Sunday, July 16, 2006
blood volume, a new mathematical model of intra-HFR fluid and solutes
kinetics, bicompartimental for urea and sodium and tricompartimental for
fluids, including the kinetic of buffers and equivalent masses, has been
set up.The aim of our study has been the sperimental validation of this
mathematical model for Profiler-HFR.
Methods: For this field the curves of plasma urea, sodium, potassium,
osmolarity and of blood volume variation % (BV%) elaborated “a priori” by
the model have been compared with those determined “in vivo” during the
course of Profiled-HFR sessions. “In vivo” data have been collected during
20 Profiler-HFR sessions made in 10 patients, two sessions per patient
(age 65±15 years, body weight 79±5,3 kgs, systolic arterial pressure
101±6 mmHg). During each session, 4 hour duration, plasma urea, sodium,
potassium and osmolarity have been evaluated at time 0’, 30’, 60’, 90’,
120’, 150’, 180’, 210’, 240’; BV% (Transonic System) every 30’.
Results: The comparation between the curves predicted by the model
and those determined “in vivo” showed a good “fitting”: for sodium and
potassium mean differences resulted lower then the standard error of the
method of dosage (respectively ±1,8 and ±0,2 mEq/L), the same for urea
and osmolarity (respectively ±0,3 g/L and ±4,3 mOsm/L); also a difference
statistically not significative emerged between curves of BV%.
Conclusions: The analysis of results demonstrated that the mathematical
model for Profiler-HFR, predicting correctly solutes and fluid kinetics, is
able to elaborate “a priori” sodium and UF profiles, for HFR, aimed to
the stabilization of intradialytic blood volume and blood pressure. Profiler-
HFR, with an, “a priori”, automatic elaboration of profiles similar to that of
Profiler-HD, will be indicated in patients affected by MIA syndrome and
intradialytic symptomatic hypotension.
SP493 EFFECTS OF PROFILER-HD ON DIALYSIS INTOLERANCE:
RESULTS OF A MULTICENTRIC ITALIAN STUDY
Luigi Coli , Mauro Aloisi 2 , Mauro Atti 3 , Cristian Bergamini 3 ,
1
Alessandro Balducci 2 , Roberto Bellazzi 2 , Francesco Cecchini 2 ,
Luciano Cristinelli 2 , Salvatore Di Filippo 2 , Giancarlo Marinangeli 2 ,
Massimo Morosetti 2 , Francesco Quarello 2 , Mauro Sasdelli 2 ,
Carmine Stallone 2 , Maurizio Tancredi 2 , Renzo Tarchini 2 , Sergio Stefoni 1 .
1 (MC-FAN) that makes it possible to directly observe the flow of blood cell
Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University
Hospital, Bologna, Italy; 2 Nephrology and Dialysis Units, Arezzo, Atri,
Giulianova, Lecco, Mantova, Ostia, Pesaro, Piacenza, Ravenna, Roma, S.
Giovanni R, Torino, Viareggio, Vigevano, Italy; 3 Bellco, Mirandola, Italy
Introduction and Aims: Profiler-HD is a dialysis technique based on the use
of dialysate sodium and UF profiles and clinically effective on hypotension
and other symptoms of dialysis intolerance. For the automatic elaboration
of individual patient sodium and UF profiles, aimed to the stabilization
of intradialytic plasma osmolarity and blood volume, Profiler-HD uses a
new mathematical model of intradialytic fluids, solutes and buffer kinetics,
implemented into the Bellco Formula 2000 Plus machine.Aim of the study:
determine the efficacy of 6 month Profiler-HD treatment on intradialytic
hypotension and on other dialysis intolerance symptoms.
Methods: For this field, 55 dialysis patients, selected among those on chronic
dialysis in 15 Italian Dialysis Centres (age 61±11 years, dialysis age 53±18
months, M/F = 24/31), were included in the study. Inclusion criteria: the
intradialytic appearance, during the previous basal treatment with constant
dialysate sodium and UF, of hypotension and/or symptomatic events
(cramps, headache, nausea, other). Two treatment periods were considered:
the last month on the basal treatment vs the 6 month Profiler-HD treatment
period. During the two periods (each patient control of him/herself) were
made the following evaluations: intradialytic systolic blood pressure (SBP)
and diastolic, heart rate, % of intradialytic hypotension and/or symptomatic
events, intradialytic blood volume variation % (Transonic System), dry
body weight, interdialytic body weight gain, dialysis sodium mass balance,
electrolyte balance.
Results: Results (basal vs Profiler-HD period): mean pre-session SBP from
113±27 to 119±21 mmHg (p=ns); mean intradialytic SBP from 96±12
to 118±16 mmHg (p<0.05). On last month basal treatment 71±11% of
all sessions were symptomatic (hypotension or symptomatic events) vs
12±18% of all sessions of 6 months Profiler (p<0.001). The behaviour of
other parameters was: dry body weight from 70.2±11.9 to 69.3±12.6 kgs
(p=ns); mean body weight gain from 3.0±0.7 to 3.1±0.8 kgs (p=ns). Pre-
Dialysis – Cardiovascular risk 1 iv181
session sodiemia from 136.8±3.0 to 136.8±1.7 mEq/l (p=ns) and kaliemia
from 5.3±0.7 to 5.4±0.6 mEq/l (p=ns).
Conclusions: The analysis of results demonstrated that Profiler-HD allowed
to obtain a significant reduction of intradialytic events as respect previous
basal treatment, with associated higher mean SBP during sessions and
without the appearance of clinical signs of sodium/fluid overload (stable
pre-session SBP, dry body weight, body weight gain).
In conclusion, Profiler-HD induced an improvement of dialysis clinical
tolerance in patients prone to hypotension or to other intradialytic symptoms.
Dialysis – Cardiovascular risk 1
SP494 INCREASED LEUKOCYTE AGGREGATE ARE
ASSOCIATED WITH ATHEROSCLEROSIS IN PATIENTS
WITH HEMODIALYSIS
Shuzo Kobayashi, Machiko Oka, Tsutomu Mano, Ryota Ikee,
Hidekazu Moriya, Takayasu Ohtake. Nephrology and Kidney & Dialysis
Center, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
Introduction and Aims: In an initial step of atherosclerosis, on endothelial
cells platelet-monocyte complex produces various cytokines, which lead
to an micro-inflammation.The formation of leukocyte aggregates (LA),
particularly platelet-leukocyte aggregates during HD may play an important
pathophysiological role by facilitating platelet-endothelial interaction. How-
ever, little data is available concerning a role of blood rheology, particularly,
platelet-leukocyte interactions, in patients with hemodialysis (HD).
Methods: We investigated a relationship between leukocyte aggregates
(LA) and atherosclerosis in 118 patients with HD. Biomarkers such as
high-sensitive c-reactive protein (hsCRP), osteopontin (OPN), monocyte
chemoattractant protein-1 (MCP-1), fibrinogen and as surrogate markers
of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave
velocity (baPWV) or carotid intima-media thickness (IMT) were studied.
As an assessment of LA, a new method, micro-channel array flow analyzer
elements through the micro-channel, was used. In this system, we measured
a number of LA during 50 μl –flow of whole blood through micro-channels.
To identify which leukocyte (monocytes, neutrophil, lymphocytes) are
conjugated with platelets, flow cytometry was performed.
Results: In healthy individuals, a number of LA during 50 μl –flow of whole
blood was 23.4±9.8, whereas in HD patients it was 48.2±16.4 (P<0.001).
Flow cytometry demonstrated that in monocytes, 16.9% of total monocytes
were aggregated with platelets, in neutrophil 8.5%, and in lymphocytes
3.3%, respectively. LA was positively correlated with plasma levels of
fibrinogen (P<0.01), or serum hsCRP (P<0.01). Although there was no
association with serum osteopontin levels, LA had a tendency of association
with serum monocyte chemotractant protein-1(MCP-1)(P=0.07). Moreover,
LA had highly significant associations with baPWV(P<0.001) and carotid
intima-media thickness (P<0.001).
Conclusions: We demonstrated that leukocyte aggregates, which were
predominantly monocytes-platelets complex, increased in HD patients, and
there was a strong correlation between increased leukocyte aggregates and
atherosclerosis in HD patients.
SP495 A STRONG CORRELATION BETWEEN INFLAMMATION
AND THE PROGRESSION OF CORONARY ARTERY
CALCIFICATION IN PATIENTS WITH HEMODIALYSIS
Takayasu Ohtake, Machiko Oka, Tomoko Ishii, Kyoko Maesato,
Tsutomu Mano, Ryota Ikee, Hidekazu Moriya, Shuzo Kobayashi.
Nephrology, and Kidney & Dialysis Center, Shonan Kamakura General
Hospital, Kamakura, Kanagawa, Japan
Introduction and Aims: Coronary artery calcification (CAC) is an inde-
pendent risk factor for future cardiac events in the general population. In
patients with hemodialysis (HD), CAC is often found and may be markedly
progressed in some patients. However, the underlying mechanisms for the
progression of CAC have not been fully elucidated. We tried to elucidate
iv182 Dialysis – Cardiovascular risk 1
1) the factors which were associated with CAC and its progression, and 2)
whether CAC was correlated with peripheral artery diseases (PAD).
Methods: We prospectively evaluated CAC score by electron-beam com-
puted tomography (EBCT) in 75 outpatients (age 66.0±10.5 years old, HD
vintage 90.0±63.0 months) on stable maintenance HD therapy. Fifty-six
patients subsequently underwent follow-up EBCT (2nd EBCT) after 15
months for the evaluation of progression of CAC (CAC). Several param-
eters including serum high-sensitive C-reactive protein (hsCRP), Ca, Pi,
Ca×Pi product, plasma fibrinogen and body mass index (BMI) were evalu-
ated at the time of first EBCT. Surrogate markers including brachial-ankle
pulse wave velocity (baPWV), carotid intima-media thickness (IMT), and
ankle-brachial blood pressure index (ABI) were also evaluated. We verified
the correlation between these parameters and CAC. Moreover, independent
risk factors for CAC and its progression were also evaluated.
Results: CAC score of the first EBCT was significantly positively correlated
with hsCRP (r=0.268, p=0.01), fibrinogen (r=0.293, p=0.005), serum Ca
(r=0.217, p=0.031), HD vintage (r=0.321, p=0.0026), and baPWV (r=0.181,
p=0.013). Stepwise multiple regression analysis revealed that HD vintage
(standard regression coefficient β=0.321, p=0.0025) and hsCRP (β=0.266,
p=0.0025) were the independent risk factors for CAC. Although baPWV,
represented as a characteristic of aortic stiffness, was significantly associated
with CAC, ABI and IMT were not associated with CAC. On the other hand,
CAC was significantly positively correlated with serum Ca (r=0.226,
p=0.046), fibrinogen (r=0.278, p=0.018), hsCRP (r=0.398, p=0.0011), and
BMI (r=0.248, p=0.032). Multivariate analysis showed that only hsCRP was
an independent risk factor for the progression of CAC (β=0.413, p=0.0024).
Conclusions: These findings provide that chronic micro-inflammation, as
shown by hsCRP and fibrinogen, was strongly associated with CAC and its
progression in patients with HD.
