mg/dL and who underwent elective CAG at our insti-

tute were enrolled. Exclusion criteria were acute coronary

syndrome, planned dialysis, severe heart failure not toler-

ating hydration, and administration of contrast medium

within 72 h of CAG. To prevent CIN, CAG was performed

under either intravenous 0.9 % sodium chloride (NaCl;

1 mL/kg/h, 12 h before CAG until 12 h after CAG), or

intravenous NaHCO3 (3 mL/kg/h for 1 h before CAG and

1 mL/kg/h for 6 h after CAG). N-acetylcysteine

(704.8 mg/day; twice a day) was administered at the phy-

sician’s discretion on the previous day and the day of CAG.

CIN was defined as a relative increase in sCr concentration

of at least 25 % or an absolute increase in sCr of 0.5 mg/dL

at 48 h after CAG. The levels of uL-FABP were measured

on the day before CAG (pre-uL-FABP), 24 h after CAG

(24h-uL-FABP), and 48 h after CAG (48h-uL-FABP) by

specific enzyme-linked immunosorbent assay. sCr was

measured on the same day of uL-FABP. After discharge,

the patients were followed up at our outpatient clinic and

their clinical outcomes and sCr were analyzed. Estimated

glomerular filtration rate (eGFR) was calculated using the

Japanese equation for eGFR [20]. Diabetes was defined as

HbA1c [6.5 % in accordance with the National Glycohe-

moglobin Standardization Program and/or taking anti-dia-

betic agents including insulin-use regardless of fasting

glucose levels. Patients were diagnosed with hypertension

when their systolic/diastolic blood pressure on admission

was [140/90 mmHg or when they were under treatment

with antihypertensive agents. Left ventricular ejection

fraction (LVEF) was calculated by echocardiography.

The study protocol was approved by the Institutional

Review Board of the University of Tokyo Hospital

(P2008026-11X). All patients provided written informed

consent before participation.

uL-FABP analysis

For each patient, three urine samples were obtained and

then frozen at -80 �C within 12 h of collection. Urinary

L-FABP was measured using commercially available

ELISA kits (Human L-FABP Assay Kit; CMIC Co Ltd.,

Tokyo, Japan). Briefly, a sandwich is formed of the

L-FABP antigen between the anti-L-FABP antibody coated

at the bottom of a microplate and the free anti-L-FABP

antibody conjugated with peroxidase. Its optimal density is

measured after incubation with substrate to determine the

L-FABP concentration. Urinary L-FABP levels were

evaluated by correction with urine creatinine concentration

as previously described [12].

Data analysis and statistics

Data are presented as the mean ± SD. The Student t test or

Mann–Whitney test was used to compare two groups.

Heart Vessels

123

Univariate and multivariate analyses were performed to

clarify the factors that correlated with the change of eGFR.

These calculations were performed using Dr. SPSS II for

Windows (SPSS Japan, Inc, Tokyo). P \ 0.05 was con-

sidered to be statistically significant.

Results

From January 2009 to March 2010, 24 patients were

enrolled in this study. The clinical backgrounds of these

patients are shown in Table 1. All the enrolled patients

were diagnosed as CKD based on the KDIGO guideline

(i.e., eGFR \60 mL/min/1.73 m2). The underlying disor-

der for CKD was either DM or hypertension in all patients.

There were no significant differences in uL-FABP levels at

any point and eGFR at 1 year later between the NaCl group

and NaHCO3 group (data not shown). The average amount

of contrast medium used for CAG was 60.0 ± 17.9 mL.

The patients who were required the later PCI amounted

to 11. And there was no significant difference in baseline

and followed eGFR levels between required and not

required PCI patients (Supplement Table; eGFR change

rate; no PCI vs. later PCI = 0.96 ± 5.68 vs. 3.20 ± 5.56,

P = 0.34).

