Nephrol Dial Transplant (2006) 21: 715–720
doi:10.1093/ndt/gfi214
Advance Access publication 25 October 2005
Original Article
Ultrasonographic measurement of intima-media thickness
of radial artery in pre-dialysis uraemic patients: comparison
with histological examination
Young Mi Ku2, Young Ok Kim1, Ji Il Kim3, Yeong Jin Choi4, Sun Ae Yoon1, Young Soo Kim1,
Sun Wha Song2, Chul Woo Yang1, Yong Soo Kim1, Yoon Sik Chang1 and Byung Kee Bang1
1
Department of Internal Medicine, 2Radiology, 3General Surgery, 4Clinical Pathology, College of Medicine,
The Catholic University of Korea, Seoul, Korea
Abstract
Background. Increased intima-media thickness (IMT)
of the radial artery is associated with early failure of
radiocephalic arteriovenous fistula (AVF) in haemodialysis patients. Therefore, non-invasive measurements of radial artery IMT before AVF operations
are very important in predicting AVF patency. This
study was designed to evaluate the accuracy of highresolution ultrasonography in measuring radial artery
IMT in pre-dialysis uraemic patients.
Methods. This study enrolled 43 pre-dialysis uraemic
patients awaiting radiocephalic AVF operations for
the first time. In this study, 17 age- and sex-matched
uncomplicated hypertensive patients and 15 healthy
subjects were included as a control. We measured the
internal diameter (ID) and IMT of the radial artery
using high-resolution ultrasonography on the wrists of
uraemic patients as well as the control group before the
AVF operation. We obtained specimens of the radial
artery during the AVF operation and directly measured the IMT by histological examination.
Results. The radial artery IMT of the uraemic patients
(0.41±0.09 mm) was significantly thicker, compared
to both those of the hypertensive (0.33±0.05 mm,
P<0.001) and the healthy patients (0.25±0.04 mm,
P ¼ 0.002). In contrast, the radial artery ID in the
uraemic patients (1.85±0.48 mm) was smaller than
both that of the hypertensive patients (2.08±0.31 mm,
P ¼ 0.023) and the healthy persons (2.34±0.37 mm,
P ¼ 0.001). Radial artery IMT had a negative correlation with radial artery ID in a total of 73 subjects
(r ¼ 0.290, P ¼ 0.012). The value of the radial arterial
IMT measured by sonographic examination correlated
significantly with that by histological examination in
Correspondence and offprint requests to: Young Ok Kim,
Department of Internal Medicine, Uijongbu St. Mary’s Hospital,
The Catholic University of Korea, 65-1, Kumoh-Dong, UijongbuCity, Kyunggi-Do, 480-130, Korea. Email: [email protected]
43 uraemic patients (r ¼ 0.786, P<0.001) and it
correlated significantly with early AVF failure
(r ¼ 0.358, P ¼ 0.027).
Conclusion. Our data suggest that high-resolution
ultrasonography is an effective tool in measuring
radial artery IMT in uraemic patients before AVF
operation.
Keywords: arteriovenous fistula; haemodialysis;
intima-media thickness; ultrasonography
Introduction
It has been recommended that the radiocephalic
arteriovenous fistula (AVF) should be the first choice
for vascular access for haemodialysis (HD) [1–3].
However, it continues to have a high incidence of
early failure, which causes a decrease in the placement
of the AVF [4–7]. The cause of most early failures is
often unknown although the quality of the radial artery
is thought to play an important role [5,8]. As a possible
cause, we have reported that pre-existing intimal
hyperplasia of the artery, which represents arteriosclerosis of the radial artery, is closely associated with
early failure of radiocephalic AVF [9]. However, there
is no available non-invasive method to examine the
presence or absence of the intimal hyperplasia before
the AVF operation.
The arterial wall is composed of three layers: intima,
media and adventitia. Of the three layers, intima-media
thickness (IMT) represents the actual arterial wall and
can be easily measured by high-resolution ultrasonography [10]. The increased IMT of the carotid artery is
well known to be a non-invasive independent risk factor
of cardiovascular mortality, which is easily assessed
by high-resolution ultrasonography [11–15]. In recent
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Y. M. Ku et al.
studies, we have found that increased IMT of the radial
artery by histological examination is associated with
early failure of radiocephalic AVF in HD patients [16].
Therefore, if a noninvasive method to detect radial
artery IMT is performed before the operation, it would
be a great aid to decide on an adequate site for the
AVF. We designed this study to: (1) compare the IMT
of the radial artery among uraemic patients, uncomplicated hypertensive patients and healthy subjects by
using ultrasonographic measurements, and (2) evaluate
the accuracy of ultrasonographic measurements of
radial artery IMT by comparing them with histological
measurements in uraemic patients.
