ORIGINAL ARTICLE
DOI:10.5301/JN.2010.6259
Aspirin resistance in patients with chronic
renal failure
Azra Meryem Tanrikulu 1, Beste Ozben 1,
Mehmet Koc 2, Nurdan Papila-Topal 1,
Tomris Ozben 3, Oguz Caymaz 1
Abstract
Background: Chronic renal failure (CRF) is associated
with increased risk of cardiovascular morbidity and
mortality. Aspirin resistance worsens clinical progno-
sis. The aim of this study was to explore the preva-
lence of aspirin resistance in CRF.
Methods: Two hundred and forty-five CRF patients
(115 patients undergoing chronic hemodialysis and
130 patients with stage 3-4 chronic kidney disease
[CKD]) and 130 patients with normal renal functions
(control group) were consecutively recruited. All sub-
jects were taking aspirin regularly. Aspirin responsive-
ness was determined by Ultegra Rapid Platelet Func-
tion Assay-ASA (VerifyNow Aspirin). Aspirin resistance
was defined as aspirin reaction unit (ARU) 550.
Results: Aspirin resistance was detected in 53 patients
undergoing hemodialysis, 32 patients with stage 3-4
CKD and 22 controls. The frequency of aspirin re-
sistance was significantly higher in the CRF group
compared with controls (34.7% vs. 16.9%, p<0.001)
and in hemodialysis patients (46.1%) compared with
stage 3-4 CKD patients (24.6%, p<0.001) and con-
trols (16.9%, p<0.001). Multivariate analysis revealed
female sex (odds ratio [OR] = 2.201; 95% confidence
interval [95% CI], 1.173-4.129; p=0.014), hemodialysis
(OR=3.636; 95%CI, 1.313-10.066; p=0.013) and HDL
cholesterol (OR=0.974; 95% CI, 0.950-0.999; p=0.043)
as independent predictors of aspirin resistance in this
cohort of patients.
Conclusion: Patients with CRF have higher frequency
of aspirin resistance. This might further increase the
risk of cardiovascular morbidity and mortality in these
patients.
Key words: Aspirin, Aspirin resistance, Chronic kidney
disease, Chronic renal failure, Hemodialysis
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Department of Cardiology, Marmara University Faculty of
1
Medicine, Istanbul - Turkey
Division of Nephrology, Department of Internal Medicine,
2
Marmara University Faculty of Medicine, Istanbul - Turkey
Department of Biochemistry, Akdeniz University Faculty
3
1
1
1
of Medicine, Antalya - Turkey
Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey
Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey
Department of Cardiology, Marmara University Faculty of Medicine, Istanbul - Turkey
Introduction
Aspirin is an effective antiplatelet agent, exhibiting its ac-
tion by irreversibly inhibiting platelet cyclooxygenase-1
enzyme, thus preventing the production of thromboxane
A2 (TXA2). It has been used in the primary and second-
ary prevention of thromboembolic vascular events (1-3).
Yet, some patients have recurrent vascular events despite
long-term aspirin therapy, raising the possibility that they
are resistant to aspirin. The term resistance has been used
to describe the inability of aspirin to produce a measurable
response on ex vivo tests of platelet function, to inhibit
TXA2 biosynthesis in vivo or to protect individual patients
from recurrent thrombotic complications (4). Estimates of
the prevalence of aspirin resistance vary widely (5.5% to
60%), reflecting the diversity of various laboratory assays
and confounding from the broad range of disease states
investigated (5-8). Possible causes of aspirin resistance
include poor compliance or inadequate dose (9, 10), re-
duced bioavailability (11), increased platelet turnover,
up-regulation of non-platelet pathways of thromboxane
production (12, 13), drug interactions (14, 15) and genetic
variability (16-20). Despite ongoing research, there is cur-
rently no standardized approach to the diagnosis and no
proven effective treatment for aspirin resistance.
Chronic renal failure (CRF) is associated with high car-
diovascular morbidity and mortality (21). In patients with
end-stage chronic kidney disease (CKD) and undergoing
hemodialysis, coronary artery disease (CAD) incidence is
nearly 40%, and half of the mortality in these patients is
associated with cardiovascular diseases (22). Thus aspirin
use is important in these patients. Although aspirin resis-
tance has been well demonstrated in cardiovascular dis-
orders including CAD (12, 23), heart failure (24), cerebro-
vascular disease (25, 26), metabolic syndrome (27) and