Table 2 shows the baseline and follow-up data for renal

function and uL-FABP. There was no CIN occurrence

within the observation period of 48 h in this study. At

1 year from CAG, renal impairment had progressed by

0.10 ± 0.20 mg/dL in sCr and by 2.0 ± 5.5 mL/min/

1.73 m2 in eGFR. The time course of uL-FABP in each

patient is shown in Fig. 1a. In 8 patients, the uL-FABP level

did not change at all, whereas in the remaining 16 patients

the level was significantly increased at 24 h after CAG. The

levels of uL-FABP had almost reverted to the baseline at

48 h after CAG. The patients were divided into two groups

by the median value of eGFR change at 1 year (median;

-1.05 mL/min/1.73 m2). Although both higher and lower

progression in eGFR groups exhibited similar time courses

in terms of uL-FABP values (Fig. 1b, c), the greater eGFR

progression group had higher uL-FABP levels at all points.

In this group, only the 48h-uL-FABP value reached statis-

tical significance. Previous reports showed uL-FABP levels

were positively correlated with urinary albumin levels [21].

We did not collect the levels of the urinary albumin in all

patients, but only 8 patients were available the urinary

albumin levels. In these patients, the pre-uL-FABP had a

correlation with urinary albumin values (supplemental fig-

ure: R = 0.90, P = 0.003). Urinary albumin value reflected

the pre-uL-FABP, as well as previous report.

Regression analysis revealed the following parameters

to be risk factors for a long-term decrease in eGFR for

1 year: higher 48h-uL-FABP levels and higher baseline

Cystatin C level (Table 3). Pre-uL-FABP and 24-h-uL-

FABP levels were not statistically significant, although

levels of 48h-uL-FABP were significantly correlated with a

decrease in eGFR (Fig. 2a, b, c). The amount of contrast

medium was not a significant risk for renal outcome in our

analysis.

To confirm the predictive value of uL-FABP for renal

outcome at 1 year, the patients were divided into two

groups by the median value of uL-FABP measured at each

time point, and the changes in eGFR were compared

(Table 4). The patients in the higher uL-FABP group

showed a significantly larger decrease of eGFR compared

Table 1 Background of patients in this study

Patients background

n 24

Age 69.9 ± 8.5

Female 2 (8 %)

Height (cm) 163.0 ± 6.4

Weight (kg) 65.3 ± 12.9

BMI 24.5 ± 4.2

DM 16 (66.7 %)

CHF 3 (12.5 %)

HTN 24 (100 %)

PAD 3 (12.5 %)

pPCI 15 (62.5 %)

pCABG 3 (12.5 %)

Diseased vessels

Average 2.17

1 5

2 10

3 9

ACE-I 6 (25 %)

ARB 16 (66.7 %)

Diuretics 5 (20.8 %)

NSAIDS 2 (8.3 %)

Statin 19 (79.2 %)

Baseline sCr (mg/dL) 1.37 ± 0.20

eGFR (mL/min/1.73 m2) 40.83 ± 7.96

Cystatin C (mg/L) 1.20 ± 0.24

Hb (g/dL) 12.39 ± 1.29

CRP (g/dL) 0.23 ± 0.27

BNP (pg/mL) 87.1 ± 107.5

Overt urinary protein 9 (37.5 %)

LVEF (%) 68.0 ± 9.6

Contrast medium (mL) 60.0 ± 17.9

N-acetylcysteine 21 (87.5 %)

DM diabetes mellitus, CHF congestive heart failure, HTN hyperten-

sion, PAD peripheral artery disease, ACE-I angiotensin-converting

enzyme inhibitors, ARB angiotensin receptor blockers, NSAIDS non-

steroidal anti-inflammatory drugs, BNP brain natriuretic peptide,

LVEF left ventricular ejection fraction

Heart Vessels

123

with the lower group at all time points, although there was

no statistical difference in the baseline eGFR levels

between the groups.

