This study examined the relationship between volume overhydration and endothelial dysfunction in 81 stable patients on continuous ambulatory peritoneal dialysis. Volume status was assessed by normalized extracellular water and endothelial function was estimated by flow-mediated dilation of the brachial artery. There was an independent correlation between the index of volume status (normalized extracellular water) and endothelial function (flow-mediated dilation), with higher normalized extracellular water related to worse endothelial function. Multiple regression analysis identified calcium-phosphate product, normalized extracellular water, and dialysis vintage as independent determinants of endothelial function. The results suggest that volume overhydration may lead to increased cardiovascular risk in dialysis patients through its effects on endothelial dysfunction.
2. 398
CHENG et al. JULY 2008 – VOL. 28, NO. 4 PDI
functionally significant coronary artery disease (11). As
a result, patients were divided into two groups based on
FMD: normal group, FMD ≥ 10%; abnormal FMD group,
FMD < 10%.
MEASUREMENT OF BLOOD PRESSURE
Adedicatedrenalnursewasinchargeofallbloodpres-
sure measurements and performed measurements under
strict instruction but was not aware of the study proto-
col or objective. The mercury sphygmomanometer used
was calibrated regularly. The patients were asked to take
their usual antihypertensive medications, given the pos-
sibly dangerous outcome for abrupt withdrawal of anti-
hypertensive medications. However,they were asked not
to take breakfast because fasting plasma was tobe taken
for biochemical examination. All measurements were
performed in a quiet room. Brachial blood pressure was
measured twice in sitting position after patients had
rested more than 10 minutes. Phases I and V of the
Korotkoff sounds were taken as systolic blood pressure
(SBP) and diastolic blood pressure (DBP) respectively.
Both SBP and DBP were averaged from values of the two
measurements.
Antihypertensive drugs were divided into six catego-
ries: diuretic, β-blocker,calciumchannelblocker, angio-
tensin-converting enzyme inhibitor, angiotensin II
receptor I blocker, and α-receptor antagonist. Doses of
antihypertensive drugs were calculated according to the
standard of defined daily dose recommended by the
World Health Organization (12).
MEASUREMENT OF BIOCHEMICAL PARAMETERS AND DIALYSIS
ADEQUACY
Serum albumin was determined by the bromcresol
green method. High-sensitivity C-reactive protein
(hs-CRP) was measured as inflammatory index; the cut-
off value is 3 mg/L in our hospital’s laboratory. Other
biochemical indices, such as blood urea nitrogen, serum
creatinine, calcium, and phosphate were determined
using standard methods. Residual renal function was
measured as glomerular filtration rate using the mean
of urea and creatinine clearances. A dialysis dose was
measured by instilled dialysate volume and average
glucose exposure, which was calculated as the instilled
dialysate volume times the respective glucose concen-
tration. Small solute removal was determined by mea-
surement of total (peritoneal dialysis and renal) weekly
urea Kt/V using standard methods (13). The contribu-
tions to total Kt/V (tKt/V) by peritoneal dialysis (pKt/V)
and residual renal function (rKt/V) were estimated sepa-
less than 3 months; (2) congestive heart failure (NYHA
class III to IV); and (3) not able to provide written in-
formed consent. This study was performed from 6 to 30
November 2006; all patients that visited our outpatient
clinics during this period were considered eligible can-
didates of this study. We had around 30 patients visiting
our outpatient clinics per week during our study; all pa-
tients that did not meet the exclusion criteria (n = 105)
were invited to take part in the present study. Twenty-
four patients (22.8%) refused evaluation due to various
reasons (no interest, time limitation, etc.). As a result,
81patientswereincludedintothisstudy.Theethicscom-
mittee approved this study protocol.
BIOIMPEDANCE ANALYSIS
Multiple-frequency bioelectrical impedance analysis
was performed using the Hydra analyzer (Xitron Tech-
nologies, San Diego, California, USA). The procedure to
perform this measurement has been described in detail
elsewhere (10). Briefly, after the patient takes the su-
pinepositionforatleast10minutes,standardtetrapolar
electrodes are placed on the dorsum of the wrist and the
anterior aspect of the ankle on the left side of the body.
Three consecutive measurements are performed over a
2-minuteperiod,recordingvaluesforextracellularwater
(ECW), intracellular water, and total body water. In the
presentstudy,ECWwasnormalizedtopatients’individual
heights in meters (nECW) (1).