diabetes (28-30), little is known about aspirin response
and its prognostic value in patients with CRF. The aim of
this study was to assess the prevalence of aspirin resis-
tance in patients with CRF.
Subjects and methods
The investigation complies with the principles outlined in the
Declaration of Helsinki. The study was approved by the local
ethics committee, and all participants gave written informed
consent before participating.
One hundred and fifteen patients undergoing chronic he-
modialysis and 130 patients with stage 3-4 CKD were
consecutively included into the study as the CRF group.
All stage 3-4 CKD patients had stage 3 or 4 CKD with or
without underlying morphological renal disease such as
diabetic nephropathy, hypertensive nephropathy, chronic
glomerulonephritis or polycystic kidney disease, and had
an estimated glomerular filtration rate (GFR) between 15
and 60 ml/min per 1.73 m2 for at least 6 months on 2 differ-
ent measurements. Estimated GFR was calculated using
the Modification of Diet in Renal Disease Study formula
(31). The patients undergoing chronic hemodialysis had
creatinine clearance below 10 ml/min per 1.73 m2 and had
been on chronic hemodialysis treatment for more than 6
months. They were dialyzed 3 times a week with polysul-
fone low-flux dialyzers (Fresenius Medical Care, Lexing-
ton, MA, USA). All hemodialysis patients underwent he-
modialysis for 4 hours by cannulation of the arteriovenous
fistula, and using sterile bicarbonate concentrate, heparin
and reverse osmosis water. Dialysate and blood flow rates
were 500 and 350 ml/min. Anticoagulation was performed
with heparin given as an intravenous bolus of 2,000 IU just
before hemodialysis followed by a continuous infusion at
a rate of 1,000 IU/hour.
The control group included 130 consecutive patients with
normal renal functions, estimated GFR 90 ml/min per 1.73
m2 and no underlying morphological renal disease.
All study subjects were taking aspirin 100 to 300 mg/
day regularly for at least 1 week. Compliance with aspirin
treatment was ascertained by a personal interview at the
time of inclusion to the study. A questionnaire on smoking
habits, clinical history of CAD, diabetes, hyperlipidemia,
hypertension and renal failure was carried out. Weight
and height were measured to determine body mass index
(BMI). Fasting blood samples were obtained to determine
blood glucose, creatinine, blood urea nitrogen, triglyc-
erides, high-density lipoprotein (HDL) cholesterol, low-
density lipoprotein (LDL) cholesterol, C-reactive protein,
hematocrit and platelet counts.
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Exclusion criteria included ingestion of ticlopidine, clopi-
dogrel, cilostazol, dipyridamole, abciximab, tirofiban or
antiinflammatory drugs for the last 10 days. Patients with
stage 2 CKD (patients with underlying morphological renal
disease and GFR between 60 and 89 ml/min per 1.73 m2)
or a history of major cardiovascular event within the past
3 months were also excluded.
Assessment of aspirin resistance with Ultegra
Rapid Platelet Function Assay
From every patient 2-mL blood samples were drawn into
tubes containing 3.2% citrate 1 to 4 hours after aspirin
intake. Blood samples of the hemodialysis patients were
obtained on the second hemodialysis session of the week
before the hemodialysis session began. Aspirin-induced
platelet inhibition was measured using a commercially
available point-of-care assay, the Ultegra Rapid Platelet
Function Assay-ASA (VerifyNow System; Accumetrics, San
Diego, CA, USA). This is a whole blood optical detection
system that measures agonist-induced platelet aggregation
using cationic propyl gallate to activate platelets. Platelet
function measurement is based on the ability of activated
platelets to bind fibrinogen. The instrument measures the
change in optical signal caused by aggregation. If aspirin
has produced the expected antiplatelet effect, fibrinogen-
coated beads will not agglutinate, and light transmission
will not increase. The results are reported as aspirin reac-
tion units (ARUs). The cutoff point is set as 550 ARU ac-
cording to the manufacturers clinical studies using optical
aggregometry as the comparison standard. An ARU 550
indicates absence of aspirin-induced platelet dysfunction
and is defined as aspirin-resistant. An ARU <550 indi-
cates platelet dysfunction consistent with aspirin has been
detected and is defined as aspirin-sensitive (32).
Statistical analysis
All statistical tests were performed with a commercially avail-
able statistical analysis program (SPSS 11.0 for Windows).
Continuous variables were expressed as means standard
deviation, while categorical variables were expressed as
ratios. Students t-test and the Mann-Whitney U-test were
used for comparison of parametric and nonparametric vari-
ables between 2 groups, while ANOVA and Kruskal-Wallis
tests were used for comparison of parametric and nonpara-
metric variables among 3 groups. Categorical variables were
