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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016
AFRICA
129
Methods
We retrospectively analysed patients with severe PAD who
received iloprost infusion therapy at a dose of 1 ng/kg/min between
January 2011 and January 2012 at Baskent University Hospital,
Ankara, Turkey. Severe PAD was detected with non-invasive
tests, including ankle–brachial index
<
0.40 and absent blood flow
on duplex ultasonography. Among these, 86 patients were selected
according to the following exclusion criteria: (1) malignant
disease, (2) rheumatological or chronic inflammatory disease of
unknown origin, (3) history of systemic vasculitis, (4) unstable
heart failure (ejection fraction
<
50%) during infusion therapy,
(5) chronic liver failure, (6) systemic infective or non-infective
inflammatory diseases, (7) evidence of end-stage renal disease
(ESRD), (8) younger than 18 years of age. An informed consent
was obtained from all subjects of the study.
According to the treatment protocol, patients received iloprost
infusion at a dose of 1 ng/kg/min for 10–14 days. Iloprost in a
100-ml isotonic solution was infused during a six-hour period
via the intravenous route. Nausea, flushing, headache and
thrombophlebitis were recorded as drug-related side effects.
In accordance with the Kidney Disease Improving Global
Outcomes (KDIGO) guidelines, acute kidney injury (AKI) was
defined as
≥
0.3 mg/dl (26.52 μmol/l) increase in creatinine levels
from baseline within 48 hours.
12
The following parameters were collected retrospectively from
clinical charts: (1) age; (2) gender; (3) smoking status; (4)
presence of diabetes, hypertension, dyslipidaemia [serum high-
density lipoprotein cholesterol (HDL-C)
<
40 mg/dl (1.04
mmol/l) and/or low-density lipoprotein cholesterol (LDL-C)
>
130 mg/dl (3.37 mmol/l) and/or triglycerides
>
300 mg/dl (3.39
mmol/l)], or ischaemic heart disease; (4) urinary output; (5) use
of statins, acetylsalicylic acid (ASA), clopidogrel, low-molecular-
weight heparin (LMWH), angiotensin converting enzyme
inhibitors (ACEI), or angiotensin receptor blockers (ARB);
(6) daily systolic, diastolic and mean arterial (2
×
diastolic
pressure + systolic pressure)/3) blood pressure measurement
data; (7) haemoglobin, sodium, potassium, calcium, phosphorus,
albumin, blood urea nitrogen (BUN), creatinine, and estimated
glomerular filtration rate (eGFR) (MDRD equation) values.
Clinical and biochemical parameters were collected before
(baseline), during (third day of infusion therapy) and after (two
weeks after cessation of infusion therapy; 28th day) iloprost
treatment, and mean values were determined as arithmetic
means. Baseline values were defined as those measured at
admission to the in-patient clinic. Office blood pressure levels
were recorded.
Statistical analysis
Statistical analyses were performed using SPSS software
(Statistical Package for the Social Sciences, version 15.0, SPSS
Inc, Chicago, IL, USA). Subjects were grouped according to the
absence of AKI, as the normal renal function group (
n
=
50), and
presence of AKI, as the AKI group (
n
=
36).