SP496 ELEVATED PLATELET-DERIVED MICROPARTICLES
AFTER DIALYSIS SESSION AND EFFECT OF CILOSTAZOL
IN HAEMODIALYSIS PATIENTS
Ryoichi Nakazawa, Kazuko Motohashi, Nakanobu Azuma. Department of
Nephrology, Tokatsu Clinic Hospital, Matsudo, Chiba Prefecture, Japan
Introduction and Aims: Atherosclerosis is the major cause of death in
haemodialysis (HD) patients. Platelet-derived microparicles (PDMP) are
active molecules released from platelets and involved in the hemostatic
and infammatory responses. PDMP may contribute to the development of
atherosclerosis by modulation of monocyte-endothelial cell interactions.
However, at latest report by flow cytometric assay, the HD procedure did
not affect plasma PDMP levels. In this study we investigated the platelet
activity and the effect of an antiplatelet drug, a specific inhibitor of type 3
cAMP phosphodiesterase, cilostazol.
Methods: Fifty HD patients (27 males and 23 females, age 64.5 ± 7.9 years,
time on HD 11.1 ± 9.0 years) and 19 healthy subjects (group C; 3 males
and 16 females, age 31.1 ± 7.9 years) were enrolled in this study. These
HD patients were divided into 2 groups. Fifteen patients (group A; age 65.5
± 5.8 years, time on HD 10.3 ± 8.3 years) were treated with cilostazol
(50-200 mg/day) for various cardiovascular complications, while the other
35 patients (group B; age 64.1 ± 8.8 years, time on HD 11.4 ± 9.4 years)
without cilostazol. The dialyzers used were a polysulfone, a vitamin E-
modified polysulfone, a polymethylmethacrylate, and a ethylenevinylalcohol
dialyzer. Plasma PDMP levels were measured by using a newly developed
enzyme-linked immunosorbent assay (ELISA) method.
Results: Pre-HD plasma PDMP levels were not significantly different in 3
groups (A; 8.18 ± 6.17 U/mL, B; 5.88 ± 4.52 U/mL, C; 7.57 ± 2.22 U/mL).
Post-HD plasma PDMP levels were significantly increased compared with
pre-HD levels in both A and B groups (A; 11.78 ± 4.78 U/mL, p < 0.01,
B; 12.39 ± 5.62 U/mL, p < 0.01). An increasing ratio (post/pre HD plasma
PDMP levels) in the A gruop was significantly lower compared with that in
the B group (1.77 ± 0.52 v.s. 3.04 ± 2.33, p < 0.05). Flow cytomeric assays
for plasma PDMP are not sufficiently sensitive to count very small particles
accurately. The measurement of PDMP by ELISA seems to be superior to
flow cytometric detection.
Conclusions: These findings suggest that the HD procedure using heparin
affects PDMP counts and cilostazol is effective to reduce platelet activation.
Sunday, July 16, 2006
SP497 HOMOCYSTEINE-LOWERING THERAPY ATTENUATES
INFLAMMATION AND IMPROVES SERUM ALBUMIN
LEVELS IN NON-DIABETIC HEMODIALYSIS PATIENTS
Tzu-Yuan Chang 1 , Kang-Ju Chou 1 , Chin-Feng Tseng 2 , Kuo-Cheng Lu 2 .
1
Division of Nephrology, Department of Medicine, Kaohsiung Veterans
General Hospital, Kaohsiung, Taiwan; 2 Department of Medicine, Cardinal
Tien Hospital, Fu-Jen Catholic University, School of Medicine, Hsin-Tien
City, Taipei County, Taiwan
Introduction and Aims: Studies concerning the value of total plasma
homocysteine (tHcy) levels in predicting cardiovascular risk in end-stage
renal disease (ESRD) have shown conflicting results, with both high and
low levels suggesting a worse outcome. Recent investigations have found
that chronic in flammation is the main risk factor for cardiovascular disease
in patients with uremia. Folic acid and vitamin B administration lowers
tHcy levels and cardiovascular risk in the general population. In patients
on hemodialysis, such treatment also lowers tHcy levels but whether the
cardiovascular risk is lessened remains a big question. This prospective
study examines the effect of folic acid and vitamin B intake on levels of
serum homocysteine, inflammatory and nutritional markers in hemodialysis
patients with and without diabetes.
Methods: Folic acid, (5 mg/tab, 1 tab daily) and Vitamin B complex
(B1: 5 mg, B2: 3 mg, nicotinamide: 20mg, B6: 0.5mg, B12: 1mcg, calcium
pantothenate: 3mg; 1 capsule three times daily) were given for 3 consecutive
months to 61 patients (DM: 14, no DM: 44) on maintenance hemodialysis.
Before and after completion of three months of treatment, fasting pre-
hemodialysis blood samples were collected for measurements of tHcy,
high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), albumin,
cholesterol, hematocrit, Vitamin B12 and folate levels.
Results: After 3 months of treatment, tHcy (34.01±14.89 vs 22.01±10.55
umol/L, p<0.001) and hs-CRP (median with 25%-75% percentile: 0.599
with 0.211-1.105 vs. 0.347 with 0.141-0.579 mg/dL, P<0.001) levels were
significantly decreased. The observed reductions were significantly lower
in the non-diabetic patients (tHcy: 18.94±8.50 vs 29.53±11.36 umo;/L,
p<0.001 and hs-CRP: median with 25%-75% percentile: 0.576 with 0.207-
1.045 vs. 0.223 with 0.105-0.527 mg/dL, p<0.001) but this was not true
for the diabetic group. The rate of hs-CRP reduction was significantly
correlated with the rate of albumin elevation in non-diabetics (3.87±0.32
vs 4.16±0.34 g/dL, p<0.001, correlation coefficient: 0.548, P<0.001), but
the observed rates were not significant in the diabetic patients (correlation
coefficient: 0.0199, P=0.939). Levels of IL-6 were not changed significantly.
Conclusions: Folic acid and vitamin B administration significantly lowers
tHcy and CRP levels in non-diabetics on hemodialysis. Folic acid may be
cardioprotective partly by diminishing the level of inflammation in ESRD,
and attenuation of inflammation may help improve nutrition in such patients.
SP498 RISK FACTORS FOR DE NOVO ACUTE CORONARY
EVENTS IN PATIENTS INITIATING HEMODIALYSIS WITH
NO PREVIOUS CARDIAC SYMPTOM
Hiroki Hase 1 , Nobuhiko Joki 1 , Yuri Tanaka 1 , Hiroyasu Ishikawa 1 ,
Yasunori Takahashi 2 , Yoshihiko Imamura 2 , Sonoo Mizuiri 3 . 1 Division of
Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan;
2
Dialysis Center, Nissan Tamagawa Hospital, Tokyo, Japan; 3 Nephrology,
Toho University Omori Medical Center, Tokyo, Japan
Introduction and Aims: An initial event of acute coronary syndrome (ACS)
is an important predictor of future cardiovascular events and mortality from
all causes in patients with chronic kidney disease (CKD). We sought
to identify factors influencing occurrence of initial ACS events in new
maintenance hemodialysis patients without previous cardiac symptoms
during the predialysis phase of CKD.
Methods: One hundred twelve patients with no cardiac history underwent
coronary angiography or stress thallium-201 single photon emission com-
puted tomography to detect asymptomatic coronary artery disease (CAD)
within 1 month of beginning hemodialysis. In subsequent follow-up for a
median of 24 months, subjects experiencing an initial ACS were compared
with those who did not have such an event based on several clinical
parameters at the end of predialysis phase.
Results: Asymptomatic CAD was presented in 47 patients (42%), who had
a higher cumulative ACS rate than subjects without CAD (49% vs. 3%, p <
Sunday, July 16, 2006
0.001). Multivariate Cox regression analysis showed that the three following
parameters independently predicted ACS: presence of asymptomatic CAD
(hazard ratio or HR, 611.31; 95% confidence interval or CI, 14.07 to
26549.23; p < 0.001), diabetes (HR, 20.41; 95% CI, 2.07 to 200.00; p =
0.010), and each 1-mg/L increment in CRP (HR, 1.94; 95% CI, 1.27 to
2.94; p = 0.002).
Conclusions: Thus, in CKD patients starting hemodialysis who are free
of CAD symptoms the detection of CAD, the presence of diabetes, or
an elevated CRP at the end of the predialysis phase were significantly
associated with the occurrence of an initial ACS event.
SP499 DEFINITION OF THE DETERMINANTS OF URAEMIC
CARDIOMYOPATHY ASSESSED BY CARDIAC MAGNETIC
RESONANCE IMAGING
Patrick Mark 1 , Emmanouil Mazonakis 1 , Nicola Johnston 1 , Kevin Blyth 2 ,
Henry Dargie 2 , Alan Jardine 1 . 1 Renal Unit, Western Infirmary, Glasgow,
Scotland, United Kingdom; 2 Cardiology, Western Infirmary, Glasgow,
Scotland, United Kingdom
Introduction and Aims: Uraemic cardiomyopathy is an independent risk
factor for premature mortality in haemodialysis (HD) patients. Using
echocardiography three forms of uraemic cardiomyopathy have been re-
ported: left ventricular hypertrophy (LVH), dilated cardiomyopathy and
systolic dysfunction. Cardiac magnetic resonance imaging (CMR) is a
sensitive, volume independent technique to assess cardiac structure and
function and can identify previous myocardial infarction. Using CMR,
however, HD patients who do not have co-existent coronary disease, exhibit
only one form of cardiomyopathy - LVH (Kidney Int. in press, 2006). We
used CMR to assess the determinants of LVH, specifically the influence of
dialysis adequacy and duration of renal replacement therapy.
Methods: 114 HD patients (70.2% male; median age 52.5, range 24-70)
underwent CMR (Siemens Sonata 1.5T scanner) on a post dialysis day. Left
ventricular (LV) mass was measured from a stack of cine loops. Further im-
ages were acquired following iv gadolinium-DTPA. Demographic, clinical,
biochemical and haematological data were collected by case note review
and from the electronic patient record. LVH was defined as LV mass index
(LV Mass/Body Surface Area) >84.1g/m2 (male) or 74.6g/m2 (female),
based on published normal LV dimensions for CMR.
Results: 80 (70.2%) patients had LVH. LVH was more common in
men (77.5% vs. 52.9%; Chi squared p<0.01). 23.6% patients had CMR
evidence of previous myocardial infarction. CMR evidence of previous
infarction was associated with poorer systolic function (ejection fraction
58.5% vs. 68.3%, p=0.045) and LV dilation (end systolic volume 79.0
vs. 50.1ml, p=0.034). There were significant negative correlations between
LV mass index and haemoglobin, albumin and Kt/V (Spearman’s R -
0.29, p=0.003; -0.28, p=0.020; -0.32, p=0.001 respectively). There were
significant correlations between LV mass index and both mean pre- and
post-dialysis systolic and diastolic blood pressure (BP), with the strongest
correlation with post-dialysis systolic BP (pre-dialysis systolic BP R=0.54,
diastolic BP R=0.38; post-dialysis systolic BP R=0.60, diastolic BP R=0.48;
all p<0.001). Additionally there was a correlation between LV mass index
and serum parathyroid hormone (R=0.31, p=0.014) and a weak non-
significant correlation with duration of renal replacement therapy (R=0.18,
p=0.06). Using a multivariate linear regression model (only entering one BP
variable) the only independent predictor of LV mass index was post-dialysis
systolic BP (HR 0.82, 95% CI 0.532-1.118).