FLOW-MEDIATED DILATATION
Endothelium-dependentresponsesweremeasuredfor
each adult after dialysates were emptied. After the sub-
ject had been lying supine on a couch for 10 minutes,
the right brachial artery was imaged in longitudinal sec-
tion between 10 and 15 cm above the antecubital fossa
using a 7-MHz linear array transducer and a standard
Acuson128XP/10system(Siemens,Erlangen,Germany).
Baseline brachial artery diameter was measured using
an automated wall tracking system (Sonoline G50;
Siemens) that utilizes movement in the radio frequency
amplitude peaks over the cardiac cycle to identify the
arterial walls (8,9). A pneumatic cuff was then inflated
to suprasystolic pressure on the forearm for 5 minutes
to induce a reactive hyperemia. Cuff deflation resulted
in increased flow through the brachial artery, stimulat-
ing endothelial-dependent FMD. The change in brachial
artery diameter 1 minute after cuff release was mea-
sured. In this study, 10% was chosen as the cutoff value
for FMD because a 10% cutoff value was shown to have
91% sensitivity and 95% negative predictive value for
byguestonApril24,2014http://www.pdiconnect.com/Downloadedfrom
3. 399
PDI JULY 2008 – VOL. 28, NO. 4 VOLUME OVERHYDRATION AND ENDOTHELIAL DYSFUNCTION IN PD
rately. The volume of urea distribution (V) was derived
using Watson’s formula (14).
STATISTICAL ANALYSIS
Statistical analysis was performed using SPSS soft-
ware, version 11.0 (SPSS Inc., Chicago, Illinois, USA).
Continuous variables are expressed as mean ± SD while
categorical variables are expressed as percentage. In-
dependent t-test was used for continuous variables nor-
mally distributed in two-group comparison, while
Mann–Whitney’s test was used for non-normally distrib-
uted variables, such as hs-CRP and dialysis vintage. For
comparison of categorical variables in two groups, such
astheproportionofdiabeticsorgenderdistribution,chi-
square test was employed. Pearson’s correlation analy-
sis was performed to explore the possible relationship
between FMD and other continuous variables. The sig-
nificant variables identified by Pearson’s correlation
analyses were further selected into a multiple regression
model to determine whether they could still indepen-
dently affect FMD (stepwise method). All tests were two-
sided and p < 0.05 was considered to be statistically
significant.
RESULTS
DEMOGRAPHIC DATA OF THE STUDY POPULATION
The demographic data of the study population are
shown in Table 1. Of the 81 patients, 55% were male,
mean age was 61 years, mean height and weight were
159 ± 8 cm and 59 ± 10 kg respectively. At the time stud-
ied, dialysis vintage was 20 ± 23 months. Primary diag-
noses were chronic glomerulonephritis (20%), diabetes
mellitus (26%), hypertension (16%), interstitial nephri-
tis (16%), and unknown causes (21%). In total, 67.9%
of patients were on antihypertensive medication, while
calciumchannelblocker,angiotensin-convertingenzyme
inhibitor/angiotensin II receptor I blocker, and
β-blocker were the most frequently prescribed drugs.
COMPARISON OF VARIABLES BETWEEN NORMAL FMD GROUP
AND ABNORMAL FMD GROUP
Comparisons of various parameters between the nor-
mal FMD group and the abnormal FMD group are shown
in Table 2. There were 20 (25%) and 61 (75%) patients
divided into normal FMD group and abnormal FMD group
respectively. There was no significant difference in age
between the two groups; however, there were more male
(54.1% vs 20%, p < 0.01) and diabetic (37.7% vs 15%,
p = 0.059) patients in the abnormal FMD group. High-
sensitivity CRP and nECW were also higher in abnormal
FMD group compared with normal FMD group (p < 0.05
and p < 0.001 respectively). Phosphate and the product
of phosphate times calcium (Ca×P) were significantly
higher in normal FMD group compared with abnormal
FMD group (bothp< 0.05). There were no significant dif-
ferences in plasma sodium concentration, glomerular
filtration rate, SBP, DBP, defined daily dose, instilled di-
alysate volume, average glucose exposure, dialysate-to-
plasmaratioofcreatinine,rKt/V,pKt/V,ortKt/Vbetween
the two groups.