To confirm that the patients with prolonging increase in

uL-FABP have poor renal outcome, the patients with high

(n = 12) and low pre-uL-FABP (n = 12) were further

divided into two groups according to the ratios of their uL-

FABP levels at 24 and 48 h after CAG to pre-uL-FABP

levels (Table 5). The median ratios of 24h- and 48h-uL-

FABP to pre-uL-FABP were 2.8 and 2.0, respectively, in

the lower pre-uL-FABP group. There was no difference in

eGFR change at 1 year among the subgroups in the lower

pre-uL-FABP group. Among the higher pre-uL-FABP

subgroups, the higher 48h-uL-FABP subgroup exhibited a

significant change in eGFR at 1 year, while the higher 24h-

uL-FABP group did not (Table 5; Fig. 3a, b). The median

ratios of 24h- and 48h-uL-FABP to pre-uL-FABP were 1.8

and 0.8, respectively, in the high pre-uL-FABP group. The

high-pre and high-48h-uL-FABP level groups showed a

significantly larger decrease in eGFR over a year compared

with the high-pre and low-48h-uL-FABP level groups

(Table 5), although the baseline eGFR levels were similar

between these two groups. The patient backgrounds for

these two groups are shown in Table 6. Although the high-

pre and high-48h-uL-FABP groups were slightly older and

had higher brain natriuretic peptide levels, there was no

significant difference in risk factors for renal outcome

between the two groups.

Table 2 Baseline and follow

up renal functionPre CAG 24 h 48 h 1 year

sCr (mg/dL) 1.37 ± 0.20 1.34 ± 0.23 1.41 ± 0.28 1.47 ± 0.31

eGFR (mL/min/1.73 m2) 40.83 ± 7.96 40.77 ± 10.48 42.53 ± 9.72 38.84 ± 9.67

uL-FABP (lg/gCr) 11.82 ± 15.32 24.97 ± 29.33 11.16 ± 11.59

Fig. 1 a uL-FABP levels in study patients at each time point. On

average, uL-FABP levels had doubled at 24 h after CAG and returned

to baseline at 48 h. b uL-FABP levels in 12 patients in which the

eGFR did not decline at 1 year. The average uL-FABP levels were

6.24 ± 10.48 (pre CAG), 13.36 ± 15.88 (24 h), and 4.61 ± 3.87

(48 h). All data are the average ± SD. c uL-FABP levels in 12

patients with worsened eGFR at 1 year. The average uL-FABP levels

were 17.40 ± 17.24 (pre CAG), 36.58 ± 34.63 (24 h), and

17.71 ± 12.96 (48 h). Both groups exhibited a similar time course

change in uL-FABP levels after CAG, but only the uL-FABP level at

48 h was statistically significant (lower vs. higher change in eGFR

group, 4.61 ± 3.87 vs. 17.71 ± 12.96; *P \ 0.01)

Heart Vessels

123

Discussion

Urinary L-FABP is a recently developed renal biomarker

that changes dramatically with contrast medium adminis-

tration. In accordance with a previous report, our data

confirmed a large increase in uL-FABP levels after contrast

medium usage and its levels recovered towards baseline

after 48 h from CAG [15]. uL-FABP has been reported as a

useful marker for predicting the occurrence of CIN, which

is defined by a modest but significant elevation of sCr [22].

The results obtained in this study indicated that this sen-

sitive biomarker would also be useful in detecting mild

renal damage which would not change sCr or eGFR. In

addition, sustained elevation of uL-FABP for 48 h after

CAG was an indicator of poor renal outcome at 1 year.