Conclusions: Although multiple factors exhibit significant relationships
with LV mass in HD patients, the principal determinant of LVH patients
is blood pressure, chiefly post dialysis systolic BP. In the absence of
coronary artery disease (represented by previous myocardial infarction), HD
patients have only one form of uraemic cardiomyopathy - LVH. This is not
determined by uraemia directly but by hypertension and its determinants -
renal failure and anaemia. This has major implications for the treatment of
LVH and its sequelae.
Dialysis – Cardiovascular risk 1 iv183
SP500 FACTORS ASSOCIATED WITH DIFFERENT ANKLE
BRACHIAL INDEX LEVELS IN ASYMPTOMATIC
NON-DIABETIC HEMODIALYSIS PATIENTS
Saso Gelev 1 , Sonja Dzikova 1 , Goce Spasovski 1 , Aleksandar Sikole 1 ,
Katica Zafirovska 1 , Slavco Tosev 2 . 1 Department of Nephrology;
2
Department of Cardiology, Faculty of Medicine, Skopje, F.Y.R.M
Introduction and Aims: The aim of this study was to evaluate the
presence of peripheral arterial disease (PAD) in asymptomatic non-diabetic
hemodialysis (HD) patients, the reliability of the ankle brachial systolic
pressure index (ABI) measurements in diagnosis of PAD, and to analyze
the potential risk factors associated with different ABI levels.
Methods: In a cross-sectional study we examined 44 non-diabetic asymp-
tomatic HD patients (28 men, 16 women, mean age 48.1±17.3 years, HD
duration 86,22±49,17 months) without previous history of cardiovascular
disease. All patients underwent ABI measurement, high resolution B-mode
ultrasonography of the common carotid (CCA) and femoral (FA) arteries,
and transcutaneous Doppler flow velocity measurement of the FA and CCA.
We evaluated the relationship between clinical/biochemical parameters (time
averaged for the 12 months prior to entering the study) and haemodynamic
characteristics.
Results: Low ABI ≤ 0,9 (positive findings in diagnosing PAD) was detected
in 11 (25%) patients, high ABI ≥ 1,3 (incompressible arteries at ankle level)
in 19 (43,2%) patients, and ABI between 0,9-1,3 (normal range) was found
in 14 (31,8%) patients. Patients with ABI ≤ 0,9 had significantly (p< 0.05):
older age, higher pulse pressure, lower diastolic blood pressure, increased
intima media thickness (IMT) in CCA and FA, increased internal diameter
(ID) in CCA and FA, higher presence of atherosclerotic plaques in CCA
(90.9%) and FA (100%), increased flow velocity in CCA and FA, higher
LDL cholesterol, higher serum triglycerides, higher C-reactive protein,
lower serum albumin. Patients with ABI ≥ 1,3 had significantly (p< 0.05):
longer HD duration and higher serum calcium (Ca) levels. Patients with
normal range ABI had significantly (p< 0.05): lower serum phosphorus
(PO4 ), lower serum CaxPO4 and lower doses of CaCO3 . Patients with
ABI ≥ 1,3 had significantly (p< 0.05): high presence of atherosclerotic
plaques (CCA=57.9%/FA=63,2%) and increased IMT and flow velocity in
CCA and FA in proportion to patients with normal range ABI. Patients
with normal range ABI had high presence of atherosclerotic plaques
(CCA=35.7%/FA=42.9%). Multivariate analysis selected age, duration of
HD, IMT, atherosclerotic plaques, doses of CaCO3 , serum PO4 , LDL
cholesterol, and serum albumin as variables predictive (p< 0.05) of low
ABI. Multivariate analysis for patients with high ABI showed that the
strongest independent (p< 0.05) predictors of ABI ≥ 1,3 are duration of HD,
atherosclerotic plaques, serum PO4 , doses of CaCO3 , and serum albumin.
Conclusions: Our results suggest significant presence of PAD in asymp-
tomatic non-diabetic HD patients. We demonstrated that patients with high
and normal ABI levels had high percentage of atherosclerotic lesions, and
that ABI measurement is unreliable for diagnosis of PAD. We need to
examine systemic atherosclerotic conditions in HD patients even if they
have no symptom. Doses of CaCO3 , HD duration, serum PO4 , serum
LDL cholesterol and serum albumin are main emerging risk factors for
appearance and frequency of PAD in HD patients.
SP501 METABOLIC SYNDROME IN PATIENTS WITH CHRONIC
KIDNEY DISEASE ON MAINTENANCE HEMODIALYSIS
L. Soubassi, V. Filipponi, St. Papakonstantinou, G. Kosmadakis,
G. Tsangalis, St. Zerefos, D. Valis, N. Zerefos. Dialysis Unit, “Hygeia”
Hospital, Athens, Greece
Introduction and Aims: The metabolic syndrome (MS) is associated with
increased risk for cardiovascular disease (CVD).
To define the frequency of MS among hemodialysis patients (pts) and
evaluate the efficiency of management according guidelines.
Methods: One hundred eighty-five (M: 114, F: 71) HD pts aged 66.612.7
have been on chronic HD for 50.443.2 mo.They were evaluated for the
following factors: hypertension (BP), waist circumference (WTC), TG,
HDL, fasting blood glucose (FBG), BMI, detailed medical history, LDL
levels, smoking, coronary artery disease (CAD), diabetes mellitus (DM),
hyperlipidemia and according to the ATP III criteria for the diagnoses of
MS.
iv184 Dialysis – Cardiovascular risk 1 Sunday, July 16, 2006

Results: Of all our pts: 19% were smokers,33% were hypertensive, 32% SP503 VALUE OF ASSESSMENT OF MYOCARDIAL FATTY ACID
had documented CAD, 25% had DM and 25% were hyperlipidemic. 41.6% METABOLISM IN THE PREDICTION OF CONGESTIVE
of pts were overweight or obese (BMI 30), mostly women 20.8% vs 10% HEART FAILURE IN HEMODIALYSIS PATIENTS
of men, 7.6% had LDL >130, mostly men 2.2% vs. 1.1 of women with
Masato Nishimura 1 , Masaki Murase 2 , Tetsuya Hashimoto 3 ,
LDL = 173.541.6 vs. 138.22.5 respectively, 6% were on lipid lowering
Hiroyuki Kobayashi 3 , Satoru Yamazaki 3 , Koji Okino 4 ,
therapy (LDL = 10456). 6.5% were not aware about their abnormal FBG
Kazumasa Tsukamoto 5 , Hakuo Takahashi 6 , Toshihiko Ono 3 .
levels, 33% had SBP 130/85 mmHg and were receiving antihypertensive 1
Cardiovascular Division, Toujinkai Hospital, Kyoto, Japan; 2 Department
treatment. Forty-six pts (25%) had MS (Gr A), 74% men, 26% women,
of Internal Medicine, Toujinkai Hospital, Kyoto, Japan; 3 Department of
while 139 pts (75%) (Gr B) did not present the above syndrome. The results
Urology, Toujinkai Hospital, Kyoto, Japan; 4 Department of Surgery,
are summarized in the table:
Toujinkai Hospital, Kyoto, Japan; 5 Department of Environment and
Occupational Health, Toho University, Tokyo, Japan; 6 Department of
GR: A/B BP WTC>102M, TG>150 HDL>40M, FBG≥110
130/85mmHg >88F >50F Clinical Sciences and Laboratory Medicine, Kansai Medical University,
Hirakata, Osaka, Japan
M 149.6± 1.6 113± 8.5 262±90 30.8± 3.7 169±53
F 149± 11.4 99.6± 9.9 271±137 43±4.2 165±62 Introduction and Aims: Single-photon emission computed tomography
M 135± 5.5 110.8± 7.7 261±102 31.8±4.5 161±46 (SPECT) using an iodinated fatty acid analogue, iodine-123-β-methyl
F 133±.6 5.2 98.9± 8.3 235±99 34.5±5 156±54
iodophenyl-pentadecanoic acid (BMIPP), can assess myocardial metabolism
of a free fatty acid, which is a major energy substrate in the heart. We aimed
Statistically significant differences between Gr A and B were found for: BP, to evaluate the usefulness of BMIPP SPECT to predict the occurrence of
WTC in men, TG, HDL, FBG. congestive heart failure in maintenance hemodialysis patients.
Conclusions: The improvement of these metabolic indices may contribute Methods: BMIPP SPECT was prospectively performed in 90 asymptomatic
to the decrease of cardiovascular complications in this population. hemodialysis patients (male/female, 56/34; mean age, 61.9 years), who were
followed up at least for 1 year. All patients had undergone echocardiography
in the same week of SPECT and coronary angiography within 60 days
SP502 TRADITIONAL AND NONTRADITIONAL RISK FACTORS after SPECT. Blood was collected before dialysis at the same week of
FOR ATHEROSCLEROSIS IN HEMODIALYSIS PATIENTS SPECT, and plasma B-type natriuretic peptide (BNP) concentrations were
determined. SPECT findings were graded in 17 segments on a five-point
Sebastjan Bevc 1 , Radovan Hojs 1 , Robert Ekart 1 , Tanja Hojs Fabjan 2 ,
scale (0, normal uptake; 4, none) and assessed as a summed score.
Breda Pecovnik Balon 1 . 1 Clin. Dept. of Internal Medicine, Dept. of
Results: During a follow-up lasting 27.0 ± 11.6 months, 11 patients caused
Nephrology, Teaching Hospital Maribor, Maribor, Slovenia; 2 Dept. of
congestive heart failure needing hospitalization. Patients with congestive
Neurology, Teaching Hospital Maribor, Maribor, Slovenia
heart failure had a higher rate of minor coronary lesions which had needed
Introduction and Aims: The risk for coronary artery disease (CAD) is no intervention (54.4% versus 16.5%, P = 0.004), lower mean left ventricular
higher among patients with end-stage renal disease than in the general ejection fraction (47.0 ± 12.3% versus 63.0 ± 14.1%, P = 0.001), higher
population. However, this excess risk for CAD is not entirely explained mean age (71.0 ± 13.4 years versus 60.6 ± 10.0 years, P = 0.003), higher
by traditional risk factors for cardiovascular disease. The aim of our study mean plasma BNP concentration (599.7 ± 621.8 pg/ml versus 318.9 ±
was to determine the relationship between some traditional (age, arterial 278.2 pg/ml, P = 0.011) and greater BMIPP summed score (24.1 ± 17.6
hypertension, smoking, total cholesterol, high-density lipoprotein (HDL) versus 7.9 ± 7.8, P = 0.0001) than those without heart failure. Stepwise
cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides) and Cox hazard analysis showed that the occurrence of congestive heart failure
non-traditional risk factors (lipoprotein(a), apolipoprotein A, apolipopro- was significantly associated with left ventricular ejection fraction (Hazard
tein B, homocysteine, calcium, phosphorus, parathyroid hormone) and ratio, 0.953; 95% confidence interval, 0.914-0.993; P = 0.022) and BMIPP
asymptomatic atherosclerosis in hemodialysis (HD) patients. summed score (Hazard ratio, 1.059; 95% confidence interval, 1.019-1.100;
Methods: In our study 91 HD patients were enrolled, 39 (43%) were P = 0.003). Kaplan-Meier estimates revealed that a congestive heart failure-
women and 52 (57%) men (mean age was 53 years, ranged from 19 to 79 free rate at 3.9 years was 69% in patients with a BMIPP summed score of
years). Using B-mode ultrasonography, intima-media thickness (IMT) was 10 or more and 95% in patients with a BMIPP summed score less than 10.
measured and plaque occurrence in the carotid arteries were determined.