CORRELATION AND REGRESSION ANALYSIS
Pearson’s correlation analysis between FMD and other
variables is shown in Table 3. Negative correlation was
found between FMD and weight, body mass index, SBP
(r = –0.228, p < 0.05), and nECW (r = –0.418, p < 0.001).
Marginal positive correlation between FMD and Ca×P was
observed (r = 0.192, p = 0.086). No correlation was ob-
served between FMD and age, hs-CRP, calcium, phos-
phate, glomerular filtration rate, rKt/V, pKt/V, or tKt/V.
Associations between FMD and other variables were
further assessed using a multivariable-adjusted regres-
sion model (Table 4). In this model, a number of vari-
ables possibly affecting FMD were selected, such as
TABLE 1
Demographic Characteristics of the
Study Population (mean±SD)
Patients (n) 81
Male 55%
Age 61±12 years
Height 159±8 cm
Weight 59±10 kg
Body mass index 24±3 kg/m2
Dialysis vintage 20±23 months
Primary diagnosis
Chronicglomerulonephritis 20%
Diabetes mellitus 26%
Hypertension 16%
Interstitialnephritis 16%
Unknown 21%
Antihypertensivemedication 67.9%
ACEI/ARB 38.3%
Beta-blocker 28.4%
Calcium channel blocker 46.9%
Diuretic 0%
Others 2.5%
ACEI = angiotensin-converting enzyme inhibitor; ARB = an-
giotensin II receptor blocker.
byguestonApril24,2014http://www.pdiconnect.com/Downloadedfrom
4. 400
CHENG et al. JULY 2008 – VOL. 28, NO. 4 PDI
gender (female = 1, male = 0), age, body mass index,
dialysis vintage (log transformed), antihypertensive
medication (yes = 1, no = 0), Ca×P, triglycerides, total
cholesterol levels, high-density lipoprotein cholesterol,
low-density lipoprotein cholesterol, hs-CRP (log trans-
formed),rKt/V,pKt/V,andtKt/V.Theresultsshowedthat
only Ca×P (β = 0.422, p < 0.001), nECW (β = –0.343, p <
0.01), and dialysis vintage (β = –0.237, p < 0.05) were
independent determinants of FMD (adjusted R2 = 0.327
for this model).
DISCUSSION
Although concerns with volume overhydration have
beenincreasinginrecentyears,littleisknownabouthow
volume overhydration imposes its detrimental effect on
the cardiovascular system, especially at the vascular
level. Because it is noninvasive and reflects nitric oxide
availability,FMDisanappropriatemethodtostudyendo-
thelial function in humans (15). Its noninvasive nature
is a major advantage of FMD, contributing to its wide use
in evaluating endothelial dysfunction in various clinical
studies.
Flow-mediated vasodilatation was employed in the
present study. We were able to show that the index of
volume status, nECW, was correlated with FMD in
81 stable patients on continuous ambulatory peritoneal
dialysis (CAPD). After adjusting for a number of con-
founding factors, nECW, together with Ca×P and dialysis
vintage, were independent determinants of FMD in this
population. To the best of our knowledge, this study is
the first to show such a close relationship between vol-
ume status and FMD in dialysis patients.
The underlying mechanism of this close correlation
between nECW and FMD revealed in the present study
remains speculative. First, volume overhydration may
compromise FMD through increased shear stress. It has
been documented that the FMD in essential hyperten-
sive subjects is significantly impaired compared with
normotensive controls (16–18), usually attributed to
increased shear stress in this population. Therefore, the
indirect effect of volume overhydration on FMD is sus-
pected, given the well-recognized contribution of vol-
ume overload to the pathogenesis of hypertension in
dialysis patients (3,19). However, neither SBP nor DBP
in this study turned out to be a significant determinant
ofFMDinmultipleregressionanalysis(Table4),suggest-
TABLE 2
Comparison of Various Parameters Between Normal Flow-
Mediated Dilatation (FMD) Group (FMD≥10%) and
Abnormal FMD Group (FMD<10%)
FMD group
Normal Abnormal
(n=20) (n=61) p Value
Age (years) 63±11 60±12 NS
Male 20% 54.1% <0.01
Diabetic 15% 37.7% NS
hs-CRP(mg/L) 3.5±5.5 11.0±35.6 <0.05
nECW (L/m) 8.08±1.15 9.86±2.01 <0.001
Ca×P (mmol2/L2) 3.95±1.10 3.29±0.89 <0.01
Phosphate(mmol/L) 1.75±0.38 1.53±0.36 <0.05
Calcium (mmol/L) 2.23±0.25 2.16±0.33 NS
Plasma sodium (mmol/L) 140.3±3.0 138.1±3.5 NS
GFR (mL/min) 2.17±1.89 2.15±1.43 NS
Systolic BP (mmHg) 138±19 143±27 NS
Diastolic BP (mmHg) 79±12 83±12 NS
Defined daily dose 1.88±1.32 2.46±1.64 NS
Instilled dialysate (mL/day) 5450±2186 5715±1971 NS
Glucose exposure (g/day) 106.9±29.9 107.8±40.8 NS
D/P creatinine 0.71±0.10 0.75±0.15 NS
Renal Kt/V 0.54±0.47 0.63±0.81 NS
Peritoneal Kt/V 1.31±0.75 1.36±0.49 NS
Total Kt/V 1.88±0.49 1.99±0.68 NS
hs-CRP = high-sensitivity C-reactive protein; nECW = extracel-
lularwaternormalizedtopatientheight;Ca×P=calcium–phos-
phate product; GFR = glomerular filtration rate; BP = blood
pressure; D/P creatinine = dialysate-to-plasma creatinine
ratio.
