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withdrawn. Paradoxically, the more med-ications the patients received, the morelikely they were to be hypertensive.

Epidemiology of Hypertension inPeritoneal Dialysis

Some studies suggest that hypertensioncontrol in patients on peritoneal dialysis(PD) is superior compared with those onHD.9,10 For example, among 1202 pa-

tients participating in the 1995 Perito-neal Dialysis Core Indicators Study, theaverage BP among PD patients was 139/80 mmHg.11 This is in contrast with thepredialysis BP of 152/82 mmHg among 1238 participants in the Hemodialysisstudy 3 or in another study including 

414 Italian PD patients, in which the

prevalence of hypertension was 88%based on of ce BP$140/90 mmHg and69% based on BP load  .30%.12 Some

have theorized that better BP control inPD patients couldbe explained in part by removal of vasopressors and sodiumpump inhibitors by PD.13

In another study, the comparison of 22patientsonHDwith24patientsonPD

with 44-hour ambulatory BP monitor-ing showed no differences in daytimeand nighttime BP.14 Nonetheless, high-

quality head-to-head studies are sparseand the epidemiology of hypertensionmay be similar to that seen among HDpatients.15

Among PD patients, volume excess, asassessed by tracer dilution, was commonand was related to DBP and eccentric leftventricular hypertrophy (LVH).16 Volume

overload in PD patients may be related tothe peritoneal transport characteristics.17

High transporters tend to have a higherBP; ultraltration may restore their BPto more normotensive levels.17 In a smallstudy, patients on continuous cyclic PD

were reported to have a greater left ven-tricular mass compared with those oncontinuous ambulatory PD.18 This wasthought to be a result of greater volumeoverload.18

DIAGNOSIS

The diagnosis of hypertension among patients on HD is challenging and this

maylead to overtreatment or undertreat-ment of hypertension.19–22 Diagnosing hypertension is dif cult for several rea-sons.23 BP in these patients is often mea-

sured without attention to technique.24

BP declines during HD with ultraltra-

tion. This decline in BP can be variableand in part is related to the magnitudeand intensity of ultraltration.25 For ex-ample, those patients who have a large

volume removed over a short period of time may have a large decline in BP.These patients may also gain the removedvolume backover the interdialytic intervaland have a large increase in BP.26 Predial-

 ysis BP may therefore be hypertensiveand postdialysis BP may be hypotensive.

It therefore becomes unclear which BP

measurement to use to diagnose hyper-tension,27 and substantial errors can oc-cur both in detecting hypertension and

assessing its severity.28,29 Both predialysisand postdialysis BP measurements arehighly variable such that the variability between patients is about the same as var-iability in an individual patient overtime.30 In addition, HD patients have sig-

nicant seasonal variability in BP; BP ishighest during winters and lowest dur-ing summers.31 This may be related to

temperature-induced vasodilation. Al-though signicant relationships existbetween both predialysis and postdial-

 ysis BP and interdi alytic amb ulatory 

BP,32 a meta-analysis has shown thatpredialysis and postdialysis BP mea-surements agree poorly with interdia-lytic ambulatory BP.33 Accordingly,

among HD patients, large errors arepossible when using predialysis or

postdialysis BP to judge the magnitudeof elevation in interdialytic ambulatory BP.

The existing, although somewhat

dated, National Kidney Foundation Kid-ney Disease Outcomes Quality Initiativeguidelines recommend that BP measure-ments should be ,140/90 and ,130/80mmHg before and after HD, respec-tively.34 Use of predialysis or postdialysisBP measurements to make management

decisions in the interdialytic period canbe problematic. For example, in a sur-vey in the United Kingdom, centersthat achieved better postdialysis BP

targets had more intradialytic hypoten-sion.35 What is clear is that interdialyticweight gain increases predialysis BP3,36–39

and provokes the use of antihypertensive

therapy.36,37 However, interdialyticweight gain does not correlate with inter-

dialytic ambulatory BP.40,41 Therefore,whether achieving these peridialysis BPtargets would cause clinical harm (orbenet) remains unknown.