Systolic and diastolic blood pressure were routinely measured before and
after each dialysis (mean value of 1 month measurements was used).
Information on smoking habits was obtained by questionnaire, patients were
divided into smokers (present or former) and nonsmokers. Biochemical
parameters were measured by routine laboratory methods, parathyroid
hormone (iPTH) was measured by radioimmunoassay.
Results: The mean IMT value was 0.75, ranged between 0.4 to 1.3 mm and
59 (65%) HD patients had plaques. ITM values correlated with age (r=0.589;
p<0.0001), total cholesterol (r=0.305; p<0.003), LDL cholesterol (r=0.317;
p<0.002) and apolipoprotein B (r=0.230; p<0.028). Plaque occurrence cor-
related with age (r=0.493; p<0.0001), total cholesterol (r=0.359; p<0.0001),
HDL cholesterol (r=-0.248; p<0.018), LDL cholesterol (r=0.354, p<0.001),
triglycerides (r=0.402; p<0.0001) and apolipoprotein B (r=0.280, p<0.007).
With multiple regression analysis of traditional and non-traditional risk
factors only relationship between IMT and age was found (p=0.0001).
When only non-traditional risk factors were analyzed with multiple regres-
sion analysis relationship between ITM and apolipoprotein B was found
(p=0.04).
Conclusions: Our results indicate that atherosclerosis in HD patients was Conclusions: Impaired myocardial fatty acid metabolism may predict the
associated with traditional and also some non-traditional risk factors such is occurrence of congestive heart failure in hemodialysis patients, indepen-
apolipoprotein B. dently of left ventricular systolic dysfunction.
Sunday, July 16, 2006 Dialysis – Cardiovascular risk 1 iv185

SP504 BLOOD PRESSURE VARIABILITY IN HAEMODIALYSIS We have investigated the PON1 gene polymorphism (192Gln/Arg and
PATIENTS IN ENGLAND AND WALES 55 Leu/Met) in certain diseases with significant oxidative stress and in a
control group. We have also studied some of the factors influencing endothel
J.M. Harper 1 , A.V.R. Rao 2 , A.J. Williams 3 , D.A. Ansell 2 . 1 Link 6C Renal
dysfunction, such as the levels of endothelin and its substrate, big-endothelin
Unit, Royal Linverpool University Hospital, Liverpool, United Kingdom;
2 and also, homocystein levels.
UK Renal Registry, Southmead Hospital, Bristol, United Kingdom; 3 Renal
Methods: Patients above 65 years were included in the study: pre-dialysed
Unit, Morriston Hospital, Swansea, United Kingdom
kidney patients (GFR=30-60; n=73) and dialysed ESKD patients (GFR<15;
Introduction and Aims: In the UK, patients with clinical problems dialyse n=82). We have taken the patients who suffer from diabetes mellitus (DM)
in the main units for more supervised medical care. One would therefore separately in both groups. The third group consisted of control patients
predict greater blood pressure (BP) variability for patients dialysing in main without kidney disease and DM (n=36).
units. The PON1 gene polymorphism was measured with real time PCR (Light
Methods: Only main units with associated satellites were studied. Patients Cycler) technique using melting-point analysis, and we also calculated
were assigned to a main unit or satellite by their location 90 days after PON1 gene polymorphism based on the results of paraoxonase activity
starting haemodialysis (HD). Pre and post-HD BP measurements were measurements. ELISA method was adapted for measuring big-endothelin,
obtained for each quarter and analysed using the Mixed Model Analysis of endothelin and homocystein levels.
Variance. Values were adjusted for age and the year each patient started HD. Results: The distribution of PON1 gene polymorphisms was similar in
Residual variance was also calculated. This covers factors that may cause all groups. We have found a significantly lower the paraoxonase activity
variability but were not included in the model e.g. ethnicity. in dialysed patients compared to the control group (p<0.05). The big-
Results: The first BP recorded after 90 days was analysed for 1300 patients endothelin and endothelin levels also showed a significant difference in the
from 30 main units and 465 patients from 67 satellites who started HD patient groups and the control group. We have found normal levels in the
between 2003 and 2004. Satellite units varied more for pre-HD SBP, PP control group, whereas big-endothelin and homocystein levels were higher
and post-HD PP by 11-25%. Main units varied by 9-54% for the other BP in the other groups, the highest level being measured in dialysed patients
parameters. None reached significance. (p<0.0001). Regarding endothelin, significantly higher levels (p<0.05)
BP data for 8 consecutive quarters were analysed for 1615 patients from were measured in pre-dialysed kidney patients compared to the control
19 main units and 544 patients in 29 satellites who started HD between group.
1998 and 2004. Comparing units, satellites varied by 15-41% for all pre-HD There was no significant difference in the investigated parameters in the
BP parameters but none reached significance. Main units varied by 80- DM patients compared to other, non-DM patients in the same subgroup in
223% for post-HD BP parameters. Only post-HD SBP reached significance. either the dialysed or the pre-dialysed patient groups.
Variability for patients within a given centre was negligible, 3-5% for Conclusions: The level of serum paraoxonase with antioxidant effect
satellites and 1-4% for main units. was lower in all kidney patients than in the control group. However, the
In Bristol, 317 HD patients were studied between June and July 2005. BP distribution of the Q192R gene polymorphism was approximately the same
varied significantly with age but not by location. BP was significantly higher in all groups.
after the 3-day interval. The levels of the above measured factors, which affect lipid methabolism
Conclusions: Greater variability in pre-HD BP was evident between the and endothel dysfunction, were different in the control group and the patient
satellites, an unexpected finding. Variations in case mix and level of medical groups. Protective factors show lower levels in patient groups, while factors
supervision are possible explanations. The significant variability in post-HD enhancing atherogenesis showed higher levels, thus, dialysis and kidney
SBP between main units may reflect cardiac instability in patients with high disease are important risk factors for atherosclerosis. These differences were
comorbidity or intercurrent problems. the most significant in the dialyzed group compared to the control group,
which shows that the severity of kidney insufficiency is related to the risk
BP variability in Bristol Haemodialysis patients factors of atherosclerosis.
Parameter Pre-HD Post-HD
SBP DBP PP SBP DBP PP
No. of observations 8071 8068 8068 7967 7967 7967 SP506 CORRELATION BETWEEN PARATHYROID HORMONE
Main vs Satellite unit (p) 0.233 0.056 0.593 0.446 0.095 0.522 AND CARDIAC ABNORMALITIES IN CHRONIC KIDNEY
Mon-Tue (mean, mmHg) 141.3 73.2 68.1 132.6 69.5 63.1 DISEASE PATIENTS ON MAINTENANCE HEMODIALYSIS
Wed-Thu (mean, mmHg) 138.2 72.2 66.0 131.3 68.7 62.6
Fri-Sat (mean, mmHg) 137.8 72.1 65.7 130.8 68.6 62.2 Hideki Fujii 1 , Jong Il Kim 2 , Takaya Abe 1 , Michio Umezu 1 ,
MonTue vs WedThu (p) <0.001 0.0006 <0.001 0.002 0.007 0.194 Masafumi Fukagawa 1 . 1 Division of Nephrology and Dialysis Center, Kobe
MonTue vs FriSat (p) <0.001 <0.001 <0.001 <0.001 0.0009 0.023 University Graduate School of Medicine, Kobe, Hyogo, Japan;
WedThu vs FriSat (p) 0.336 0.705 0.924 0.464 0.806 0.643 2
Department of Internal Medicine, Chibune Hospital, Osaka, Japan
This is the first time BP has been shown to vary significantly at different Introduction and Aims: The number of chronic kidney disease (CKD)
times during the HD week. It is not currently known which BP parameter patients with hemodialysis is increasing annually and most of them have
will correlate most closely with cardiovascular mortality. Registries need to cardiac abnormalities. Many investigators have demonstrated that plasma
collect BP data in a standardised way to enable such analyses. parathyroid hormone (PTH) level is correlated with left ventricular hypertro-
phy (LVH). In addition, there are a few reports demonstrated a relationship
between PTH and left ventricular (LV) dysfunction. However, their patho-
SP505 THE ANALYSIS OF PON1 GENE POLYMORPHISM AND physiological mechanisms are complex and the details remain unclear. The
FACTORS INFLUENCING ENDOTHEL DYSFUNCTION IN purpose of this study was to evaluate the relationship between PTH or other
ELDERLY KIDNEY PATIENTS factors and cardiac abnormalities such as LVH or LV dysfunction.
Methods: A total of 55 patients (26 men and 29 women), who had
Marianna Zsom, Emoke Endreffy, Eszter Karg, Attila Orosz, Sandor Turi.
dialysis therapy for more than 12 months, were included in this study.
Gambro Dialysis Center, Gambro Dialysis Center, Szeged, Hungary;
Patients with coronary artery diseases, idiopathic cardiomyopathy, valvular
Pediatric Clinic, University of Szeged, Szeged, Hungary; Pediatric Clinic,
diseases or arrhythmia were excluded. Plasma PTH, brain natriuretic peptide
University of Szeged, Szeged, Hungary; Gambro Dialysis Center, Gambro
(BNP) measurements, other blood examinations and echocardiography were
Dialysis Center, Budapest, Hungary; Pediatric Clinic, University of Szeged,
performed in all patients. They were divided into two groups based on plasma
Szeged, Hungary
PTH level. (PTH level of 299 pg/ml or less; group A, n=40, 300 pg/ml or
Introduction and Aims: One of the main functions of HDL is the inhibition more; group B; n=15). In addition, we chose the patients with plasma PTH
of LDL oxidation, which is effected by an attached antioxidant enzyme, level of more than 500 pg/ml from group B and classified them in group C
namely paraoxonase. The enzyme is coded by chromosome number 7 (n=8).
(7q21-22) and it has three known isoforms (QQ, QR, RR) with different Results: In echocardiographic parameters, there were no significant differ-
activity levels. ences between group A and B. LVMI and IVST were significantly greater
iv186 Dialysis – Cardiovascular risk 1
in group C than in group A (LVMI: 189.5±62.1 v.s 149.2±41.2 g/m2 ;
p<0.05, IVST: 13.0±2.3 v.s 11.3±2.0 mm; p<0.05). Plasma PTH level was
not significantly correlated with any echocardiographic parameters such as
left ventricular mass index (LVMI), relative wall thickness (RWT), fraction
shortening (FS), left ventricular diastolic dimension (LVDd) and E/A in
all patients. By contrast, BNP was significantly correlated with LVDd
(p<0.001), LVDs (p<0.001), FS (p=0.010), and LVMI (<0.001).
To clarify the factors correlated with LVH, LV systolic dysfunction, and
LV diastolic dysfunction, we evaluated the relationship between LVMI, FS
or E/A and other factors in all patients. LVMI was significantly associated
with hypertension (p<0.05), hematocrit (p<0.05), and serum albumin level
(p<0.05). FS was significantly associated with hematocrit (p<0.05). E/A
was significantly associated with age (p<0.005), hypertension (p<0.05) and
serum albumin level (p<0.01).