In this study, CIN, which is defined by an elevation of

sCr, was not observed. This is possibly because the amount

of contrast medium was quite low and sufficient preventive

measures such as N-acetylcysteine and intravenous NaCl or

NaHCO3 administration were taken. Although there was no

significant difference in baseline renal function among the

patients, uL-FABP levels before and after CAG varied

markedly. It is of note that patients with a higher pre-uL-

FABP level or post-uL-FABP level had worse renal out-

come at 1 year. On the other hand, patients whose uL-

FABP levels recovered after CAG had a better long-term

renal outcome. These results may suggest that uL-FABP

could reflect mild renal damage which would not affect

eGFR immediately but have a significant impact on long-

term renal prognosis. It is well known that renal tubular

cell injury will induce inflammatory cell infiltration and

fibrosis and subsequently promote renal dysfunction

Table 3 Univariate and multivariate analyses of eGFR change

Univariateanalysis

Multivariateanalysis

R P value R P value

Gender (female) 0.24 0.25

Age -0.11 0.60

DM 0.15 0.48

Baseline sCr 0.001 1.00

Baseline eGFR 0.002 0.99

Baseline Cystatin C 0.45 0.03 0.39 <0.01

Amount of contrast medium 0.21 0.32

ACE-I -0.25 0.24

ARB 0.33 0.12

Statin 0.27 0.21

Overt urinary protein 0.60 <0.01 0.006 0.712

uL-FABP

Pre CAG 0.27 0.20

24 h 0.27 0.21

48 h 0.65 <0.01 0.46 <0.01

Statistically significant P values are in bold

Fig. 2 a Correlation between change in eGFR and pre-uL-FABP

levels (regression coefficient R = 0.27, P = 0.20). b Correlation

between change in eGFR and uL-FABP level at 24 h (regression

coefficient R = 0.26, P = 0.21). c Correlation between change in

eGFR and uL-FABP level at 48 h (regression coefficient R = 0.65,

P \ 0.01). The levels of uL-FABP at 48 h showed better correlation

with change in eGFR than uL-FABP levels at other time points

Heart Vessels

123

independently from a glomerular lesion. Because L-FABP

in urine is dominantly derived from renal tubular cells, it is

quite possible that the measurement of uL-FABP will

enable clinicians to monitor the stress or injury to renal

tubular cells [21, 23, 24].

Although eGFR did not change through CAG in this

study, uL-FABP can detect minor impairment in kidney

and can clinically be important for the management of

patients with CKD. We speculate that measuring uL-FABP

after CAG enables us to identify the high-risk patients who

would have further renal dysfunction 1 year later. In our

study, uL-FABP levels at 48 h after CAG seemed to be the

most reliable indicator. The pre-uL-FABP and 24h-uL-

FABP levels varied greatly, and there may have been many

influencing factors such as temporary dehydration through

the CAG and excess salt intake during the pre-hospital-

ization. The measured values of 48h-uL-FABP were stable,

perhaps because the measurement conditions were rela-

tively uniform. Forty-eight hours is long enough for the

contrast medium used to be washed out of the patient’s

Table 4 eGFR change according to the uL-FABP levels

uL-FABP N eGFR (mL/min/1.73 m2) P value

Baseline 1 year D

Pre

High 12 38.54 ± 10.47 33.87 ± 10.24 -4.68 ± 4.75 0.02

Low 12 43.12 ± 2.58 43.83 ± 5.68 0.71 ± 4.83

24 h

High 12 40.08 ± 10.02 35.64 ± 10.68 -4.44 ± 5.78 0.03

Low 12 41.58 ± 5.02 42.04 ± 7.24 0.46 ± 3.87

48 h

High 12 37.85 ± 9.42 33.41 ± 9.09 -4.44 ± 4.82 0.03

Low 12 43.82 ± 4.49 44.28 ± 6.71 0.46 ± 5.01

eGFR levels at baseline and 1 year for each subgroup are shown. The patients were divided into two groups according to the median value of uL-FABPlevels at each point. The median uL-FABP levels were as follows: pre 3.09, 24 h 13.89, 48 h 6.48, respectively. At every time point, the high groupshowed a larger change in Egfr. There were no statistically significant differences among the baseline eGFR values

