SaudiJKidneyDisTranspl265924-5911237_162512

Saudi J Kidney Dis Transpl 2015;26(5):924-930
© 2015 Saudi Center for Organ Transplantation
Original Article
Prevalence of Peripheral Arterial Disease Diagnosed by Ankle Brachial
Index among Chronic Kidney Disease Patients in a Tertiary Care Unit
Saeed Laghari, Kifayat Ullah, Imtiaz Masroor, Ghias Butt, Farina Kifayat
Department of Nephrology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
ABSTRACT. The objective of this study is to determine the prevalence of peripheral vascular
disease (PVD) in patients with chronic kidney disease (CKD). Seventy-two patients with CKD
stage 3 or above were included in this study. Blood samples were taken from each patient to
determine complete blood counts, serum albumin, electrolytes, lipid profile and blood sugar
random/fasting. The glomerular filtration rate (GFR) was estimated with the Cockcroft–Gault
formula. The ankle–brachial index (ABI) was determined to identify the presence of PVD. A
standardized Doppler ultrasound device was used. ABI of <0.90 was considered diagnostic of
PVD. The mean age of the patients was 53.22  12.8 years. Forty-six patients (63.9%) were male.
Twenty-five patients (34.7%) were in stage 3 CKD, 20 patients (27.8%) were in stage 4 CKD and
27 patients (37.5%) were in stage 5 CKD. Twenty patients (27.8%) had an ABI <0.9 and hence
had PVD. Of these patients, 13 (18.1%) had mild to moderate PVD with ABI of 0.41–0.90 and
seven (9.7%) had severe PVD with ABI of 0.00–0.40. All the baseline parameters including
systolic blood pressure (BP), diastolic BP, height, weight, body mass index, GFR, hemoglobin,
total blood count, platelets, triglycerides, high-density lipoprotein, low-density lipoprotein and
uric acid were not significantly different between patients with and without PVD (P >0.05). How-
ever, the mean total cholesterol was significantly higher among patients with PVD. The preva-
lence of PVD was significantly high in patients with stage 5 CKD (P <0.05). PVD is frequent
among patients with CKD based on the ABI as measured by Doppler ultrasound.
Introduction
Chronic kidney disease (CKD) is a major pu-
blic health problem worldwide and is associated
Correspondence to:
Dr. Kifayat Ullah,
Department of Nephrology,
Pakistan Institute of Medical Sciences,
Islamabad, Pakistan.
E-mail: drkifayat@gmail.com
with a considerable increase in morbidity and
mortality.1,2
Data from community-based
studies in Pakistan reveal an alarmingly high
burden, at approximately 15–20%, of Pakistani
persons 40 years of age or older having a
reduced estimated glomerular filtration rate
(GFR).3
Cardiac death accounts for almost
40% of the total deaths among CKD patients,
and approximately 20% of these deaths are
due to coronary artery disease.4-6
A recent
study reported that patients with CKD and
Saudi Journal
of Kidney Diseases
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peripheral arterial disease (PAD) had a higher
mortality than patients with either CKD or
PAD alone.7
PAD, which is an important health-care pro-
blem, refers to atherosclerotic and/or thrombo-
embolic processes that affect the aorta, its
visceral arterial branches and arteries of the
lower extremities.8
Intermittent claudication,
manifested by pain in the leg muscles during
ambulation, is the earliest symptom in patients
with PAD.9
PAD has been associated with low
estimated GFR.10
The prevalence of PAD in
the general Pakistani population is reported to
be 18%, while the prevalence of PAD among
patients with CKD in western countries ranges
from 19% to 32%.11,12
Recently, the ankle–brachial index (ABI) has
been recognized as an accurate and reliable
marker of sub-clinical or clinical PAD.13
ABI
is a non-invasive test to screen for PAD, mea-
sured by a hand-held Doppler probe, and is the
ratio between systolic blood pressure (BP) in
the ankle and systolic BP in the arm. Measure-
ment of ABI has shown high sensitivity (95%)
and specificity (100%) for the diagnosis of
PAD in comparison with arteriography, the
gold standard.14
The normal value of the ABI
ranges from 0.9 to 1.3. On the basis of epide-
miological evidence, current guidelines recom-
mend a cut-off of 0.9 for the diagnosis of
PAD.15
This study was performed because no local
published literature is available to show the
prevalence of PAD among CKD patients on
the basis of ABI values. The findings of this
study will help nephrologists and physicians
working in our clinical settings to determine
the burden of PAD among CKD patients and
also help them in offering better management;
thus, improving the outcome of these patients.