Conclusions: Plasma PTH was not significantly associated with cardiac
abnormalities such as LVH or decreased LV function in overall study
patients. However, it could influence LVH in patients with remarkably
high plasma PTH level. It seems that PTH may not play a major role in
the genesis of cardiac abnormalities in CKD patients with dialysis and
numerous other factors may contribute to the pathogenesis in these patients.
SP507 GENE POLYMORPHISMS AND SERUM LEVELS OF
FETUIN-A (AHSG) IN HEMODIALYSIS PATIENTS
Mario Cozzolino 1 , Maria Luisa Biondi 2 , Maurizio Gallieni 1 ,
Claudia Brambilla 1 , Olivia Turri 2 , Sergio Papagni 3 , Nicola Mongelli 3 ,
Luigi Civita 3 , Diego Brancaccio 1 . 1 Renal Division, S. Paolo Hospital,
University of Milan, Milan, Italy; 2 Division of Clinical Chemistry and
Microbiology, S. Paolo Hospital, Milan, Italy; 3 Dialysis Unit, CBH,
Bisceglie (BA), Italy
Introduction and Aims: Vascular calcification (VC) and accelerated
atherosclerosis are major causes of cardiovascular morbidity and mor-
tality in hemodialysis (HD) patients. “Protective” proteins associated with
reduced vascular calcification may play a key role in preventing VC in
renal failure. Fetuin-A is a circulating inhibitor of VC that has been asso-
ciated with inflammation and cardiovascular mortality in HD patients. In
the present study we investigated the associations between serum fetuin-A
levels and its gene (AHSG) polymorphisms in a HD population.
Methods: 96 patients on stable chronic HD treatment and 57 healthy
controls were genotyped for the common polymorphisms on the AHSG
(T256S). In addition, serum fetuin-A levels were tested by using an ELISA
Kit (Epitope Diagnostics, Inc, San Diego, USA).
Results: In this study serum fetuin-A levels are lower in HD patients
(0.35±0.11 g/L) compared to healthy controls (0.62±0.31 g/L, p<0.05). In
both HD and control group, the distribution of the AHSG gene did not show
significant association between low serum fetuin-A levels and the Ser/Ser
genotype, known to be associated with a higher cardiovascular mortality
risk in HD population (Stevinkel P et al, Kidney Int 2005; 67: 2383-2392).
Moreover, the distribution of AHSG gene polymorphisms in HD patients
and in healthy controls is similar (Table 1).
AHSG T256S Polymorphisms in Hemodialysis Patients
Healthy Controls (n=57) Hemodialysis Patients (n=96)
Thr/Thr 54% 61%
Thr/Ser 40% 34%
Ser/Ser 6% 5%
Conclusions: This study suggests that patients with chronic renal failure
in HD treatment have a similar polymorphism distribution of AHSG gene
compared to normal population and that the reduction of serum fetuin-A
levels in HD patients is not associated to alteration on the distribution of
AHSG T256S polymorphisms.
Sunday, July 16, 2006
SP508 EFFICIENCY OF HOMOCYSTEINE-LOWERING THERAPY
IN PATIENTS WITH CHRONIC RENAL INSUFICIENCY
Vaclav Monhart 1 , Vera Hamplova 1 , Vaclav Blaha 2 , Bohuslav Choluj 3 .
1
Nephrology Unit, Department of Internal Medicine, 1st Faculty of
Medicine, Charles University and Central Military Hospital, Prague, Czech
Republic; 2 Faculty of Military Medicine, University of Defence, Hradec
Kralove, Czech Republic; 3 KlinLab, Prague, Czech Republic
Introduction and Aims: Hyperhomocysteinemia is acknowledged as in-
dependent cardiovascular risk factor. Cardiovascular complications are the
most frequent causes of high morbidity and mortality in patients with
chronic renal insuficiency (CHRI). The aim of our study was to analyse the
effect of nutritional therapy to lower total plasma homocysteine level (tHcy)
in patients with CHRI.
Methods: There were studied 326 pts with CHRI and hyperhomocysteine-
mia (224 males and 102 females, mean age of 71±11 yrs). The most
frequent causes of CHRI were chronic intersticial nefritis, hypertensive
nephroangiosclerosis and diabetic nephropathy. Group of 55 (17%) pts (45
males and 10 females; mean age of 72±11yrs) was followed-up for a period
of 12 months. All pts except three had arterial hypertension. Mean serum
creatinine level was 187.5±81.9 μmol/l. There was present mild or moderate
hyperhomocysteinemia - tHcy 25.1±9.2 (15.1- 68.8) μmol/l. All pts were
suplemented with Kardioprotektin® (containing 1 mg of folic acid, 5 mg of
vitamin B6 and 20 μg of vitamin B12) at dose of one tablet/day. At the
beginning and at the end of this therapy there were evaluated the following
laboratory data: tHcy, hemoglobin, LDL cholesterol, serum creatinine and
glomerular fitration rate.
Results: Within a period of 8.0±3.4 months tHcy decreased from 25.1±9.2
μmol/l to 16.1±6.1 μmol/l (-36%). Complete normalisation of tHcy (<15
μmol/l) was present in 33 (60%) pts (subgroup A), in 18 (56%) of them
during 6 months. A partial reduction of tHcy was achieved only in 14 (25%)
pts and in 8 (15%) pts tHcy remained unchanged (subgroup B). Pts of
subgroup A in comparison with subgroup B showed significantly lower both
initial (163.0±44.4 vs 226.7±110.2 μmol/l) and final values (155.2±51.3
vs 230.7±131.4 μmol/l) of serum creatinine (p<0.01) as well as initial
(21.6±4.6 vs 30.7±11.8 μmol/) and final values (12.3±2.4 vs 22.2±5.2
μmol/) of tHcy (p<0.01). On the other hand pts of subgroup A showed
higher initial (145.2±14.6 vs 131.4±18.0 g/l) and final values (141.5±17.2
vs 128.0±19.8 g/l) of hemoglobin in comparison with pts of subgroup B
(p<0.01). There was found out no significant difference in LDL cholesterol
between both subgroups.
Conclusions: 1) Nutritional therapy with Kardioprotektin® led to complete
normalisation or reduction of tHcy in 47 (85%) pts. 2) The achievement of
a complete normalisation of tHcy depended on severity of CHRI and degree
of hyperhomocysteinemia.
SP509 SERUM LEVELS OF ADHESION MOLECULES, ICAM-1,
V-CAM AND E-SELECTIN ARE NOT INDEPENDENT
PREDICTORS OF 5 –YEAR MORTALITY IN PATIENTS
WITH CHRONIC RENAL FAILURE
Ramos Natàlia 1 , Segarra Alfons 1 , Chacón Pilar 1 , Caparros Sonia 1 , De la
Torre Judith 1 , Argelaguer Xavier 2 , E. Alvarez 2 , Camps Joaquim 1 .
1
Nephrology and Biochemistry, H. Vall de Hebrón, Barcelona, Spain;
2
CDR Monolab, Barcelona, Spain
Introduction and Aims: Background: Recent evidences indicate that solu-
ble endothelial cell adhesion molecules are increased and may participate
in atherogenesis in patients with chronic renal failure. However, the in-
dependent relationship between the serum levels of these molecules and
cardiovascular morbidity or mortality remains to be proven.
Aim: To investigate the biochemical associations and the relative role of
circulating ICAM-1, VCAM-1 and E-selectin as independent predictors of
cardiovascular events in patients with progressive chronic renal failure.
Methods: A cohort of 285 patients with GFR < 60 ml/min were included
in the study and prospectively followed for 5 years. Baseline demographic
and clinical characteristics were obtained from medical records. End points
were dead or non-fatal cardiovascular events. Serum levels of sVCAM-1,
sICAM-1 and sE-selectin were determined 3 times during the first year of
follow-up and then every year along with classic cardiovascular risk factors,
and the inflammation markers CRP and IL-6.
Sunday, July 16, 2006 Dialysis – Cardiovascular risk 1 iv187

Results: At the end of follow-up, 90/285 (31.5%) patients had suffered time on dialysis therapy and classic endothelial risk factors. These data
a cardiovascular event and 70/285 (24.5%) patients had died, 39 (55.7%) suggest that endothelial injury could be a link between the inflammatory
from cardiovascular disease. Significant correlations were observed between response and CAD and raises the possibility that there could be additional
both IL-6/CRP and sVCAM-1 (R: 0.43 R: 0.5; P<0.01) and sICAM-1 mechanisms leading to endothelial injury in hemodialysis patients.
(R: 0.51 R: 0.41; P<0.001) and sE-selectin (R: 0.3 R: 0.21; P<0.01).
Both CRP, and levels of soluble adhesion molecules were significantly
higher in males (P: 0.03), smokers (p:0.043) and patients with baseline SP511 TRADITIONAL VERSUS NON-TRADITIONAL RISK
cardiovascular disease (p: 0.001). In univariate analysis, cardiovascular FACTORS FOR VASCULAR INJURY IN HAEMODIALYZED
morbidity/mortality was associated with age, high blood pressure, left PATIENTS: DOPPLER ECHOGRAPHY APPROACH
ventricular hypertrophy, GFR, urinary protein excretion, renal vascular
Gabriel Mircescu 1 , Ligia Petrescu 1 , Simona Hildegard Stancu 1 , Mircea
disease, male gender, smoking, time, high PTH levels, low HDL- C,
Niculae Penescu 1 , Christian Klein 2 , Liliana Garneata 1 . 1 Nephrology,
high ferritin, low albumin, CRP and serum levels of sVCAM-1, sICAM-1
“Carol Davila” Clinical Hospital of Nephrology, Bucharest, Romania;
and sE-selectin (p< 0.01 in all cases). Multivariate Cox –proportional 2
Dialysis, “Carol Davila” NephroCare Dialysis Centre, Bucharest,
regression analysis showed previous coronary artery disease, peripheral
Romania
vascular disease, left ventricular hypertrophy, CRP and age as independent
predictors of both cardiovascular mortality or morbidity. Once excluded the Introduction and Aims: Doppler echography evaluation of carotid artery
presence of previous cardiovascular events from the model, multivariate Cox is a non-invasive procedure to assess the vascular status of haemodialyzed
–proportional regression analysis included male gender, age, blood pressure, (HD) patients.
smoking, low HDL c, and CRP as independent predictors of cardiovascular Methods: Clinical, laboratory and ecographic data from 146 HD patients
mortality but not serum levels of sVCAM-1, sICAM-1 or sE-selectin. from a large single centre (65% males) were obtained in order to determine
Conclusions: In patients with chronic renal failure, elevated serum concen- the vascular status.
trations of soluble adhesion molecules were associated with inflammation Results: Carotid plaques were identified in 66.4% of patients (93.8%
markers and with the presence of cardiovascular disease but were not calcified; 38.1% inhomogeneous, 6% homogeneous plaques). Significant
independent predictors of mortality at 5 years. greater percentages of patients with carotid plaques were males, smokers and
had vascular nephropathies as underlying disease. These patients were older
at HD initiation, had greater BMI, higher values of serum cholesterol, serum
SP510 RELATIONSHIP BETWEEN INCREASED CIRCULATING calcium, serum PTH, CRP and higher pulse pressure. Aortic atheromatosis
LEVELS OF ENDOTHELIAL-CELL GLYCOPROTEINS and valvular calcifications were more prevalent in patients with carotid
AND CARDIOVASCULAR RISK IN NON-DIABETIC plaques.