Statistically significant P values are in bold

Table 5 eGFR change according to the uL-FABP levels, subgroup analysis

uL-FABP N eGFR (mL/min/1.73 m2) P value

Baseline 1 year D

Pre low

24 h

High 6 43.34 ± 2.40 42.52 ± 7.54 -0.82 ± 6.52 0.33

Low 6 42.91 ± 3.19 45.14 ± 4.04 2.24 ± 2.80

48 h

High 6 43.52 ± 2.36 43.87 ± 7.01 0.35 ± 5.18 0.82

Low 6 42.73 ± 3.18 43.80 ± 5.30 1.06 ± 5.37

Pre high

24 h

High 6 39.20 ± 10.29 35.91 ± 11.39 -3.29 ± 4.18 0.47

Low 6 37.88 ± 10.60 31.80 ± 8.47 -6.08 ± 4.87

48 h

High 6 39.83 ± 10.09 31.72 ± 7.72 -8.12 ± 4.06 <0.01

Low 6 37.25 ± 10.68 36.00 ± 11.88 -1.25 ± 2.23

eGFR values at baseline and 1 year for each subgroup are shown. The patients were divided according to their pre-uL-FABP and then by their post-uL-FABP/pre uLFABP ratio at the median. The pre-low groups had only slight changes in eGFR at 1 year, regardless of their uL-FABP levels at 24 or 48 h. Inthe higher pre-uL-FABP group, patients with high 48h-uL-FABP levels showed the largest and a significant change in eGFR (-8.12 ± 4.06; P \ 0.01).The higher pre and lower 48h-uL-FABP level groups had a favorable renal prognosis. Median ratios of post- to pre-uL-FABP: low-pre and 24 h was 2.8,low-pre and 48 h was 2.0, high-pre and 24 h was 1.8, high-pre and 48 h was 0.8. There were no statistically significant differences among the baselineeGFR

Statistically significant P value is in bold

Heart Vessels

123

body. Furthermore, at 48 h the body fluid volume and salt

intake were relatively constant, so it is also an appropriate

time for measurement from this perspective. Forty-eight

hours after CAG seems to be the right timing for detecting

prolonged damage. Patients with high levels of 48h-uL-

FABP should preferably undergo an examination that does

not use contrast medium, such as RI scintigraphy. The

measurement of 48h-uL-FABP can be useful in optimizing

our method of follow-up after percutaneous coronary

intervention in patients with renal impairment. Conversely,

patients with low uL-FABP levels through CAG may be

able to tolerate repeated contrast medium administration.

Our study has some limitations. First, the conditions in

which each patient’s urine was obtained were not strictly

unified. Basically, the first urine in the morning of day 1 and

day 2 was obtained, but water intake was not limited and the

degree of dehydration may have differed among patients.

We attempted to standardize this by urine creatinine levels.

Our study population was rather small and was limited to

patients with risk factors for IHD. All patients had

hypertension and many patients had DM, and they were

administered the optimal medications. This may have been

the reason why the already known risk factors such as DM

did not reach statistical significance for progression in renal

impairment in our study. A longer period of time is perhaps

needed for other risk factors to become prominent. In

addition, a large-scale multicenter prospective study is

necessary to confirm the result of this study. Despite these

limitations, our results still show that 48h-uL-FABP levels

are a very strong predictor of renal outcome at 1 year after

CAG in patients suspected of having IHD.

In conclusion, the measurement of 48h-uL-FABP levels

may be useful for detecting renal damage after contrast

Fig. 3 Patients with high pre-uL-FABP were further divided into two

groups according to their post-uL-FABP levels: a Subgroups divided

by their uL-FABP levels at 24 h. There was no significant difference

between the two groups in eGFR change at 1 year (-6.08 ± 4.87 vs.

-3.29 ± 4.18, P = 0.47). b Subgroups divided by their uL-FABP

levels at 48 h. While the low 48h-uL-FABP subgroup had good renal

outcome, the high 48h-uL-FABP subgroups showed as much as

-8.12 ± 4.06 change in eGFR at 1 year. *P \ 0.01

Table 6 Background of high pre- and low 48h-uL-FABP group, and

high pre and high 48h-uL-FABP group

Patients background High-low High–high P value

n 6 6

Age 67.7 ± 13.7 72.3 ± 9.8 0.5

Female 1 (16.7 %) 1 (16.7 %) n.s.

Height (cm) 158.6 ± 9.5 161.6 ± 3.7 n.s.

Weight (Kg) 63.4 ± 19.8 62.7 ± 7.7 n.s.

BMI 24.9 ± 6.5 24.1 ± 3.4 n.s.

DM 4 (66.7 %) 4 (66.7 %) n.s.

CHF 1 (16.7 %) 1 (16.7 %) n.s.

HTN 6 (100 %) 6 (100 %) n.s.