Patients and methods
Patient population
This study enrolled 43 pre-dialysis uraemic patients awaiting their first radiocephalic AVF operation at Uijongbu
St Mary’s Hospital between October 2002 and April 2004.
Patients who received all synthetic grafts and native AVF
operations on the upper arm were excluded from this study.
Out of the 43 uraemic patients, 35 patients (81.4%) had
hypertension. The primary renal disease consisted of diabetic
nephropathy (n ¼ 23), chronic glomerulonephritis (n ¼ 13),
hypertensive nephropathy (n ¼ 5), polycystic kidney disease
(n ¼ 1), and unknown (n ¼ 1). Subjects for the study included
17 age- and sex-matched uncomplicated essential hypertensive
patients (age; 54±7 years, female %; 52.9%) and 15 healthy
persons (age; 57±11 years, female %; 53.3%) used as a
control group. Uncomplicated essential hypertension was
defined as hypertension without any complications such as
diabetes mellitus, coronary artery disease, cerebrovascular
disease, peripheral vascular disease and renal disease.
Measurement of IMT and internal diameter (ID)
of radial artery by ultrasonographic examination
High-resolution ultrasonography was used to measure the
radial artery on the wrist of uraemic patients before the AVF
operation and of control subjects. The examiner was confined
to one skilled radiologist to avoid inter-observer variability,
using a 12 MHz linear transducer with an HDI 5000 unit
(Advanced Technology Laboratory, Bothell, WA). We
measured radial artery IMT and ID twice and calculated
mean values. The IMT was measured at the posterior wall
of the radial artery just above the wrist on a longitudinal
ultrasound image. The IMT was defined as the distance
between blood-intima and media-adventitia interfaces and the
ID was defined as the distance between blood-intima
interfaces of anterior and posterior walls (Figure 1).
Fig. 1. B-mode ultrasonography shows intima-media thickness
(IMT) and internal diameter of the radial artery in a uraemic
patient and a healty person. IMT is the distance between bloodintima and media-advantitia interface at the far wall of the straight
portion at the just above the wrist. See increased IMT of the
uraemic patient, compared to the control.
Fig. 2. Histologic examination of radial arterial wall. IMT means
the sum of intima and media thickness.
by a pathologist who was oblivious to the clinical data.
IMT was measured as the sum of intima and media layers
(Figure 2).
Follow-up of AVF patency for 1 year after
the operation
AVF patency was prospectively followed-up for 1 year
after the operation. First cannulation through the AVF for
HD was individualized according to the state of venous
maturation 4 weeks after the operation. AVF failure was
defined as complete obstruction of the AVF or low blood
flow insufficient to support a dialysis flow rate of 200 ml/min.
Statistics
Measurements of radial artery IMT by histologic
examinations
The AVF operation was performed using the method of end
vein to side artery anastomosis under local anaesthesia.
During the operation, a 10 mm long specimen of the radial
artery wall was obtained at the incision site and stained with
haematoxylin, eosin and trichrome. Slides were examined
All data was expressed with means±SD. A comparison of
mean values of the arterial measurements between uraemic
and control groups and between diabetic and non-diabetic
uraemic patients was made by using non-parametric Mann–
Whitney test. The correlation between the radial artery ID
and the IMT values and the correlation of the IMT values
between ultrasonographic and histological methods, and
Intima-media thickness of radial artery in uraemic patients
717
Table 1. The comparison of clinical factors among the uraemic
patients, hypertensive patients and healthy subjects
Age (years)
Sex (female %)
Smoking (%)
Total cholesterol (mg/dl)
Albumin (mg/dl)
Normal
(n ¼ 15)
HBP
(n ¼ 17)
ESRD
(n ¼ 43)
54±7
52.9
23.5
179±46
4.1±0.5
57±11
53.3
20.0
190±25
4.1±0.5
57±13
47.8
23.2
187±33
3.5±0.5*
*P<0.001, vs normal and HBP. Normal, healthy subjects; HBP,
hypertensive patients; ESRD, uraemic patients.
between IMT values and AVF failure were evaluated
by Spearman’s correlation test. P<0.05 was considered
significant.
Results
Fig. 3. The comparison of radial artery IMT measured by
ultrasonographic examination among the uraemic patients, hypertensive patients, and healthy persons. See increased IMT of
the uraemic patients, compared to the hypertensive patients and
healthy person. *P ¼ 0.002 vs control, **P<0.001 vs HBP,
#
P<0.001 vs control.