compared using the chi-square test. Pearsons correlation
was used for univariate analysis. A logistic regression analy-
sis was modeled to determine the independent predictors of
637
Tanrikulu et al: Aspirin resistance and renal failure
aspirin resistance in this cohort of patients. A p value <0.05
was interpreted as statistically significant.
Results
Patient characteristics
All patients were included in the study consecutively
among patients taking regular aspirin. The CRF group
consisted of 115 patients undergoing chronic hemodialy-
sis and 130 patients with stage 3-4 CKD. The mean Kt/V
(urea kinetics, postdialysis volume) and urea reduction ra-
tio (URR) values of the hemodialysis patients were 1.30
0.43 and 69% 7%, respectively. The mean GFR of the
stage 3-4 CKD patients was 38 14 ml/min per 1.73 m2.
The control group consisted of 130 patients with mean
GFR of 98 6 ml/min per 1.73 m2.
The general characteristics and laboratory parameters of
the CRF group and controls are listed in Table I. There
were no significant differences in sex and age distri-
bution between the whole CRF group and controls, al-
though sex and age distributions differed when the CRF
group was subgrouped as hemodialysis and stage 3-4
CKD groups. There were statistically significant differ-
ences in the frequency of hypertension, BMI and levels
of creatinine, LDL cholesterol, HDL cholesterol, triglyc-
erides, hematocrit and platelet counts between the CRF
group and controls.
Aspirin resistance in CRF patients and controls
Aspirin resistance was detected in 85 CRF patients (in 53
patients undergoing chronic hemodialysis and in 32 pa-
tients with stage 3-4 CKD) and 22 control patients (Tab.
II). The frequency of aspirin resistance was significantly
higher in the CRF group compared with the control group
(34.7% vs. 16.9%; p<0.001; odds ratio [OR] = 2.608;
95% confidence interval [95% CI], 1.537-4.424) and in
patients undergoing chronic hemodialysis compared
with stage 3-4 CKD patients (46.1% vs. 24.6%; p<0.001;
OR=2.618; 95% CI, 1.523-4.501) and controls (46.1%
vs. 16.9%; p<0.001; OR=4.196; 95% CI, 2.333-7.548).
The frequency of aspirin resistance was higher in stage
3-4 CKD patients compared with controls, but the dif-
ference was not significant (24.6% vs. 16.9%; p=0.126;
OR=1.603; 95% CI, 0.873-2.944).
The CRF group had significantly higher aspirin reaction
units than the control group (511 76 ARU vs. 479
72 ARU, p<0.001). The duration of aspirin therapy and
638 2011 Societ Italiana di Nefrologia - ISSN 1121-8428
the median aspirin doses were similar between the CRF
group and controls.
Characteristics of aspirin-resistant and aspirin-
sensitive patients
The general characteristics and laboratory parameters of
aspirin-resistant and aspirin-sensitive patients are shown in
Table III. The frequencies of female sex, CRF and hemodi-
alysis were significantly higher in the aspirin-resistant pa-
tients. Daily aspirin doses and duration of aspirin therapy
were similar between the aspirin-resistant and aspirin-sensi-
tive patients. Among the laboratory parameters, blood urea
nitrogen and creatinine levels were significantly higher, while
hematocrit levels and platelet counts were significantly low-
er in the aspirin-resistant patients.
Relations between aspirin resistance and differ-
ent variables
Aspirin reaction units were correlating positively with serum
creatinine levels (p<0.001, r=0.324) and negatively with esti-
mated GFR (p<0.001, r=0.337). An increase of 1 mg/dL in
creatinine levels showed a 10% increase in the odds of hav-
ing aspirin resistance (p=0.001; 95% CI, 4.1%-16.3%) while
an increase of 1 ml/min per 1.73 m2 in GFR showed a 1.1%
decrease in the odds of having aspirin resistance (p=0.001;
95% CI, 0.5%-1.7%).
There was a significant relation between aspirin resistance
and sex of patient. Among the aspirin-resistant patients,
the percentage of women was 53.3%, while only 40.7% of
aspirin-sensitive patients were women (p=0.027; OR=1.663;
95% CI, 1.059-2.611). There were no significant associa-
tions between aspirin resistance and age, hypertension, dia-
betes, hyperlipidemia, CAD or smoking.
No significant correlation was found between aspirin
reaction units and aspirin daily doses, duration of as-
pirin therapy, BMI, systolic or diastolic blood pressure,
blood glucose, LDL cholesterol or triglyceride levels.
However, aspirin reaction units were significantly corre-
lating with HDL cholesterol (p<0.001, r=0.212), hema-
tocrit (p<0.001, r=0.271) and platelet levels (p<0.001,
r=0.237).
We modeled a logistic regression analysis to determine
the independent predictors of aspirin resistance in this
cohort of patients. Multivariate analysis for predictors of
aspirin resistance is presented in Table IV. Multivariate
analysis revealed that female sex (OR=2.201; 95% CI,
1.173-4.129; p=0.014), hemodialysis (OR=3.636; 95% CI,
1.313-10.066; p=0.013) and HDL cholesterol (OR=0.974;
 JNEPHROL 2011; 24 ( 05 ) : 636-646