TABLE 3
Pearson’s Correlation Analysis Between Flow-Mediated
Dilation Index and Other Variables
Variable Coefficient of correlation p Value
Age 0.123 NS
hs-CRP –0.036 NS
Dialysis vintage –0.136 NS
Height –0.201 NS
Weight –0.308 <0.01
Body mass index –0.242 <0.05
Systolic BP –0.228 <0.05
Diastolic BP –0.139 NS
Defined daily dose –0.183 NS
nECW –0.418 <0.001
Calcium 0.136 NS
Phosphate 0.12 NS
Ca×P 0.192 NS
Plasma sodium 0.152 NS
GFR –0.095 NS
hs-CRP = high-sensitivity C-reactive protein; BP = blood pres-
sure;nECW=extracellularwaternormalizedtopatientheight;
Ca×P = calcium–phosphate product; GFR = glomerular filtra-
tion rate.
byguestonApril24,2014http://www.pdiconnect.com/Downloadedfrom
5. 401
PDI JULY 2008 – VOL. 28, NO. 4 VOLUME OVERHYDRATION AND ENDOTHELIAL DYSFUNCTION IN PD
ing that other mechanisms between volume over-
hydration and FMD should be considered. Second, vol-
ume overhydration may impair FMD through its close
association with inflammation. It is known that volume
overhydration may lead to inflammation through in-
creased permeability of the gastrointestinal tract, which
consequently leads to bacteria or endotoxin transloca-
tion and hence inflammation (20,21). At the same time,
it is known that inflammation is related to endothelial
dysfunction in dialysis patients (22,23). In the present
study, hs-CRP was shown to have a negative correlation
with FMD, which seems to provide some support to this
speculation.However,thelaterregressionanalysisfailed
to show any independent relationship between the two
variables after adjusting for other confounding factors.
Further study is needed to provide a more satisfactory
answer.
This study also revealed that Ca×P is positively corre-
lated with FMD in dialysis patients, which is not com-
pletely consistent with previous reports. In one study,
FMD was shown to be impaired in patients with primary
hyperparathyroidism compared with controls (24); this
conclusion was not confirmed in another study per-
formed in hypocalcemic subjects (25). In patients with
chronickidneydisease,Bortotolottoetal.foundthatthe
product of Ca×P had no effect on FMD (26). DOQI guide-
lines recommended that the Ca×P product should be
maintained at <55 mg2/dL2 (<4.4 mmol2/L2) (27). We
rechecked our data and found that 11 of 81 patients
(13.6%) were abnormal according to this recommenda-
tion (6 in the normal FMD group and 5 in the abnormal
FMD group, or 8.2% vs 30%; p< 0.05 by chi-square test).
In other words, what we studied here was a population
dominated by “normal” Ca×P values. Within normal
range, a higher Ca×P product may reflect a better nutri-
tional status, which might serve as a confounding fac-
tor in this paradoxical relationship. On the other hand,
astatisticalerrorcouldnotbecompletelyruledoutgiven
theobvioussmallersamplesizeofthenormalFMDgroup.
We believe further prospective study is warranted in this
field to provide a more definite answer.
There were some limitations in the present study.