PAD 0 (0 %) 2 (33.3 % 0.5

pPCI 3 4 n.s.

pCABG 2 3 n.s.

Average diseased

vessels

2.17 2.33 n.s.

1 2 1

2 1 2

3 3 3

ACE-I 2 (33.3 %) 1 (16.7 %) 0.5

ARB 3 (50 %) 4 (66.7 %) 0.6

Diuretics 2 (33.3 %) 2 (33.3 %) n.s.

NSAIDS 0 (0 %) 0 (0 %) n.s.

Statin 4 (66.7 %) 6 (100 %) 0.5

Baseline sCr (mg/dL) 1.51 ± 0.27 1.38 ± 0.26 0.4

eGFR (mL/min/1.73 m2) 37.25 ± 11.70 39.83 ± 11.05 0.7

Cystatin C (mg/L) 1.20 ± 0.24 1.35 ± 0.19 0.23

Hb (g/dL) 11.93 ± 1.15 12.60 ± 2.00 0.5

CRP (g/dL) 0.36 ± 0.43 0.19 ± 0.15 0.38

BNP (pg/mL) 66.7 ± 75.9 157.9 ± 140.0 0.19

Overt urinary protein 4 (66.7 %) 5 (83.3 %) 0.5

LVEF (%) 67.0 ± 7.5 65.8 ± 6.9 0.8

Contrast medium (mL) 67.5 ± 22.1 65.8 ± 6.9 n.s.

N-acetylcysteine 5 (83.3 %) 4 (66.7 %) 0.5

Later PCI 4 (66.7 %) 4 (66.7 %) n.s.

The abbreviations are listed in Table 1

Heart Vessels

123

medium administration and for predicting 1-year renal

outcome in patients undergoing CAG.

Conflict of interest There are no conflicts of interest, and there was

no source of support for this article.

References

1. Kamijo-Ikemori A, Sugaya T, Kimura K (2006) Urinary fatty

acid binding protein in renal disease. Clin Chim Acta 374:1–7

2. Kamijo A, Sugaya T, Hikawa A, Okada M, Okumura F, Yama-

nouchi M, Honda A, Okabe M, Fujino T, Hirata Y, Omata M,

Kaneko R, Fujii H, Fukamizu A, Kimura K (2004) Urinary

excretion of fatty acid-binding protein reflects stress overload on

the proximal tubules. Am J Pathol 165:1243–1255

3. Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda

T, Kimura K (2009) Urinary excretion of liver type fatty acid

binding protein accurately reflects the degree of tubulointerstitial

damage. Am J Pathol 174:2096–2106

4. von Eynatten M, Baumann M, Heemann U, Zdunek D, Hess G,

Nawroth PP, Bierhaus A, Humpert PM (2010) Urinary L-FABP

and anaemia: distinct roles of urinary markers in type 2 diabetes.

Eur J Clin Invest 40:95–102

5. Kamijo-Ikemori A, Sugaya T, Yasuda T, Kawata T, Ota A,

Tatsunami S, Kaise R, Ishimitsu T, Tanaka Y, Kimura K (2011)