Clinical characteristics in the uraemic
and the control groups
The mean age of the uraemic patients was 57±13 years
(33–78 years) and the number of females was
23 (53.4%). There was no difference in age, sex,
incidence of smoking, and serum cholesterol level
among the uraemic patients, hypertensive patients
and healthy subjects. Serum albumin levels in the
uraemic patients were higher than those in the hypertensive patients (P<0.001) and the healthy subjects
(P<0.001) (Table 1).
Comparison of radial artery IMT and ID values
measured by ultrasonography between the
uraemic and the control groups
Mean values of radial artery IMT measured by highresolution ultrasonography in the uraemic patients,
hypertensive patients, and healthy persons were 0.41±
0.09 mm (0.3–0.7 mm), 0.33±0.05 mm (0.25–0.39 mm)
and 0.25±0.04 mm (0.19–0.35 mm), respectively. The
radial artery IMT of the uraemic patients was
significantly thicker, compared to both those of the
hypertensive (P<0.001) and the healthy patients
(P ¼ 0.002). The radial artery IMT in the hypertensive
patients was also thicker than the healthy subjects
(P<0.001) (Figure 3). Radial artery ID in the uraemic
patients (1.85±0.48 mm) was smaller than both that in
the hypertensive patients (2.08±0.31 mm, P ¼ 0.023)
and that in the healthy persons (2.34±0.37 mm,
P ¼ 0.001). The radial artery ID in the hypertensive
patients was also smaller than that in the healthy
persons (P ¼ 0.039) (Figure 4). The radial artery IMT in
the diabetic uraemic patients (n ¼ 23) was thicker than
that in the non-diabetic uraemic patients (n ¼ 20)
(0.44±0.09 mm vs 0.38±0.08 mm, P ¼ 0.032). But
there was no difference in the radial artery ID between
the two groups (1.92±0.41 mm vs 1.79±0.53 mm,
P ¼ 0.212).
Fig. 4. The comparison of radial artery ID measured by ultrasonographic examination among the uraemic patients, hypertensive
patients, and healthy persons. *P ¼ 0.001, vs control, **P ¼ 0.023,
vs HBP, #P ¼ 0.039, vs control.
Correlation between radial artery ID and
IMT values in total subjects (n ¼ 75)
We evaluated the correlation between radial artery ID
and radial artery IMT in total subjects (n ¼ 75). There
was a significant negative correlation between ID with
IMT in all subjects (r ¼ 0.290, P ¼ 0.012) (Figure 5).
Correlation of radial artery IMT between
ultrasonographic and histologic examinations
in 43 uraemic patients
We measured radial artery IMT in the 43 uraemic
patients using histological examination of the arterial
tissues obtained during the AVF operation. The
mean value of radial artery IMT was 0.47±0.10 mm
(0.25–0.70 mm). The value of radial arterial IMT
measured by sonographic examination correlated
significantly with that by histological examination
(r ¼ 0.786, P<0.001) (Figure 6).
718
Y. M. Ku et al.
failed group tended to be smaller than that in the patent
group; however, the difference was not significant
(1.63±0.40 mm vs 1.96±0.52 mm, P ¼ 0.054).
Discussion
Fig. 5. Correlation between radial artery IMT and ID in total 73
subjects.
Fig. 6. Correlation of radial artery IMT by sonographic and
histologic examinations in 43 uraemic patients.
Relationship between radial artery IMT value
and early AVF failure
Of the total 43 patients, five patients died with a patent
AVF within 1 year after the operation. Of the 38 patients
who were alive until the end of the study point, 14
patients experienced AVF failure. We evaluated the
relation between radial artery IMT and AVF failure in
these 38 patients. The IMT value in the failed group
(n ¼ 14) was thicker than that in the patent group
(n ¼ 24) (0.46±0.08 mm vs 0.40±0.09 mm, P ¼ 0.032).
The IMT value correlated significantly with the AVF
failure (r ¼ 0.358, P ¼ 0.027). Radial artery ID in the
The National Kidney Foundation Dialysis Outcome
Quality Initiative (NKF-DOQI) guidelines provide
recommendations that native AVF should be first
constructed for vascular access to improve quality of
life and overall outcomes for HD patients [3]. But
native AVF continues to have a high incidence of early
failure, thus decreasing the popularity of placement of
AVF. Therefore, it is very important to detect before
operation poor quality radial arteries that cause early
AVF failure [4–7]. Doppler ultrasonography is an objective and noninvasive method to assess the quality of
the peripheral vessels [11–15]. Important parameters
of the vessels that can predict AVF failure in predialysis uraemic patients before the operation are small
diameter of the radial artery and cephalic vein, and
low arterial blood flow [5,17,18]. Malovrh [19] have
reported that distension capacity of the artery and vein
as well as the size of the baseline internal diameter are
important to predict AVF patency.