PATIENTS TREATED WITH HAEMODIALYSIS
Ramos Natàlia 1 , Segarra Alfons 1 , Chacón Pilar 1 , X. Argeler 2 , Plaque score 0 Plaque score>0
E. Alvarez 2 , Caparros Sònia 1 , De la Torre Judith 1 , Camps Joaquim 1 . Patients (%) 34 66
1
Nephrology and Biochemistry, H Vall de Hebrón, Barcelona, Spain; 2 CDR Vascular nephropathies (%) 8.4 20.8*
HD vintage (years) 7.42±6.43 8.528±6.9
Monolab, Barcelona, Spain Gender (males, %) 38.8 58.6*
Background: Studies in the general population have shown a positive Age (years) 48.89±11.79 56.8±11.3*
Age at HD initiation (years) 41.44±13.51 48.28±13.98*
association between cardiovascular disease and increased plasma levels Smokers (%) 20.1 34.2
of type 1 plasminogen activator inhibitor (PAI-1) and fibrinogen. It has BMI (kg/m2 ) 22.58±3.57 24.28±3.9*
been demonstrated that dialysis patients have elevated glycoprotein-related CRP (mg/L) 4.9±3 8.2±5.9*
molecules, PAI-1 Ag and PAI activity, but little is known about the factors Serum cholesterol (mg/dL) 167.36±40.3 188.4±35*
leading to these alterations and the relationship between CAD and increased Serum calcium (mg/dL) 8.8±0.8 9.23±0.8*
Serum phosphate 5.63±1.65 5.93±1.65
PAI-1 remains speculative.
PTH[pg/mL, mean(range)] 483.16(1-2550) 268(8-1500)*
Objective: 1) to analyze the clinical and biochemical variables associated Pulse pressure (mmHg) 54.61±16 57.55±17*
with elevated circulating levels of endothelial cell molecules in patients Aortic atheromatosis (%) 44.1 76.8
on hemodialysis and 2) to determine the role of inflammatory cytokines, Valvular calcification (%) 31.3 62.1
endothelial cell glycoproteins and fibrinolysis inhibitors as independent risk * - statistically significant
factors for ischemic heart disease in dialysis patients.
Participants: Two-hundred randomly selected, nondiabetic dialysis patients Sixty percent of patients had multiple plaques (plaque score >2).Compared
and 30 healthy matched volunteers. to the patients with plaque score <2, they were significantly more males
Measurements: Predialysis plasma levels of thrombomodulin, TPA Ag, (61 vs 41%) and had vascular nephropathy as the leading cause of ESRD
TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, TAT complexes, (30 vs 8%). Patients with higher plaque score were older (59.7±11.4 vs
FPA, CRP, IL-1b and aTNF. Serum levels of lipids, apoproteins A1 and B, 52.52±9.8), had higher BMI (24.8±3.9 vs 23.3±3.9), higher left ventricular
and albumin. mass (57.9±14.2 vs 47.9±11.3). They had higher prevalence of angina (44
Results: Forty-six patients (23%) had evidence of CAD. The clinical vs 22%), aortic atheromatosis (88 vs 60%), valvular calcifications (74 vs
and biochemical variables associated with CAD in the univariate analysis 43%); the plaques were inhomogeneous (49 vs 21%) or calcified (100 vs
included age, time on dialysis, male sex, number of packets/year, high blood 85%).
pressure, fibrinogen, apolipoprotein B, PAI-1 Ag, PAI-1 activity, CRP, TAT In the analyzed patients, IMT was 1.1±0.2mm, with only 9.5% patients with
and FPA. In the multiple regression analysis, CRP, smoking, blood-pressure, IMT <0.8mm. Patients with IMT>1.25 had similar characteristics to those
fibrinogen and HDL cholesterol accounted for 30% of PAI-1 variability with higher plaque score. As in case of plaque score >2 and unhomogenous
whereas time on dialysis, blood pressure, fibrinogen and PAI-1 accounted plaque, in those with IMT>1.25mm higher CRP values were noted.
for 35% variability in TAT levels. Logistic regression analysis found age, Conclusions: In the studied cohort, characterized by a longer HD vintage
HDL cholesterol, sex, high blood pressure, CRP, PAI–1 activity and FPA to and a low mortality rate (5%/year), vascular changes were frequently found.
be independent predictors of CAD. This model correctly classified 85% of The presence of vascular injury, as well as its extent seem to be associated
patients as having or not having CAD and showed adequate calibration for with traditional risk factors for atherosclerosis (age, gender, underlying
all risk categories. When tested in an independent sample of patients, the kidney disease, smoking, serum cholesterol, body weight, inflammation).
predictive model correctly classified 82.35% of the patients. The high percentage of calcified and possibly stable plaques could be the
Conclusions: Hemodialysis patients suffer a state of endothelial cell consequence of the mineral metabolism disturbances (with a tendency to
activation and increased intravascular fibrin formation, both of which hypercalcemia and hyperparathyroidism).
are independent predictors of CAD. The increased circulating levels of
endothelial-related glycoproteins was clearly associated with a chronic
inflammatory state and could be only partly explained by the length of
iv188 Dialysis – Cardiovascular risk 1
SP512 eNOS GENE POLYMORPHISMS CONTRIBUTE TO THE
SEVERITY OF CAROTID ATHEROSCLEROSIS IN DIALYSIS
PATIENTS
Belinda Spoto, Alessandra Testa, Rosa Maria Parlongo, Anna Pisano,
Francesca Mallamaci, Giovanni Tripepi, Carmine Zoccali. CNR-IBIM, Inst.
Of Int. Med, Clin.Epid.& Physiopath. of Renal Dis. and Hypert., Reggio
Calabria, Italy
Introduction and Aims: Reduced synthesis of nitric oxide (NO) is an
emerging atherogenic risk factor in dialysis patients. This phenomenon
can be due to metabolic derangements peculiar to end-stage renal disease
(ESRD), such as accumulation of asymmetric dimethyl arginine (ADMA),
and to genetic factors, i.e. endothelial nitric oxide synthase gene (eNOS)
polymorphisms. The T allele of eNOS G894T polymorphism is a predictor
of cardiovascular mortality (J Hypertens 2005;23: 1825-1830) and severity
of carotid atherosclerosis (Am J Hypertens 2005; 18: 1549-1555) in ESRD.
However, it is still controversial if this polymorphism is functionally active
or if it is in linkage disequilibrium with other polymorphisms in the same
gene, such as T-786C.
Methods: We examined this problem by analyzing the relationship between
carotid intima-media thickness (IMT) (assessed by Eco Color Doppler) and
the number of risk alleles, T allele (G894T polymorphism) and C allele
(T-786C polymorphism), of the two above mentioned polymorphisms in a
series of 147 ESRD patients.
Results: IMT was significantly thicker (P=0.01) in patients with TT geno-
type (G894T polymorphism) (1.14± 0.35 mm) than in patients with TG
(1.07± 0.22 mm) or GG (0.98± 0.21 mm) genotypes and a similar associa-
tion was observed for the T-786C polymorphism (CC: 1.23± 0.27 mm; CT:
1.07± 0.25 mm, TT: 1.00± 0.22 mm, P=0.02). The relationship between
IMT and the risk alleles of the two polymorphisms remained statistically
significant (β=0.24, P=0.02 and β=0.20, P=0.01, respectively) also after ad-
justment for traditional (age, gender, smoking, diabetes, cholesterol, blood
pressure), non traditional (haemoglobin, albumin, calcium-phosphate) and
emerging risk factors (C-reactive protein and ADMA) for atherosclerosis.
Furthermore, there was a direct association between the “dose” of risk alle-
les and IMT (no risk allele: 0.97+0.22 mm, 1 risk allele: 1.03+0.20 mm, 2
risk alleles: 1.07+0.22 mm, ≥3 risk alleles: 1.23+0.36 mm, P<0.001). This
association remained statistically significant also in a multiple regression
model including ADMA and other relevant risk factors.
Conclusions: In dialysis patients the risk alleles of the two eNOS poly-
morphisms G894T and T-786C are associated to the severity of carotid
atherosclerosis. This phenomenon suggests that the effect of the G894T
polymorphism on carotid atherosclerosis is independent or not accounted
for the hypothetical linkage disequilibrium with the T-786C polymorphism.
The genetic interaction between the two polymorphisms involved in NO
synthesis contributes to the severity of atherosclerosis independently from
endogenous factors that influence the same gene product (i.e. ADMA) in
ESRD.
SP513 MINERAL METABOLISM, MORTALITY AND MORBIDITY IN
DIALYSIS: RISCAVID STUDY
Vincenzo Panichi 1 , Riccardo Giusti 2 , Giovanni Manca Rizza 3 ,
Sabrina Paoletti 1 , Valentina Marchetti 1 , Cristina Consani 1 ,
Emanuela Mantuano 1 , Raffaele Caprioli 4 , Giovanni Grazi 3 ,
Mauro Aloisi 5 , Alessandro Antonelli 2 , Giacli’ Donati 3 , Roberto Bigazzi 6 ,
Paolo Rindi 4 , Giuliano Barsotti 1 , Roberto Palla 7 . 1 Internal Medicine,
University of Pisa, Pisa, Italy; 2 Nephrology and Dialysis, Lucca, Italy;
3 the mean left CCA-IMT was 0.67±0.16 mm. Based on ultrasonographic
Nephrology and Dialysis, Pontedera, Italy; 4 Nephrology and Dialysis,
Pisa, Italy; 5 Nephrology and Dialysis, Versilia, Italy; 6 Nephrology and
Dialysis, Livorno, Italy; 7 Nephrology and Dialysis, Massa, Italy
Introduction and Aims: Elevated cardiovascular (CV) mortality and mor-
bidity in ESRD is due to the coexistence of non traditional risk factors due
to the uremic state. RISCAVID (Cardiovascular risk in dialysis) study is an
observational and prospective study of the over 800 patients in hemodialysis
and peritoneal dialysis of the north-west part of Tuscany. Aim of the study,
started on June 2004, is to elucidate the role of various risk factors on
mortality and morbidity in dialysed patients; in particular we here focus our
attention on mineral metabolism disorders.
Methods: At the time of the enrolment demographic, clinical and laboratory
Sunday, July 16, 2006
data of the whole population and comorbidity conditions (CV disease),
established by anamnestic and instrumental information, were registered.
Mineral metabolism was studied by the determination of serum phosphorus
(P), calcium (Ca) (Autoanalyzer), calcium x phosphorus product (CaxP)
and intact parathyroid hormone (iPTH) (IRMA). We also recorded Ca
supplementation, use of vitamin D, phosphate binders and cinacalcet.
Population was followed up for 12 months reporting both fatal and nonfatal
CV(myocardial infarction, stroke, ictus) events.