Clinical significance of urinary liver-type fatty acid-binding

protein in diabetic nephropathy of type 2 diabetic patients. Dia-

betes Care 34:691–696

6. Chou KM, Lee CC, Chen CH, Sun CY (2013) Clinical value of

NGAL, L-FABP and albuminuria in predicting GFR decline in

type 2 diabetes mellitus patients. PLoS One 8:e54863

7. Panduru NM, Forsblom C, Saraheimo M, Thorn L, Bierhaus A,

Humpert PM, Groop PH (2013) Urinary liver-type fatty acid-

binding protein and progression of diabetic nephropathy in type 1

diabetes. Diabetes Care 36(7):2077–2083

8. Ivanisevic I, Peco-Antic A, Vulicevic I, Hercog D, Milovanovic

V, Kotur-Stevuljevic J, Stefanovic A, Kocev N (2013) L-FABP

can be an early marker of acute kidney injury in children. Pediatr

Nephrol 28(6):963–969

9. Matsui K, Kamijo-Ikemori A, Sugaya T, Yasuda T, Kimura K

(2012) Usefulness of urinary biomarkers in early detection of

acute kidney injury after cardiac surgery in adults. Circ J

76:213–220

10. Liu S, Che M, Xue S, Xie B, Zhu M, Lu R, Zhang W, Qian J, Yan

Y (2013) Urinary L-FABP and its combination with urinary

NGAL in early diagnosis of acute kidney injury after cardiac

surgery in adult patients. Biomarkers 18:95–101

11. Doi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T,

Yahagi N, Sugaya T, Noiri E (2011) Evaluation of new acute

kidney injury biomarkers in a mixed intensive care unit. Crit Care

Med 39:2464–2469

12. Katagiri D, Doi K, Honda K, Negishi K, Fujita T, Hisagi M, Ono

M, Matsubara T, Yahagi N, Iwagami M, Ohtake T, Kobayashi S,

Sugaya T, Noiri E (2012) Combination of two urinary biomarkers

predicts acute kidney injury after adult cardiac surgery. Ann

Thorac Surg 93:577–583

13. Cho E, Yang HN, Jo SK, Cho WY, Kim HK (2013) The role of

urinary liver-type fatty acid-binding protein in critically ill

patients. J Korean Med Sci 28:100–105

14. Tsigou E, Psallida V, Demponeras C, Boutzouka E, Baltopoulos

G (2013) Role of new biomarkers: functional and structural

damage. Crit Care Res Pract 2013:361078

15. Nakamura T, Sugaya T, Node K, Ueda Y, Koide H (2006) Uri-

nary excretion of liver-type fatty acid-binding protein in contrast

medium-induced nephropathy. Am J Kidney Dis 47:439–444

16. Kato K, Sato N, Yamamoto T, Iwasaki YK, Tanaka K, Mizuno K

(2008) Valuable markers for contrast-induced nephropathy in

patients undergoing cardiac catheterization. Circ J 72:1499–1505

17. Bachorzewska-Gajewska H, Poniatowski B, Dobrzycki S (2009)

NGAL (neutrophil gelatinase-associated lipocalin) and L-FABP

after percutaneous coronary interventions due to unstable angina

in patients with normal serum creatinine. Adv Med Sci

54:221–224

18. Malyszko J, Bachorzewska-Gajewska H, Poniatowski B, Mal-

yszko JS, Dobrzycki S (2009) Urinary and serum biomarkers

after cardiac catheterization in diabetic patients with stable

angina and without severe chronic kidney disease. Ren Fail

31:910–919

19. Manabe K, Kamihata H, Motohiro M, Senoo T, Yoshida S,

Iwasaka T (2012) Urinary liver-type fatty acid-binding protein

level as a predictive biomarker of contrast-induced acute kidney

injury. Eur J Clin Invest 42:557–563

20. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Ya-

magata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised

equations for estimated GFR from serum creatinine in Japan. Am

J Kidney Dis 53:982–992

21. Abe M, Maruyama N, Suzuki H, Inoshita A, Yoshida Y, Okada

K, Soma M (2013) L/N-type calcium channel blocker cilnidipine

reduces plasma aldosterone, albuminuria, and urinary liver-type

fatty acid binding protein in patients with chronic kidney disease.

Heart Vessels 28(4):480–489

22. Katoh H, Nozue T, Kimura Y, Nakata S, Iwaki T, Kawano M,

Kawashiri M, Michishita I, Yamagishi M (2013) Elevation of

urinary liver-type fatty acid-binding protein as predicting factor

for occurrence of contrast-induced acute kidney injury and its

reduction by hemodiafiltration with blood suction from right

atrium. Heart Vessels. doi:10.1007/s00380-013-0347-9

23. Remuzzi G, Benigni A, Remuzzi A (2006) Mechanisms of pro-

gression and regression of renal lesions of chronic nephropathies

and diabetes. J Clin Invest 116:288–296

24. Nath KA (1992) Tubulointerstitial changes as a major determi-

nant in the progression of renal damage. Am J Kidney Dis

20:1–17

Heart Vessels

123