TABLE I
GENERAL CHARACTERISTICS AND LABORATORY PARAMETERS OF CHRONIC RENAL FAILURE GROUP AND CONTROLS

Chronic renal failure group

(n=245)
Control group p Value*
(n=130)

Hemodialysis (n=115) Stage 3-4 CKD (n=130)

64.4 14.1 NS
Age (years) 64.7 12.4
58.3 14.0 69.7 11.8 <0.001a,b,c

105/140 NS
Sex, female/male 61/69
60/55 45/85 0.017d,e

79.2 0.032
Hypertension (%) 69.2
67.8 89.2 <0.001a,f

43.3 NS
Hyperlipidemia (%) 41.5
27.8 56.9 <0.001a,g,e

33.9 NS
Diabetes mellitus (%) 32.3
29.6 37.7 NS

36.2 NS
Coronary artery disease (%) 31.5
20.9 50.0 <0.001a,c

31.8 NS
Smoking (%) 40.0
27.0 36.2 NS
26.3 5.4 0.037
Body mass index (calculated as kg/m2) 27.5 4.6
25.0 5.9 27.3 4.9 <0.001a,b
131 24 NS
Systolic blood pressure (mm Hg) 129 20
127 23 135 24 0.011d
76 14 NS
Diastolic blood pressure (mm Hg) 76 12
76 12 77 16 NS
82 16 NS
Heart beat (/min) 78 15
83 16 80 16 0.024g
120 54 NS
Glucose (mg/dL) 122 45
119 55 120 52 NS
79 58 <0.001
Blood urea nitrogen (mg/dL) 19 7
122 55 41 21 <0.001a,b,f
to be continued
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Tanrikulu et al: Aspirin resistance and renal failure