First, the cross-sectional design and the consequent
descriptivenatureofthisstudylimitedourabilitytoinfer
a causal relationship between nECW and FMD. Second,
although a number of potential confounding factors,
such as sex, age, body mass index, diabetes, lipid pro-
file, antihypertensive medication, and indices of dialy-
sis adequacy, were controlled in multiple regression
analysis, the existence of unrecognized confounding
variables was always possible. Therefore, the observed
results in this study should be further validated in fu-
ture prospective studies.
In conclusion, this study showed that nECW is associ-
ated with FMD in CAPD patients. In addition, nECW, to-
gether with Ca×P and dialysis vintage, were independent
determinants of FMD in CAPD patients, suggesting that
endothelial dysfunction might be the link between vol-
ume overhydration and cardiovascular events and mor-
tality in dialysis patients.
ACKNOWLEDGMENTS
Thisstudywaspartlysupportedbyagrant(36-1)fromCheung
Kong Scholar Programme, Ministry of Education, People’s Re-
public of China.
The authors thank all the staff in the Division of Nephrol-
ogy, Peritoneal Dialysis Center, Peking University Third
Hospital.
REFERENCES
1. Konings CJ, Kooman JP, Schonck M, Struijk DG, Gladziwa
U, Hoorntje SJ, et al. Fluid status in CAPD patients is re-
latedtoperitonealtransportandresidualrenalfunction:
evidencefromalongitudinalstudy.NephrolDialTransplant
2003; 18:797–803.
2. LinYP,ChenCH,YuWC,HsuTL,DingPY,YangWC.Leftven-
tricularmassandhemodynamicoverloadinnormotensive
TABLE 4
Output from Multivariate Linear Regression Model Predicting Flow-Mediated Dilatation Index in 81 CAPD Patients
Variable Beta 95% CI p Value Adjusted R2
Ca×P 0.442 1.168 to 3.806 <0.001 0.193
nECW –0.343 –1.637 to –0.321 <0.01 0.284
Dialysis vintage –0.237 –0.113 to –0.001 <0.05 0.327
Ca×P = calcium–phosphate product; nECW = extracellular water normalized to patient height; CI = confidence interval.
The original model included all variables significantly associated with flow-mediated dilatation in univariate analysis (weight,
body mass index, systolic blood pressure, ECW, nECW, high-sensitivity C-reactive protein, gender, and antihypertensive medica-
tion). The whole model R2 = 0.327.
byguestonApril24,2014http://www.pdiconnect.com/Downloadedfrom
6. 402
CHENG et al. JULY 2008 – VOL. 28, NO. 4 PDI
hemodialysis patients. Kidney Int 2002; 62:1828–38.
3. WangMC,TsengCC,TsaiWC,HuangJJ.Bloodpressureand
leftventricularhypertrophyinpatientsondifferentperi-
toneal dialysis regimens. Perit Dial Int 2001; 21:36–42.
4. Konings CJ, Kooman JP, Schonck M, Dammers R, Cheriex
E, Palmans Meulemans AP, et al. Fluid status, blood pres-
sure,andcardiovascularabnormalitiesinpatientsonperi-
toneal dialysis. Perit Dial Int 2002; 22:477–87.
5. LameireN,VanBW.Importanceofbloodpressureandvol-
ume control in peritoneal dialysis patients. Perit Dial Int
2001; 21:206–11.
6. LandmesserU,DrexlerH.Theclinicalsignificanceofendo-
thelial dysfunction. Curr Opin Cardiol 2005; 20:547–51.
7. AndersonEA,MarkAL.Flow-mediatedandreflexchanges
in large peripheral artery tone in humans. Circulation
1989; 79:93–100.
8. CelermajerDS,SorensenKE,GoochVM,SpiegelhalterDJ,
Miller OI, Sullivan ID, et al. Non-invasive detection of
endothelial dysfunction in children and adults at risk of
atherosclerosis. Lancet 1992; 340:1111–15.
9. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D,
Charbonneau F, Creager MA, et al. Guidelines for the ul-
trasound assessment of endothelial-dependent flow-
mediated vasodilation of the brachial artery: a report of
the International Brachial Artery Reactivity Task Force.
J Am Coll Cardiol 2002; 39:257–65.
10. Davies SJ, Woodrow G, Donovan K, Plum J, Williams P,
Johansson AC, et al. Icodextrin improves the fluid status
of peritoneal dialysis patients: results of a double-blind
randomized controlled trial. J Am Soc Nephrol 2003; 14:
2338–44.
11. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Rand WM,
Udelson JE, et al. Peripheral vascular endothelial func-
tiontestingasanoninvasiveindicatorofcoronaryartery
disease. J Am Coll Cardiol 2001; 38:1843–9.
12. Lunde P, Baksaas I, Halse M, Strommes B, Aeydvin K. The
methodology of drug utilization studies. In: Bergman U,
Grimsson A, Wahba AHW, Werterholm B, eds. Studies in
Drug Utilization. Copenhagen: WHO Regional Office for
Europe; 1979: 17–28.
13. Nolph KD, Moore HL, Prowant B, Meyer M, Twardowski ZJ,
KhannaR,etal.Cross-sectionalassessmentofweeklyurea
and creatinine clearance and indices of nutrition in con-
tinuousambulatoryperitonealdialysispatients.PeritDial
Int 1993; 13:178–83.
14. Watson P, Watson I, Batt R. Total body water volumes for
adult males and females estimated from simple anthro-
pometric measurements. Am J Clin Nutr 1980; 33:27–39.
15. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH,
Thuillez C, et al. Nitric oxide is responsible for flow-de-
pendent dilatation of human peripheral conduit arteries
in vivo. Circulation 1995; 91:1314–19.
16. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal
endothelium-dependent vascular relaxation in patients
withessentialhypertension.NEnglJMed1990;323:22–7.
17. GhiadoniL,TaddeiS,VirdisA,SudanoI,DiLeggeV,Meola
M, et al. Endothelial function and common carotid artery
wall thickening in patients with essential hypertension.
Hypertension 1998; 32:25–32.
18. Muiesan ML, Salvetti M, Monteduro C, Corbellini C, Guelfi
D, Rizzoni D, et al. Flow-mediated dilatation of the bra-
chial artery and left ventricular geometry in hyperten-
sive patients. J Hypertens 2001; 19:641–7.
19. Lins RL, Elseviers M, Rogiers P, Van Hoeyweghen RJ,
DeRaedtH,ZacheeP, et al. Importanceofvolumefactors
in dialysis related hypertension. Clin Nephrol 1997; 48:
29–33.
20. AguileraA,CodoceoR,SelgasR,GarciaP,PicornellM,Diaz
C, et al. Anorexigen (TNF-alpha, cholecystokinin) and
orexigen(neuropeptideY)plasmalevelsinperitonealdi-
alysis (PD) patients: their relationship with nutritional
parameters. Nephrol Dial Transplant 1998; 13:1476–83.
21. Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann
RR,RauchhausM,etal.Endotoxinandimmuneactivation
in chronic heart failure: a prospective cohort study.
Lancet 1999; 353:1838–42.
22. Dogra G, Irish A, Chan D, Watts G. Insulin resistance, in-
flammation, and blood pressure determine vascular dys-
function in CKD. Am J Kidney Dis 2006; 48:926–34.
23. Yilmaz MI, Saglam M, Carrero JJ, Qureshi AR, Caglar K,
Eyileten T, et al. Serum visfatin concentration and endo-
thelialdysfunctioninchronickidneydisease.NephrolDial
Transplant 2008; 23:959–65.
24. Kosch M, Hausberg M, Vormbrock K, Kisters K, Rahn KH,
BarenbrockM.Studiesonflow-mediatedvasodilationand
intima-media thickness of the brachial artery in patients
withprimaryhyperparathyroidism.Am J Hypertens2000;
13:759–64.
25. Neunteufl T, Katzenschlager R, Abela C, Kostner K,
NiederleB,WeidingerF,etal.Impairmentofendothelium-
independentvasodilationinpatientswithhypercalcemia.
Cardiovasc Res 1998; 40:396–401.
26. Bortotolotto LA, Costa-Hong V, Jorgetti V, Consolim-
Colombo F, Rosa K, Silva BC, et al. Vascular changes in
chronic renal disease patients with secondary hyperpar-
athyroidism. J Nephrol 2007; 20:66–72.
27. Block GA, Port FK. Re-evaluation of risks associated with
hyperphosphatemia and hyperparathyroidism in dialysis
patients:recommendationsforachangeinmanagement.
Am J Kidney Dis 2000; 35:1226–37.
byguestonApril24,2014http://www.pdiconnect.com/Downloadedfrom