Methods
This was an observational study conducted at
the Department of Nephrology, Pakistan Ins-
titute of Medical Sciences (PIMS), Islamabad,
Pakistan. The total duration of the study was
four months. A total of 72 CKD patients were
enrolled in the study. The purposive (non-
probability) sampling technique was used for
study sampling. We included all patients
diagnosed to have CKD of stage 3 or above,
aged above 15 years, both genders, admitted to
the Department of Nephrology, PIMS and
gave consent for being included in the study.
All the patients with CKD aged <15 years,
with stage 1 or 2, were excluded from the
study.
Data were collected through a structured pro-
forma specially designed for this study. Per-
mission was taken from the hospital ethics
committee for conducting the study before the
commencement of study. Those who fulfilled
the inclusion criteria were enrolled. Informed
verbal consent was taken from all the patients
before the enrollment. Each patient with CKD
was allotted a serial number and his/her
hospital number was noted. Further, personal
profile (name, age, gender), causes of CKD
(hypertension, diabetes mellitus, chronic glo-
merulonephritis, obstructive uropathy, heredi-
tary causes) were asked and reported. Each
patient was then assessed clinically, including
examination of peripheral pulses, general phy-
sical examination and systemic examination.
Following this, blood samples were taken from
each patient for laboratory investigations such
as complete blood picture (CBP), serum albu-
min, electrolytes, lipid profile and blood sugar
random/fasting. For this study, GFR was esti-
mated by using the Cockcroft–Gault formula
as follows:
eGFR = [(140 - age) × weight (kg)]/SCr × 72
× (0.85 if female) and adjusted for body
surface area of 1.73 m2
.
In this equation, estimated GFR is expressed
as mL/min per 1.73 m2
and serum creatinine
(SCr) is expressed as mg/dL.
For each patient with CKD, ABI was deter-
mined to assess the presence of PAD. A stan-
dardized Doppler ultrasonic device was used.
BP measurements and ABI calculations were
performed according to the recommendations
of the American Heart Association. Ankle BP
was measured at the posterior tibial artery in
one leg. Two measurements were taken 5–8 min
apart while the participant was in the prone
position. Brachial artery systolic BP measure-
Peripheral arterial disease in CKD patients 925

ments were made 5 min apart with the partici-
pant in the supine position. The ABI was com-
puted by dividing the average of two ankle
systolic BP measurements by the average of
the first two brachial readings. The CKD pa-
tients, with or without PAD, were managed
accordingly. All this information was collected
on the proforma.
Data were analyzed using SPSS version 10.
The descriptive analysis were carried out and
reported as mean with standard deviation and
median for continuous variables such as age of
patients. For categorical variables such as gen-
der, causes of CKD such as diabetes, hyper-
tension, pain in legs, smoking history and
presence of PAD, frequencies and percen-
tages were reported. The comparison of rela-
tive frequency of PAD among the various
stages of CKD (stage 3 onward) was per-
formed using the Chi-square test and P-values
were reported. Likewise, the comparison of
relative frequency of PAD between male and
female patients with CKD was performed
using the Chi-square test and P-values were
reported. The level of significance was selected
at 5% (P-value <0.05).
Results
A total of 72 CKD patients were included in
the study. The age of the patients ranged from
18 to 75 years, with a mean of 53.22  12.8
years. Of all the patients, 46 patients (63.9%)
were male and 26 patients (36.1%) were fe-
male. Twenty-five patients (34.7%) were in
stage 3 CKD with a GFR of 30–60 mL/min,
27.8% were in stage 4 CKD with a GFR of
15–30 mL/min and 27 patients (37.5%) were
in stage 5 CKD with a GFR of <15 mL/min; of
these patients, 25 (34.7%) were on hemo-
dialysis. The ABI ranged from 0.30 to 1.30,
with a mean of 9197  27491.20. 27.8% of the
patients had an ABI <0.9 and hence had PAD.
Thirteen patients (18.1%) had mild to
moderate PAD with ABI of 0.41–0.90 and
seven patients (9.7%) had severe PAD with
ABI of 0.00–0.40 (Table 1).