Results: Our data confirm the high mortality rate in dialysed patients
(all-cause mortality 14%/year; CV mortality 6.5%/year). The baseline
analysis of the population showed a mean Ca level of 9.18±3.2mg/dl, P
4.81±1.67mg/dl, CaxP 47.2±18.3mg2 /dl2 and iPTH 277±284pg/dl. More
than 30% of patients presented serum mineral concentrations out of the
guide lines ranges; in particular 29.8% of the population showed P value
>5.5mg/dl whereas P was <3.5mg/d in 16.7% CaxP was >55 3mg2 /dl2
in the 20.9% of patients. Elevated P levels (>6.5mg/dl) and especially an
elevated CaxP (>65 mg2 /dl2 ) are associated with an increased relative risk
of CV mortality and morbidity (RR of nonfatal major CV event 1.5 and
RR of fatal CV event 1.79 respectively; P<0.05). It has to be underlined
that also low P levels (<3.5mg/dl) are associated with an increased RR of
non CV death (RR1.74; P<0.01)). Moreover patients that were in treatment
with sevelamer(n=222) showed a significant lower RR of death for CV and
non CV events (RR 2.25 for non treated patients; P<0.001)), even though
they didn’t have a better control of the mineral metabolism. (Ca 9.18±3.1
vs 9.32±3.0 p=ns; P 4.6±1.7 vs 5.5±2.0 mg/dl p=ns).
Conclusions: RISCAVID population doesn’t show an optimum control
of mineral metabolism; our data confirm the role of this disorders as an
important risk factors in ESRD. Elevated levels of P and CaxP are associated
with an increased CV risk whereas low P values are tightly related to an
increased risk of non CV death, probably due to malnutrition.
SP514 RELATIONSHIP BETWEEN CAROTID ARTERY INTIMA -
MEDIA THICKNESS AND CARDIOVASCULAR RISK
FACTORS IN CHRONIC HEMODIALYSIS PATIENTS
Hamid Reza Samimagham 1 , Hasan Mostafavi 2 . 1 Internal Medicin,
Hormozgan University of Medical Sciences, Bandar Abass, Hormozgan,
Iran; 2 Radiology, Hormozgan University of Medical Sciences, Bandar
Abass, Hormozgan, Iran
Introduction and Aims: Cardiovascular disease has been recognized for
many years to be the major cause of morbidity and mortality in ESRD
patients.Common Carotid artery intima-media thickness (CCA-IMT) corre-
lates with cardiovascular events in general population and is an independent
predictor of cardiovascular mortality in hemodialysis population.In this
investigation, we evaluated relationship between CCA-IMT and dependent
and independent cardiovascular risk factors in chronic hemodialysis patients.
Methods: Left and right CCA-IMT were measured by using high reso-
lution B- mode ultrasonography and maximum measurement was consid-
ered. Cardiovascular risk factors assessed included: history of smoking,
BMI, TG, DM, HTN, Cholesterol, LDL, and HDL. Other variables such
as,age,sex,Albumin, PTH, duration of hemodialysis, Hb and Hct, CRP were
evaluated.
Results: The 51 chronic hemodialysis patients, 31 male (60.8%), 20 female
(39.2%) with mean age 49.9±17.5 years were enrolled in this study. The
important findings in this study include: 12 pt (23.5%) had diabetes, 35
(68.8%) were hypertensive and the mean of LDL level was 112.2± 35 that
57.1% had LDL≥100,the mean right CCA-IMT was 0.65±0.17mm and
findings patients divided to two groups, one group with carotid intima
thickness ≥0.82mm [19Pts (36.6%)] and another group with carotid intima
thickness <0.82mm [32Pts (63.4%)].All obtained variables evaluated in
both groups by SPSS 13.The results showed CCA-IMT correlated to age
(P<0.05), but we could not find significant differences in other measured
variables between two groups.
Conclusions: We accept Common Carotid artery intima-media thickness
(CCA-IMT) correlates to cardiovascular events but this study indicates,
there is not significant correlation between CCA-IMT and cardiovascular
risk factors (dependent or independent) in chronic hemodialysis patients. We
recommend this study performed on larger group of chronic hemodialysis
patients.
Sunday, July 16, 2006
SP515 NICKEL AFFECTS METHIONINE CYCLE BY A
CONCENTRATION DEPENDENT MANNER AND
RESULTED IN DECREASED HOMOCYSTEINE AND
S-ADENOSYLHOMOCYSTEINE CONCENTRATION IN
VITRO AND IN VIVO
Zsuzsa Varga 1 , Istvan Karpati 1 , Sandor Biro 2 , Janos Matyus 1 ,
Laszlo Ujhelyi 1 , Lajos Papp 3 , Jozsef Posta 3 , Gyorgy Paragh 1 ,
Jozsef Balla 1 . 1 Divisions of Nephrology and Metabolism Ist. Department of
Medicine, Health and Medical Science Center University of Debrecen,
Debrecen, Hungary; 2 Department of Human Genetics, Health and Medical
Science Center University of Debrecen, Debrecen, Hungary; 3 Department
of Analytical and Inorganic Chemistry, Faculty of Science University of
Debrecen, Debrecen, Hungary
Introduction and Aims: In hemodialyis (HD) patients hyperhomocysteine-
mia is an independent risk factor for cardiovascular diseases. It is usually
treated by folic acid supplementation; however, it is inefficient at about 30%
of patients. In animals, methionin cycle, in which homocytein is formed is
modified by nickel - which is an essential element in several animal species.
It was demonstrated that nickel salt administration ameliorated hyperhomo-
cysteinemia in vitamin B12 deficient animals. However, no data about the
role of nickel in humans in this respect is available. Therefore, we studied
the possible relationship between nickel and homocysteine concentrations
in HD patients.
Methods: Trace elements, total homocysteine, vitamin B12 , and folic acid
were determined in 50 HDP and 20 controls. Three mg/day folic acid
supplementation was given to HD patients from the beginning of HD
therapy. To reveal the role of nickel in methionine-homocysteine cycle
we determined its effect on homocysteine, cysteine, S-adenosylmethionine,
S-adenosylhomocysteine, TRAIL, and Fas ligand production, cell viability,
and apoptosis in human lymphocytes.
Results: Significantly higher nickel (16.4±15.3 μg/L vs. 8.35±4.18 μg/L,
p<0.02) concentrations were found in HD patients with normal (10.±1.58
μmol/L) than high homocysteine (23.2±6.1 μmol/L) levels and this re-
lationship was independent of gender and polymorphism of C677T of
MTHFR. There were no significant differences in folic acid (29.1±22.2
vs. 24.3±19.3 μg/L) and vitamin B12 (861±675 vs. 642±425 ng/L) con-
centrations among subgroups of HD patients, and these data were in the
normal range in all cases. In human lymphocytes, nickel at its concentrations
(10-25 μg/L), observed in HD patients, significantly reduced homocysteine
(∼40%), S-adenosylhomocysteine (∼30%) and cysteine (∼20%) synthesis
without any sign of toxicity on lymphocytes, e.g. did not alter cell viability,
apoptosis, Fas ligand and TRAIL production in un-stimulated and Con-
canavalin A stimulated conditions. Nickel at those concentrations slightly
enhanced DNA methylation measured after HpaII and MspI digestion in
consequence of S-adenosylhomocysteine level reduction in cells.
Conclusions: Nickel might be an essential element in humans and is
also involved in methionine cycle by reducing homocysteine and S-
adenosylhomocysteine production. The experiment of nature, e.g. chronic
kidney disease and in vitro human lymphocyte model suggest that nickel
supplementation might be a novel tool in the treatment of hyperhomocys-
teinemia.
SP516 LOW TRIIODOTHYRONINE AND SURVIVAL IN END STAGE
RENAL DISEASE (ESRD)
Giovanni Tripepi, Francesca Mallamaci, Sebastiano Cutrupi,
Patrizia Pizzini, Carmine Zoccali. CNR-IBIM, Inst. Int. Med, Clin. Epid. &
Physiopath. of Renal Dis. and Hypert., Reggio Calabria, Italy
Introduction and Aims: Plasma triiodothyronine (fT3) is a strong predictor
of adverse clinical outcomes in various clinical conditions.
Methods: Since fT3 in patients with end stage renal diseases (ESRD) is
frequently reduced and is associated with inflammation and cardiovascular
damage, we prospectively tested the hypothesis that it predicts death in a
cohort of 200 hemodialysis patients (105 M and 95 F; age: 61 ± 15 years).
We formed two control groups: one composed by 31 healthy individuals
and an additional control group constituted by 262 clinically euthyroid
individuals with normal renal function.
Results: Plasma fT3 was significantly lower (P<0.001) in ESRD patients
(3.3±0.8 pg/mL) than in healthy subjects (3.7±1.0 pg/mL) and in clinically
Dialysis – Cardiovascular risk 1 iv189
euthyroid patients with normal renal function (3.6±0.8 pg/mL). During
the follow-up (average time: 42 months, range 0.2 to 70 months) 102
patients died. Patients who died (3.1±0.7 pg/mL) had significantly lower
plasma fT3 than those who survived (3.7±.0.8 pg/mL) (P<0.001) and in
a Kaplan-Meyer analysis plasma fT3 was strongly associated with death
(Log rank Test: 25.3, P<0.001). On multivariate Cox’s regression analyses,
adjusting for a series of traditional and emerging risk factors including
inflammation markers, patients with relatively higher plasma fT3 [hazard
ratio (HR) (1 pg/mL increase in fT3)] had a 51% reduction in the risk of
death (HR=0.49, 95% CI:0.35-0.70) as compared to those having relatively
lower fT3 levels. Of note, fT3 resulted to be a suppressor variable for IL-6
because this latter variable emerged as a significant predictor of death [HR
(10 pg/mL increase): 1.28, 95% CI: 1.04-1.58] only in a model excluding
fT3, a phenomenon suggesting that low fT3 captures part of the predictive
power of IL-6.
Conclusions: Low fT3 is an independent predictor of death in hemodialysis
patients. These data lend support to the hypothesis that thyroid dysfunction
is implicated in the high risk of the ESRD population.
SP517 LEFT VENTRICULAR HYPERTROPHY IN HEMODIALYSIS
PATIENTS – CORRELATION WITH CARDIAC TROPONINS
Dejan Petrovic, Radmila Obrenovic, Milan Radovanovic,
Nada Majkic-Singh, Biljana Stojimirovic. Department of Hemodialysis, KC
Kragujevac, Kragujevac, Serbia, Serbia/Montenegro; Department of
Biochemistry, Institute of Medical Biochemistry, Belgrade, Serbia,
Serbia/Montenegro; Emergency Center, KC Kragujevac, Kragujevac,
Serbia, Serbia/Montenegro; Department of Biochemistry, Institute of
Medical Biochemistry, Belgrade, Serbia, Serbia/Montenegro; Clinic of
Nephrology, Institute of Urology and Nephrology, Belgrade, Serbia,
Serbia/Montenegro
Introduction and Aims: Cardiovascular diseases are the most frequent
cause of death among hemodialysis patients. Left ventricular hypertrophy
is a potent predictor of cardiovascular morbidity and mortality in those
patients. Cardiac troponins (cTnT and cTnI) are indices of myocardial
cell damage. Aim of the paper was to investigate relationship between
serum troponins T and I concentrations and echocardiographic parameters
in estimation of left ventricular hypertrophy and dilatation, ischemic heart
disease and left ventricular systolic function.