The impact of radial artery IMT on AVF patency
in uraemic patients is not well known. We have
retrospectively studied the impact of radial artery
IMT measured by histologic examination on early
AVF failure within 1 year after the operation in 90
uraemic patients. In the 90 patients, the mean value of
radial artery IMT in the failed group was thicker than
that in the patent group who underwent operation for
AVF. The patients whose IMT was more than 500 mm
had higher incidence of the AVF failure than the
patients whose IMT was less than 500 mm [16]. If we can
detect increased radial artery IMT before the operation, it will be helpful for the surgeon to decide on the
type of vascular access. Based on these findings, we
prospectively performed this study to evaluate the accuracy of ultrasonographic measurements of radial artery
IMT by comparing it with histological measurements in
uraemic patients. This study clearly demonstrated that
radial arterial IMT measured by ultrasonographic
examination was similar to findings done by histological examination. Therefore, we suggest that ultrasonographic examination should be used to measure
the IMT of the radial artery before the AVF operation
in the uraemic patients. This is the first report to
compare radial artery IMT between ultrasonographic
and histological examinations in uraemic patients.
Clinical risk factors of increased intimal hyperplasia
or IMT of the radial artery are known to be old age,
diabetes mellitus, hypertension and atherosclerosis
[9,16,20]. Due to the high incidence of diabetes mellitus,
hypertension and atherosclerosis in uraemic patients,
it is suggested that radial arterial IMT in uraemic
patients may be thicker than that of age-matched
healthy populations. Ejerblad et al. [21] first reported
that the radial arterial wall in HD patients measured by
Intima-media thickness of radial artery in uraemic patients
histological examination was significantly thicker than
that of control subjects. We selected age-, sex-matched
uncomplicated hypertensive patients and healthy subjects as a control and measured radial artery IMT by
ultrasonographic examination. This study showed that
uraemic patients had thicker radial artery IMT than
hypertensive patients and healthy controls.
The IMT can be assessed by B-mode ultrasound and
represents a safe, inexpensive, precise and reproducible
measure [11–15]. But it has the limitation of inter- and
intra-observer variability. In order to minimize these
variables in this study, the examiner was confined to
one skilled radiologist and the IMT was measured twice
for mean values to be calculated. The size of the radial
artery diameter is relatively small; the size of radial
artery IMT is also small and its normal range is known
to be less than 250 mm [20,22]. Therefore, in order to
measure it accurately, ultrasonography needs higher
resolution than a 7.5 MHz transducer. In this study, a
12.5 MHz transducer was used. The AVF operation
was performed uniformly by one vascular surgeon at
the same site (on the wrist) using the same surgical
technique (end-to-side anastomosis) and the pathologic
specimen was evaluated by one pathologist blinded to
clinical data.
In this study, the value of radial arterial IMT
measured by ultrasonographic examination correlated
well with that by histological examination (r ¼ 0.786,
P<0.001). However, some cases showed significant
discrepancy between these two methods. This can be
explained by two causes: the first is due to the sonographic examiner’s inadequate measurement of the
IMT due to small radial artery size, poor ultrasonic
window and wavy arterial course; the second is due to
different measurement sites between ultrasonographic
and histological examinations. The IMT was measured
ultrasonographically on the posterior wall of the radial
artery. In contrast, the radial artery specimen was
obtained on the partial arterial wall at the incision site,
which was usually positioned at the anterior wall.
If there is irregular arterial wall thickening in the
measurement sites of the radial arteries, it could
cause a discrepancy in the IMT between these two
examinations.
In conclusion, increased radial artery IMT is known
to be a risk factor of early AVF failure. Therefore,
it is very important to detect poor quality of the radial
artery before operation in order to enhance the
radiocephalic AVF patency in uraemic patients who
are planning to undergo AVF operation. Our data
suggest that high-resolution ultrasonography is a
simple and effective tool in measuring radial artery
IMT. We recommend that the measurement of radial
artery IMT by ultrasonography be performed in
uraemic patients who have poor vascularity such as
old age, diabetes mellitus, and severe atherosclerosis
before the radio cephalic AVF operation.
Acknowledgements. A part of this study was presented at
the Annual Meeting of the American Society of Nephrology,
San Antonio, MO, 2004. The authors wish to acknowledge the
719
financial support of the Department of Internal Medicine, The
Catholic University of Korea and this work was supported in
part by Gambro Korea Grant 2004 from the Korean Society of
Nephrology.
Conflict of interest statement. None declared.
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Received for publication: 1.7.05
Accepted in revised form: 18.9.05