All the baseline parameters including systolic
BP, diastolic BP, height, weight, body mass
index (BMI), GFR, hemoglobin, total blood
count, platelets, triglycerides, high-density lipo-
protein (HDL), low-density lipo-protein (LDL),
calcium, corrected calcium, phosphate, albumin
and uric acid were not significantly different
between groups with or without PAD (P >0.05,
Table 2). However, the mean total cholesterol
was significantly higher among patients with
PAD. In stage 3 CKD, five of 25 patients
(20%) had PAD, in stage 4 CKD, one of 20
patients (5%) had PAD and in stage 5 CKD, 14
Table 1. Baseline characteristics of the study patients.
Minimum Maximum Mean Std. deviation
Systolic blood pressure 100 200 149.5 24.17
Diastolic blood pressure 70 130 88.61 13.563
Height (cm) 150 167.5 158.57 3.24
Weight (kg) 48 70 59.09 5.25
Body mass index 17.6 33.7 23.79 2.623
Hemoglobin (gm/dL) 5 12 8.9458 1.50
Total leukocyte count (109
/L) 4.30 9.3 6.4264 1.47
Platelets (109
/L) 155 325 222.23 46.19
Cholesterol (mg/dL) 150 280 171.83 28.169
Triglycerides (mg/dL) 54 281 140.31 49.22
High-density lipoprotein (mg/dL) 31 56 45.16 6.61
Low-density lipoprotein (mg/dL) 40 99 64.70 16.16
Uric acid (mg/dL) 4.20 9 5.97 1.16
Calcium (mg/dL) 8.4 10 9.04 0.39
Phosphate (mg/dL) 2.2 4.5 3.26 0.56
Albumin (mg/dL) 3.2 5.5 4.1 0.67
Ankle–brachial index 0.30 1.30 0.91 0.27
926 Laghari S, Ullah K, Masroor I, et al

of 27 patients (51.85%) had PAD (P = 0.001).
Thus, the frequency of occurrence of PAD was
significantly higher in patients with stage 5
CKD.
The mean age of the patients with PAD was
51.9  14.6 years and the mean age of the pa-
tients without PAD was 53.7  12.2 years (P =
0.607). Ten of 46 males (21.74%) and ten of
26 females (38.5%) had PAD (P = 0.107). The
BMI and ABI were inversely related when the
relation was studied with the Pearson corre-
lation coefficient, but the relation was not sta-
tistically significant (P = 0.095, Figure 1).
The causes of CKD in the study patients are
shown in Figure 2.
Discussion
Lower extremity PAD has not been evaluated
in most prior epidemiological studies of car-
diovascular disease among patients with
CKD,16
and very few studies of PAD have
considered CKD as a potential risk factor.17
Thus, knowledge of the epidemiology, out-
comes and treatment options for PAD among
patients with CKD lags behind that for other
forms of cardiovascular disease.
Our study showed that 27.8% of patients had
an ABI <0.9 and hence had PAD. This figure
is higher than that reported for the general po-
pulation. Few prior studies of PAD have inclu-
ded renal insufficiency as a potential corre-
late.18,19
Two studies have focused on a small
sample of patients with advanced CKD, and
they have used intermittent claudication as a
marker of PAD;20,21
according to these studies,
the prevalence of intermittent claudication is
Figure 1. Correlation between the ankle–brachial
index and body mass index in the study patients.
Table 2. Baseline characteristics of patients with and without peripheral arterial disease.