TABLE I
CONTINUED

Chronic renal failure group

(n=245)
Control group p Value*
(n=130)
Hemodialysis (n=115) Stage 3-4 CKD (n=130)

5.4 4.9 <0.001

Creatinine (mg/dL) 0.8 0.2
9.2 4.7 1.9 0.9 <0.001a,b,c

18.8 31.5 NS
C-reactive protein (mg/L) 22.6 48.7
16.0 22.9 22.7 40.6 NS
39 12 0.001
HDL cholesterol (mg/dL) 44 15
35 10 43 12 <0.001a,b
102 41 0.009
LDL cholesterol (mg/dL) 113 35
95 31 108 47 0.001h,i

158 104 0.006

Triglycerides (mg/dL) 128 67
172 105 145 101 0.002i

35.9 8.9 <0.001

Hematocrit (%) 40.4 4.7
33.0 4.6 38.5 10.8 <0.001a,b

223 101 <0.001

Platelets (103/mm3) 261 71
184 61 258 116 <0.001a,b

CKD = chronic kidney disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NS = not significant.
*p values in the upper cell in each row show comparison of all 245 chronic renal failure patients with controls, while p values
in the lower cell in each row show ANOVA, Kruskal-Wallis or chi-square test comparing hemodialysis patients, stage 3-4 CKD
patients and controls.
Post hoc analysis:
ap<0.001, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
bp<0.001, patients undergoing chronic hemodialysis vs. controls.
cp<0.01, stage 3-4 CKD patients vs. controls.
dp<0.01, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
e
p<0.05, stage 3-4 CKD patients vs. controls.
f
p<0.001, stage 3-4 CKD patients vs. controls.
g
p<0.05, patients undergoing chronic hemodialysis vs. controls.
h
p<0.05, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
p<0.01, patients undergoing chronic hemodialysis vs. controls.
i

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 JNEPHROL 2011; 24 ( 05 ) : 636-646

95% CI, 0.950-0.999; p=0.043) were independent pre-
dictors of aspirin resistance in this cohort of patients.
Discussion
Aspirin resistance has been considered a multifactorial
phenomenon underlying factors ranging from nonadher-
ence of patients to antiplatelet therapy to demographic
characteristics, acute coronary syndromes as well as ge-
netic polymorphisms involving platelet glycoproteins and
cytochrome P450 isoenzymes (33). Although a recent
study (34) suggested that aspirin therapy might improve
renal outcome after acute renal failure, renal failure itself
may play a role in the development of resistance to aspirin
therapy, and aspirin resistance, in turn, may worsen the
prognosis of patients with CKD. Actually, renal failure was
included as a comorbidity associated with aspirin resis-
tance in a review (33). However, Gum et al (35) reported
that the presence of renal disease caused no difference in
aspirin sensitivity in patients with cardiovascular disease.
A recent meta-analysis has reported that aspirin resis-
tance might be higher in patients with previous renal im-
pairment, and recommended future studies exploring the
relation of aspirin resistance with renal failure (36). How-
ever, no study to date has been designed to evaluate the
incidence of aspirin resistance in patients with CKD.
In our study, we assessed aspirin resistance in 245 pa-
tients with CRF and found that 85 patients (53 patients
undergoing hemodialysis and 32 patients with stage 3-4
CKD) had aspirin resistance. The frequency of aspirin
resistance was significantly higher in CRF patients com-
pared with the controls, especially in patients undergoing
chronic hemodialysis. Multivariate analysis of our data fur-
ther confirmed hemodialysis as an independent predictor

TABLE II
FREQUENCY OF ASPIRIN RESISTANCE IN PATIENTS WITH CHRONIC RENAL FAILURE AND CONTROLS

Chronic renal failure group

(n=245)
Control group p Value*
(n=130)
Hemodialysis (n=115) Stage 3-4 CKD (n=130)

85 (34.7) <0.001
Aspirin resistance, no. (%) 22 (16.9)
53 (46.1) 32 (24.6) <0.001a,b

511 76 <0.001
Aspirin reaction unit, ARU 479 72
549 60 478 74 <0.001a,b

100 NS
Median aspirin dose, mg/day 100
100 100 NS

27 42 NS
Aspirin duration, months 36 67
18 29 35 50 0.009c,d

CKD = chronic kidney disease; NS = not significant.