Methods: The study included 115 patients (71 men and 44 women) with
mean age of 53.30 ± 12.17 years. Mean troponin T serum value was
0.14 ± 0.23 ng/mL, troponin I 0.20 ± 0.48 ng/mL, thickness of posterior
wall in diastole-PWLVd 11.44 ± 2.09 mm, thickness of interventricular
septum in diastole-IVSd 11.21 ± 2.12, index of end-diastolic left ventricular
volume-iEDV 100.80 ± 34.62 mL/m2 and left ventricular mass index-LVMi
143.85 ± 41.21 g/m2 .
Results: There is a statistically significant positive correlation among serum
troponine T concentration, thickness of interventricular septum in diastole-
IVSd, thickness of left ventricular posterior wall in diastole-PWLVd and
index of end-diastolic left ventricular volume-iEDV. A highly significant
positive correlation was found between serum troponin T concentration and
left ventricular mass index-LVMi.
Conclusions: Troponin T represents a good marker of left ventricular wall
thikness in hemodialysis patients.
SP518 LOW MOLECULAR THIOLS, PRO-COAGULANT STATE
AND NATURAL ANTIOXIDANT SYSTEM IN HEMODIALYSIS
PATIENTS
Amelia Bernasconi 1 , Fabiana Alberto 2 , Mariela Hendler 2 ,
Susana Meschengieser 2 , Marta Lazzari 2 , Nelida Correa 1 , Andres Liste 1 ,
Ricardo Heguilen 1 . 1 Division of Nephrology, Hospital Juan A Fernandez,
Buenos Aires, Argentina; 2 Department of Homeostasia and Thrombosis,
Academia Nacional de Medicina, Buenos Aires, Argentina
Introduction and Aims: Cardiovascular disease is the major cause of
mortality in patients receiving hemodialysis (HD). Hyperhomocysteinemia,
high levels of procoagulant marker D-dimer (DD) and deficiencies in
natural antioxidant systems as erythrocyte glutathione (GSHe) and plasma
glutathione peroxidase (Gpx-3) have been associated with vascular occlusive
iv190 Dialysis – Cardiovascular mortality 1
disease. The aim of the present study was to investigate the effect of HD on
total homocysteine (Hcy), total cysteine (Cys), DD level, GSHe and Gpx-3
activity.
Methods: Twenty one bicarbonate-buffered HD Pts (9 male) aged 52.1
± 3.1 years entered the study. Hcy, Cys, GSHe (total concentrations by
HPLC); DD (Vidas System); Gpx-3 (Randox); urea; creatinine and albumin
were measured before and after a single regular 4-h HD session performed
through a permanent arterio-venous fistula.
Results: HD decreased Hcy (22.8 ± 1.1 to 18.6 ± 1.1 μmol/L p< 0.001)
and Cys from 493.1 ± 20.6 to 283 ± 14.8 μmol/L (p < 0.001). There was a
correlation between Hcys and Cys (r= 0.52; p= 0.018) only after HD. Before
HD 67% of Pts had DD over cut-off value (500 nmol/L), there wasn’t any
difference in pre-post HD DD values; DD only correlated inversely with
albumin (r= -0.76; p< 0.01). No differences in pre-pos HD GSHe level
were found, only post HD GSHe (7.13 ± 1.54 umol/g Hb) was diminished
compared to a control group (n= 31, 8.09 ± 1.37 umol/g Hb, p=0.02).
Pre HD Gpx-3 (0.23 ± 0.05 UI/ml) was diminished compared to a control
group (n= 15, 0.56 ± 1.27 UI/ml p<0.0001) but no differences in pre-pos
HD Gpx-3 activities were found.
Conclusions: HD produces a more pronounced reduction in Cys than Hcys.
Cys is a critical substrate in biosynthesis of protein and GSH. HD diminished
GSHe and raises the question whether CYS should be supplemented in
ESRD. A prothrombotic condition was determined in most however DD
levels were not modified by HD. All the participants have low activity of
Gpx3 and reduction was found after HD but is clear that supplementations
of vitamins possessing antioxidant effect are necessary.
Dialysis – Cardiovascular mortality 1
SP519 THE IMPACT OF CARVEDILOL ON HEMODYNAMIC AND
ENDOTHELIAL VASCULAR FUNCTION IN HEMODIALYSIS
PATIENTS WITH HYPERTENSION
W.J. Haykal, O.V. Kuryata. Hospital Therapy #1, Centre of Haemodialysis,
Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine
Introduction and Aims: Cardiovascular disease (CVD) is the major cause
of death among patients with end-stage renal disease (ESRD). Hemodialysis
(HD) patients have many of the traditional “Framingham” risk factors for
CVD, but in addition suffer from a lot of nontraditional risk factors that
are relatively unique to kidney disease. Endothelial Dysfunction (ED) is the
earliest measurable functional abnormality of the vessel wall.
The aim of this study was to identify the clinical and functional effects of
carvedilol, focusing on hemodynamic and endothelial vascular function in
HD patients with hypertension (HTN).
Methods: 42 HD patients with HTN (26 M, 16 F; mean age 41,4±5,2
years, mean time on HD 28,3±4,3 months, mean blood pressure (BP)
level 153,2±5,2/104,3±7,2 mm Hg, mean heart rate (HR) level 76,3±3,2
bt/min, left ventricular ejection fraction (LVEF) > 45%) were treated with
carvedilol (mean dose 28,4±2,5 mg/day). LV end-diastolic and end-systolic
volumes and dimensions (LVEDV), (LVESV), (LVEDD), (LVESD), LV
ejection fraction (LVEF), LV myocardial mass (LVMM) and LVMM index
(LVMMI) were performed with an ultrasound system by using M,B, 2D,
CFM and PW- mode with 3,5 MHZ transducers. Endothelial function was
assessed by measuring flow-mediated dilation (FMD) in the brachial artery
using 2D, CFM Color Doppler with 5-12 MHZ transducers. Clinical and
echocardiographic variables were measured at baseline and after 6 months
of treatment and the results compared.
Results: All patients finished the study. At week 24 35(83,33%) patients
achieved the BP goal attainment of ≤ 130/80 mm Hg. Mean systolic
BP, diastolic BP and HR levels had decreased by 16,25%, 26,74%, and
10,22% respectively. Patients demonstrated improvement in clinical features
and general state. LVEF had increased by 8,47%; this change was caused
by a reduction in LVEDD, LVESD, LVEDV, LVESV, and LVMM by
17,06%, 11,16%, 15,10%, 10,60% and 10,84% respectively [table 1].
Decreased BP was associated with decreased LVMMI (r = 0,43, p < 0,001).
FMD was significantly impaired in 61(80,26%) patients (FMD < 10%
during reactive hyperemia). Percent diameter variation 4,4±1,2%. Among
them 25(32,89%) patients had paradoxical vasoconstrictive reaction during
Sunday, July 16, 2006
reactive hyperemia, which implicates severe ED. At week 24 the FMD had
enhanced by 86,36% (p < 0,001) and normalized in 16(38,09%) patients.
The improvement in FMD was closely correlated with decreased systolic
and diastolic BP and LVMMI levels (r = -0,33, p < 0,01; r = -0,48, p <
0,01; and r = - 0,58, p < 0,01 respectively). The most improvement was in
patients with baseline paradoxical vasoconstrictive reaction.
Conclusions: Long-term carvedilol therapy in HD patients with hyperten-
sion was able to prevent or partially reverse progressive left ventricular
hypertrophy. The effects on left ventricular remodeling were associated with
a concomitant improvement in endothelial vascular function, which may
be powerful prognostic predictors of cardiovascular events in such patients.
Carvedilol provides benefits for the reduction of cardiovascular risk and
must be used for the management of hypertension in patients on HD.
SP520 THE EFFECTS OF SIMVASTATIN ON RESPONSE TO BETA
EPOETIN TREATMENT AND OTHER CARDIOVASCULAR
RISK FACTORS IN HAEMODIALYSIS PATIENTS
Wahib J. Haykal, Olexandr V. Kuryata, Ghadir M. Allaou. Hospital
Therapy #1, Centre of Haemodialysis, Dnepropetrovsk State Medical
Academy, Dnepropetrovsk, Ukraine
Introduction and Aims: Erythropoiesis-stimulating agents (ESA) are used
for treatment of renal anaemia in haemodialysis patients, and have a
major impact on the quality of life of these patients, reducing fatigue and
increasing exercise capacity. However, chronic inflammation, caused by
uraemia and dialysis, is known to be associated with anaemia, and can
reduce responsiveness to ESA therapy.
Accordingly, the aim of this study was to estimate the effects of simvastatin
on response to Beta Epoetin (recormon) and inflammation, focusing on the
haemoglobin level, C-reactive protein and endothelial vascular function in
haemodialysis patients.
Methods: 33 patients with haemoglobin (Hb) < 110g|L with ESRD on
haemodialysis (HD) [18 M, 15 F; mean age 38,42±5,51 years, mean
time on HD 28,12±3,43 months, mean Hb level 93,33±2,23 g/L, blood
pressure 133,23±5,43/72,31±3,22 mm Hg] were enrolled. These patients
were divided into 2 groups: gr.I 15(45,45%) patients with Hb 93,45±4,21
g|L received both Beta Epoetin and low-dose simvastatin 10 mg/day; gr.II
18(54,54%) patients with Hb 93,38±3,67 g|L received only Beta Epoetin.
Beta Epoetin titrated accordingly to guidelines and administered IV 3
times weekly after haemodialysis session. The high-sensitive C-reactive
protein (hs-CRP), as an inflammatory marker and endothelial-independent
vasodilatation (EIV) assessed by the % change of flow from baseline to the
maximum flow during reactive hyperemia were determined at baseline and
after treatment at week 24.
Results: Hs-CRP was increased in all patients and correlated with Hb
level (r=-0,45, p<0,05). The mean hs-CRP was 22,3±1,8 mg/L in gr.I
and 21,8±1,3 mg/L in gr.II. All patients had endothelial dysfunction. The
flow-mediated dilation (FMD) correlated with high hs-CRP and low Hb
levels (r= -0,38, p<0,01 and r= 0,38, p<0,005 respectively). All patients
finished the study. After 6 months of therapy 13(86,66%) patients in gr.I
and 12(66,66%) patients in gr.II had been achieved the Hb target goal >120
g/L. At week 24 Hb level had been increased in gr.I and gr.II by 30% and
15% respectively in comparison with baseline. Evidence of difference in
increasing Hb level between groups was observed at week 8 and simvastatin
reached maximum actions by week 12. In gr.I – the mean dose of Beta
Epoetin was 8300 IU/week, since in gr. II – 12200 IU/week. Hs-CRP
decreased by 68% in gr.I and 8% in gr.II at week 24. The dose adjustment
of Recormon correlated with hs-CRP level (r=0,38, p<0,01). The EIV had
been improved by 22% and normalized in 18% of cases in gr.I, however
no significant changes were matched in gr.II. The improvement of EIV was
significantly noted in patients with baseline lower Hb level.
Conclusions: Beta Epoetin is effective and safe for the management
of anaemia in haemodialysis patients. However, the synergistic actions
of simvastatin and Beta Epoetin improve the ESA hyporesponsiveness
or suppress EPO resistance upon decreasing inflammation that may be
beneficial for this population.