Peripheral arterial
disease (N = 20)
No peripheral arterial
disease (N = 52)
P-value
Age in years 51.95  14.63 53.71  12.26 0.607
Systolic blood pressure 150.75  22.14 149.13  25.10 0.802
Diastolic blood pressure 90.50  13.56 87.88  13.62 0.469
Height (cm) 158.50  2.61 158.60  3.48 0.902
Weight (kg) 59.80  4.38 58.82  5.56 0.485
Body mass index 24.46  2.72 23.53  2.56 0.178
Glomerular filtration rate (mL/min) 21  16.61 29.4  17.77 0.072
Hemoglobin (g/dL) 8.44  1.31 9.13  1.53 0.079
Total leukocyte count (109
/L) 6.41  1.41 6.43  1.50 0.954
Platelets (109
/L) 230.20  51.38 219.17  44.19 0.368
Cholesterol (mg/dL) 194.62  40.92 163.06  14.09 0.00
Triglycerides (mg/dL) 151.6  52.78 135.98  47.59 0.230
High-density lipoprotein (mg/dL) 43.85  7.47 45.67  6.25 0.298
Low-density lipoprotein (mg/dL) 63.9  16.08 65.01  16.33 0.795
Uric acid (mg/dL) 6.06  1.36 5.93  1.09 0.674
Calcium (mg/dL) 9.05  0.38 9.03  0.39 0.897
Phosphate (mg/dL) 3.35  0.53 3.23  0.57 0.450
Albumin (mg/dL) 4.05  0.65 4.11  0.68 0.719

substantially higher among patients with CKD
than in the general population. These studies
looked at PAD on the basis of the symptom of
intermittent claudication; however, we studied
PAD on the basis of ABI. A low ABI is highly
sensitive and specific for the presence of more
than 50% stenosis of lower extremity vessels
on angiography. As mentioned earlier, very
few epidemiologic studies of PAD have con-
sidered CKD as a potential risk factor.17
Among patients enrolled in the United King-
dom Prospective Diabetes Study, albuminuria
was associated with the development of PAD
during study follow-up in univariate, but not in
multivariate, analysis.22
This analysis exa-
mined only albuminuria and not renal func-
tion. Renal insufficiency, defined as a serum
creatinine level >1.3 g/dL in women and >1.5
mg/dL in men, was independently associated
with the development of intermittent claudica-
tion among participants in the community heart
study. Secondary analysis of data from the
Heart and Estrogen/Progestin Replacement
Study showed that both moderate and severe
CKD, defined respectively as an estimated
creatinine clearance of 30–59 and <30 mL/
min/1.73 m2
, respectively, were associated
with an increased risk of arriving at a pre-
defined PAD end-point (revascularization, am-
putation or lower extremity sympathectomy)
during follow-up.23
Established risk factors for PAD include
male sex, older age, diabetes, smoking, hyper-
tension, dyslipidemia (low HDL and high LDL
and triglycerides levels), lipoprotein (a), hyper-
homocysteinemia and chronic inflammation,
whereas alcohol intake and physical activity
seem to be protective.24,25
Among dialysis pa-
tients, many of the risk factors for PAD are the
same as for the general population, but there
also seem to be associations that are unique to
dialysis patients. Webb et al reported that
among 325 hemodialysis patients, intermittent
claudication was associated with older age,
smoking, hypertension and hyper-triglyceri-
demia. Among a sub-group of patients en-
rolled in the HEMO study, Cheung et al26
reported cross-sectional associations of base-
line PAD with smoking, older age, diabetes
and non-black race. In this study, hypertension
and cholesterol were not associated with PAD.
Among patients enrolled in the United States
Renal Data System’s (USRDS) Dialysis Mor-
bidity and Mortality Study (DMMS), coronary
artery disease, cerebrovascular disease, smo-
king, lower diastolic BP, left ventricular hyper-
trophy, lower serum albumin, malnourished
status, lower parathyroid hormone level and
longer time since initiation of dialysis were
associated with baseline PAD, in addition to
age, gender, diabetes and race as reported for
the HEMO study.27
In our study, hypercho-
Figure 2. Causes of chronic kidney disease in the study patients.

lesterolemia was significantly more frequent
among PAD CKD patients and no such diffe-
rence was documented for age, gender, dia-
betes, hypertension or smoking.
In the general population, patients with inter-
mittent claudication are at an increased risk for
death and for cardiovascular events.28
Several
studies have now reported an association bet-
ween an ABI below 0.90 and an increased risk
of both cardiovascular and all-cause mortality
among hemodialysis patients.
The recommendations of the 2005 consensus
document on the management of PAD with
regard to the identification of asymptomatic
PAD and for the evaluation of patients with
intermittent claudication are to be followed.
The main value of identifying patients with
asymptomatic lower extremity PAD is related
to the association of these lesions with an
increased risk of myocardial infarction, stroke
and cardiovascular mortality.29
PAD is con-
sidered to be a coronary equivalent, and such
patients should be treated with risk factor re-
duction. Similar recommendations were made
by the American Diabetes Association for
monitoring asymptomatic patients with dia-
betes.30
Further evaluation is dependent on the
ABI value, with an ABI ≤0.90 being diag-
nostic of PAD. An ABI of 0.91–1.30 should be
followed-up by further testing, such as mea-
surement of the ABI after exercise, segmental
limb pressures or duplex ultrasonography.
Further studies are required to document the
risk factors associated with PAD in the CKD
population as well as the prognostic value of
PAD in predicting cardiovascular outcome in
this population.
Conclusion
PAD is frequent among patients with CKD,
and about one-third of patients with chronic
renal failure have evidence of PAD on ABI as
measured by Doppler ultrasound.
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