*p values in the upper cell in each row show comparison of all 245 chronic renal failure patients with controls, while p values in
the lower cell in each row show ANOVA test or chi-square test comparing hemodialysis patients, stage 3-4 CKD patients and
controls.
Post hoc analysis:
a
p<0.001, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
b
p<0.001, patients undergoing chronic hemodialysis vs. controls.
c
p<0.05, patients undergoing chronic hemodialysis vs. stage 3-4 CKD patients.
p<0.05, patients undergoing chronic hemodialysis vs. controls.
d

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Tanrikulu et al: Aspirin resistance and renal failure

of aspirin resistance in our study. Although the stage 3-4 clinical significance. These findings suggest the possibil-
CKD patients had an increased risk of aspirin resistance ity of an association between aspirin resistance and renal
compared with the controls, the difference did not reach functions. We found that an increase of 1 mg/dL in creati-

TABLE III
CHARACTERISTICS AND LABORATORY PARAMETERS OF ASPIRIN-RESISTANT AND ASPIRIN-SENSITIVE PATIENTS

Aspirin-resistant patients Aspirin-sensitive patients

p Value
(n=107) (n=268)

Age (years) 63.9 13.2 64.7 13.6 NS

Sex (female/male) 57/50 109/159 0.027

Chronic renal failure (%) 79.4 59.7 <0.001

Hemodialysis (%) 49.5 23.1 <0.001

Hypertension (%) 74.8 76.1 NS

Hyperlipidemia (%) 39.3 44.0 NS

Diabetes (%) 38.3 31.3 NS

Coronary artery disease (%) 33.6 34.7 NS

Smoking (%) 33.6 35.1 NS

Body mass index (calculated as kg/m2) 26.5 5.0 26.8 5.2 NS

Systolic blood pressure (mm Hg) 130 24 131 22 NS

Diastolic blood pressure (mm Hg) 76 12 76 14 NS

Heart beat (/min) 81 16 80 16 NS

Mean aspirin dose (mg/day) 151.9 86.9 160.6 91.5 NS

Aspirin duration (months) 27 47 31 54 NS

Glucose (mg/dL) 121 56 120 49 NS

Blood urea nitrogen (mg/dL) 79 63 50 48 <0.001

Creatinine (mg/dL) 5.1 4.2 3.3 4.5 <0.001

C-reactive protein (mg/L) 20.1 30.9 19.8 40.2 NS

Total cholesterol (mg/dL) 171 50 179 46 NS

LDL cholesterol (mg/dL) 103 42 107 38 NS

Triglycerides (mg/dL) 147 91 148 95 NS

Hematocrit (%) 35.8 6.5 38.1 8.4 0.012

Platelets (103/mm3) 214 75 245 99 0.004

HDL = high-density lipoprotein; LDL = low-density lipoprotein; NS = not significant.

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 JNEPHROL 2011; 24 ( 05 ) : 636-646