Normality of data was analysed using the Kolmogorov–
Smirnov test. All numerical variables with normal distributions
were expressed as means
±
standard deviations (SD), while
variables with skewed distributions were expressed asmedians and
interquartile ranges (IR). Categorical variables were expressed as
percentages and compared using the chi-squared test. Normally
distributed numerical variables were analysed by the independent
samples
t
-test, one-way ANOVA (
post-hoc
Tukey), or paired
samples
t
-test. Numerical variables with a skewed distribution
were compared using the Mann–Whitney
U-
and Kruskal–
Wallis tests. Spearman and Pearson correlation tests were used
for correlation analyses. A binary logistic regression analysis
was performed to assess the major determinant of AKI between
correlated variables. A Kaplan–Meier survival analysis was used
Table 1. Clinical features of the patients
Whole study
group
(
n
=
86)
Patients
with AKI
(
n
=
36)
Patients
without AKI
(
n
=
50)
p-
value
Age (years)
65.82
±
16.7 69.77
±
12.9 64.24
±
17.0 0.109
Male gender,
n
(%)
56 (66.2)
21 (58.3)
35 (70)
0.186
Diabetes mellitus,
n
(%)
48 (55.8)
22 (61.1)
26 (52)
0.221
Hypertension,
n
(%)
84 (97.6)
36 (100)
48 (96)
0.196
Ischaemic heart disease,
n
(%)
40 (46.5)
17 (47.2)
23 (46)
0.542
Dyslipidaemia,
n
(%)
24 (27.9)
10 (27.8)
14 (28)
0.589
Smoking habbit,
n
(%)
43 (50)
14 (38.9)
29 (58)
0.063
ASA,
n
(%)
57 (66.2)
20 (55.6)
37 (74)
0.045
Clopidogrel,
n
(%)
26 (30.2)
12 (33.3)
14 (28)
0.340
LMWH,
n
(%)
43 (50)
16 (44.4)
27 (54)
0.265
Statin,
n
(%)
18 (20.9)
8 (22.2)
10 (20)
0.354
ACEI,
n
(%)
32 (37.2)
14 (38.9)
18 (36)
0.469
ARB,
n
(%)
5 (5.8)
2 (5.5)
3 (6)
0.657
Mortality rate at 30 days’
follow up,
n
(%)
9 (10.4)
8 (22.2)
1 (2)
0.003
ASA, acetylsalicylic acid; LMWH, low-molecular-weight heparin; ACEI, angio-
tensin converting enzyme inhibitors; ARB, angiotensin receptor blocker.
Table 2.The laboratory parameters of the whole study group
Laboratory
parameters
Initial
Third day of
infusion
Two weeks after
infusion
p-
value
Glucose (mg/dl)
(mmol/l)
143.9
±
69.7
(7.99
±
3.87)
135.65
±
49.39
(7.53
±
2.74)
141.55
±
66.2
(7.86
±
3.67)
0.062
*
0.289
§
BUN (mg/dl)
23.6
±
13.7
30.0
±
20.7
24.9
±
13.5 0.014
*
0.458
§
Creatinine (mg/dl)
(μmol/l)
1.15
±
0.60
(101.66
±
53.04)
1.53
±
0.12
(135.25
±
10.61)
1.46
±
0.10
(129.06
±
8.84)
0.001
*
0.001
§
Haemoglobin (g/dl)
12.7
±
2.1
11.8
±
1.9
11.7
±
1.6 0.236
*§
Sodium (mmol/l)
134.9
±
14.8 137.4
±
4.9
137.1
±
15.7 0.228
*
0.117
§
Potassium (mmol/l)
4.76
±
0.78
4.11
±
0.68
4.42
±
0.92 0.406
*
0.606
§
Phosphorus
(mg/dl)
3.45
±
0.78
3.80
±
2.18
3.87
±
1.38 0.865
*
0.185
§
Calcium (mg/dl)
8.9
±
0.6
8.8
±
0.8
8.9
±
1.4 0.307
*
0.587
§
Albumin (g/dl)
3.6
±
0.7
3.4
±
0.8
3.2
±
0.7 0.339
*
0.047
§
CRP (mg/dl)
52.48
±
4.85 81.12
±
4.67
67.05
±
5.15 0.009
*
0.125
§
Urinary output
(cm
3
/24 h)
1545.17
±
873.00 1813.30
±
1123.46 1447.32
±
934.63 0.012
*
0.406
§
eGFR (MDRD)
(ml/min/1.73 m
2
)
76.98
±
35.57 71.16
±
43.43 72.84
±
53.39 0.01
*
0.04
§
Systolic blood pres-
sure (mmHg)
122.97
±
16.51 118.16
±
26.41 121.71
±
19.72 0.606
*
0.117
§
Diastolic blood
pressure (mmHg)
74.37
±
9.09 70.29
±
14.94 71.20
±
12.65 0.011
*
0.025
§
Mean arterial pres-
sure (mmHg)
90.57
±
10.5 86.25
±
17.9
88.04
±
14.3 0.024
*
0.112
*
p
-value for initial vs at the third day of infusion;
§
p-value for initial vs two weeks
after infusion.
BUN, blood urea nitrogen; CRP, C-reactive protein; eGFR, estimated glomerular
filtration rate.