Usingall BP values measuredduring amid-week dialysis may serve as a moreuseful tool to estimate interdialytic am-bulatory BP.42 Although the mean in-tradialytic BP serves as a useful tool toassess hypertension, the calculation of median intradialytic BP is computation-

ally easier than calculating the mean. It

may therefore be used as a bedside toolto predict interdialytic ambulatory BP. A mid-week median intradialytic BP of 

$140/90 mmHg has sensitivity andspecicity that exceeds predialysis orpostdialysis measurements and can serveas a rapid and convenient tool to assesshypertension in long-term HD pa-tients.42 However, this is the method of 

last resort because better methods areavailable to evaluate hypertension inHD patients.

Home BP monitoring is a practical way to diagnose and manage hypertension inall patients with kidney disease.43,44 HomeBP monitoring is recommended by both

the American Heart Association and theEuropean Society of Hypertension for di-agnosing and managing hypertension.45,46

Home BP monitoring is especially valu-

able in diagnosing and managing hyper-tension for those on HD for the following 

reasons.47 Home BP correlates moreclosely with ambulatory BP comparedwith predialysis or postdialysis BP record-ings.48 Home BP can track changes in BP

evoked by the reduction in dry weight.49

Home BP, compared with predialysis orpostdialysis BP recordings, is much morereproducible from one week to the next.49

Home BP is superior to measurementsmade in the dialysis unit, even when thedialysis unit measurements are made us-

ing recommended techniques, in predict-ing the presence of target organ damage(echocardiographic LVH)50,51 or long-term outcomes such as cardiovascular

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events52 or mortality.52–55 The associationof BPand outcomes is discussed further inthe section on prognosis. A recent trialrandomized stable HD patients to home

BP-guided therapy or predialysis BP-guided therapy.56 The primary goal was

to assess change in interdialytic ambula-tory BP at 6 months and change in echo-cardiographic LVH. There was no changein ambulatory BP at 6 months in the pre-

dialysis BP-guided therapy group. A sig-nicant decrease in ambulatory SBP (butnot DBP) was noted at 6 months in thegroup treated using home BP recordings.Between-group differences were signi-cant. Given the small number of patientsand variability in timing of echocardio-

graphic left ventricular mass measure-

ments, no between-groups differenceswere noted. Another trial randomized 17HD patients to usual care and 17 patients

to home BP monitoring. Signicant im-provement in average weeklySBPwasseenin the home BP group only.57 These datasupport the use of home BP measurementto manage HD patients.

Among HD patients, the timing and

frequency of home BP monitoring is of particular importance.HomeBP increaseson average at a rate of 4 mmHg every 10

hours elapsed after dialysis.58

Therefore,measurement soon after dialysis or justbefore dialysis will underestimate or over-estimate the burden of hypertension.

Therefore, it is important to measure BPat various intervals after dialysis. Simply obtaining a BP measurement 20 minutespostdialysis may not yield the most repre-

sentative interdialytic BP.59 We recom-mend that measurements be made twice

daily (on waking up in the morning and just before going to sleep) after a midweek dialysis for 4 days,60 given that inter-dialytic BP measures may more capably 

predict LVH and mortality.50–55 Thesemeasurements allow an adequate numberof measurements fordiagnosing and man-aging hypertension. For long-term follow-up, monthly measurement (over 4 daysafter a midweek dialysis as noted above)should suf ce in most patients. More fre-

quent measurements may be needed in in-dividuals who are clinically unstable.

Ambulatory BP monitoring, among HD patients, is held to be the gold

standard for diagnosing hyperten-sion.27,61–63 Compared with peridialyticBP recordings, it correlates better withLVH50 and all-cause mortality.64 While

using a validated monitor,65 we re-commend measuring BP over the entire

interdialytic interval (44 hours). We rec-ommend recording BP every 20 minutesfrom 6 AM to 10  PM and every 30 minutesfrom 10   PM  to 6   AM66 As in the case of 

home BP, interdialytic SBP increases, al-beit at a slower rate of 2.5 mmHg every 10 hours.67,68 Because a much greaternumber of measurements during the in-terdialytic interval are typically availablecompared with home BP, patterns of BPcan be evaluated. Figure 1 illustrates the

pattern of BP and heart rate over an in-

terdialytic interval. Among HD patients,ambulatory BP monitoring remains a re-search technique.