nine levels showed a 10% increase in the odds of having
aspirin resistance, while an increase of 1 ml/min per 1.73
m2 in GFR showed a 1.1% decrease in the odds of hav-
ing aspirin resistance. Similarly, Acikel et al (37) detected
aspirin resistance in 27.5% of renal transplant recipients
and found that the incidence of aspirin resistance was
higher among patients with GFR <60 ml/min compared
with those with a GFR 60 ml/min.
Aspirin resistance may be associated with increased
inflammation and oxidative stress (38, 39). Arachidonic
acid derivative isoprostanes exhibit potent vasoconstric-
tor and proaggregatory effects similar to that of TXA2.
Increased oxidative stress may increase plasma isopros-
tane levels, and increased cyclooxygenase-independent
isoprostane formation in platelets might contribute to
aspirin resistance (40). There is evidence of increased
oxidative stress and acute-phase inflammation in pa-
tients with CRF compared with healthy subjects (41).
Inflammation-induced activation of cyclooxygenase-2
leading to TXA2 synthesis and oxidative stress lead-
ing to production of thromboxane A2 through pathways
not blocked by aspirin might contribute to the develop-
ment of aspirin resistance in patients with CRF. Oxidative
stress and disturbances in antioxidant enzymes occur at
the early stages of chronic uremia and are exacerbated
by hemodialysis (42). A few studies indicated an inverse
correlation of oxidative stress biomarkers with estimated
GFR (43). This may explain the higher incidence of aspi-
rin resistance in patients undergoing hemodialysis. In our
study, C-reactive protein levels were similar between the
aspirin-resistant and aspirin-sensitive patients, which
raised doubts about the possible role of inflammation in
aspirin resistance. This finding might be explained by the
small size of the study groups and also by the multifacto-
rial nature of aspirin resistance. We did not study oxida-
tive stress markers or plasma isoprostane levels obvi-
ously another study limitation which might be useful
in understanding the mechanism of aspirin resistance in
patients with CKD.
In our study, the percentage of women was significantly
higher in aspirin-resistant patients. Multivariate analysis
also revealed female sex as an independent predictor

TABLE IV
MULTIVARIATE ANALYSIS FOR PREDICTORS OF ASPIRIN RESISTANCE

Variable Odds ratio 95% Confidence interval p Value

Age 1.010 0.987-1.034 0.395

Female sex 2.201 1.173-4.129 0.014
Chronic Renal failure 2.512 0.937-6.737 0.067
Hemodialysis 3.636 1.313-10.066 0.013
Hypertension 1.113 0.561-2.210 0.759
Diabetes 1.772 0.894-3.510 0.101
Hyperlipidemia 0.957 0.487-1.882 0.899
Coronary artery disease 1.255 0.663-2.376 0.485
Smoking 1.980 0.985-3.752 0.052
Glucose 1.000 0.994-1.007 0.901
Creatinine 1.009 0.997-1.022 0.144
Triglycerides 0.997 0.994-1.001 0.136
HDL cholesterol 0.974 0.950-0.999 0.043
Hematocrit 0.983 0.938-1.031 0.486
Platelets 1.000 0.998-1.003 0.263

HDL = high-density lipoprotein.

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Tanrikulu et al: Aspirin resistance and renal failure
of aspirin resistance in our study. This is in accordance
with other studies showing higher incidence of aspirin
resistance in females (32, 35, 44-46).
Although we did not find any significant association be-
tween aspirin resistance and hyperlipidemia, aspirin re-
action units significantly correlated with HDL cholesterol,
and multivariate analysis revealed HDL cholesterol as an
independent predictor of aspirin resistance. Watala et
al (47) found that the reduced response of platelets to
aspirin in diabetic subjects was associated with lower
concentration of HDL cholesterol. They suggested that
HDL cholesterol might be regarded a factorial compo-
nent of a cluster of lipid variables related to platelet re-
activity, and their sensitivity to antiplatelet agents and
the prophylactic HDL action might be deduced from its
antiatherogenic properties.
Conclusion
We found increased aspirin resistance in patients with
CRF, especially in patients undergoing chronic hemodi-
alysis. Aspirin resistance might increase the cardiovascu-
lar morbidity and mortality in CRF patients, who are al-
ready at increased risk for cardiovascular complications.
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644 2011 Societ Italiana di Nefrologia - ISSN 1121-8428
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The study was presented at the ESC Congress 2010, Stockholm,
Sweden (accepted as poster presentation).
Financial support: This study is supported by both Marmara
University and Akdeniz University research funds (no grant number
is applicable).
Conflict of interest statement: None declared.
Address for Correspondence:
Beste Ozben
Yildiz Caddesi Konak Apartmani
No. 43/24 Besiktas
34353 Istanbul, Turkey
bestes@doctor.com,
besteozben@yahoo.com
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Accepted: October 25, 2010