In approximately 10%–15% of pa-tients, instead of decreasing, BP paradox-ically increases during dialysis.69 Thesepatients have intradialytic hypertension.Intradialytic hypertension is dened indifferent ways. These denitions include

the following: (1) a discrete change in BPfrom predialysisto postdialysisin a certainnumber of dialysis treatments; ( 2) regres-

sion of all intradialytic BP with a slope.

0;and (3) a change of .0 mmHg from pre-dialysis to postdialysis. Intradialytic hy-pertension is associated with greater

short-term (6-month) mortality in HDpatients.70 In another cohort, an increasein SBP by  .10 mmHg during HD oc-curred in approximately 10% of incident

patients. Although this increase in SBPduring HD was associated with decreased

2-year survival, these   ndings were lim-ited to patients with predialysis SBP of 

,120 mmHg.71 Although the exactmechanism of this relationship is un-

clear,72,73 a study shows that intradialytichypertension in HD patients using deni-tion 2 noted above is associated with bothvolume excess and interdialytic hyper-tension.74 Another study, using denition1, conrmed the association between in-tradialytic hypertension and interdialytic

hypertension.75

At least two studies suggest that low-ering dry weight may improve inter-dialytic hypertension. Cirit et al. treated

seven hypertensive patients on HD withmarked cardiac dilation that experiencedparadoxical hypertension during dialy-sis.76 After probing dry weight, both BP

and postdialysis weight was reduced; theBP reduction was 46/22 mmHg and post-

dialysis weight was reduced by 6.7 kg. Theauthors concluded that BP may paradoxi-cally rise with ultraltration when patientsare volume overloaded. Dry weight was re-duced progressively in the randomized

Dry-Weight Reduction in HypertensiveHemodialysis Patients (DRIP) trial, as dis-cussed below.77 Those patients with intra-dialytic hypertension who had additionalultraltration and therefore a reduction indry weight had improvement in both intra-

dialytic and interdialytic hypertension.74

This suggests that an appropriate therapy for this conditionwould be to further lowerdry weight. However, the phenomenon of 

intradialytic hypertension is complex andincompletely understood; pilot studies sug-gest that endothelial dysfunction may beoperative in its pathogenesis.78

Home BP measurement is a practicalway to measure and manage hypertension

amongHDpatients.Thetargetsoftherapy using home BP monitoring will need to bedened in future trials. Guidelines of the

American Heart Association de

ne hy-pertension as home BP of at least 135/85mmHg 45; lowering BP in the interdialyticperiod to at least 140/90 mmHg appears

to be a reasonable goal (Table 1).

NONPHARMACOLOGICTREATMENT

Once an accurate diagnosis is made, thetherapy of hypertension among HDpatients rests on nonpharmacologicmanagement. Although scarcely studied,

one small study lasting 6 monthsshowed a benecial effect of exercise onBP and medication requirements.79 Ex-ercise consisted of using a stationary bi-cycle during dialysis.79 Besides thispromising strategy, the nonpharmaco-logic management of hypertension is

based on four principles: dietary sodiumrestriction, individualizing dialysate so-dium, the management of dry weight,and providing an adequate duration of 

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dialysis. These principles are further dis-cussed.

Dietary Sodium RestrictionDietary sodium restriction limits inter-dialytic weight gain and improves the

feasibility of achieving dry weight.80,81

Instead of restricting dietary sodium, pa-tients on HD are sometimes prescribeduid-restricted diets. With the exception

of treating hyponatremia, there is no scien-tic basis for prescribing a  uid-restricteddiet in these patients.82

Recent guidelines suggest that elderly persons and individuals with CKD aremost likely to derive the greatest benetsfrom dietary sodium restriction.83 These

guidelines are even stricter on sodium in-

take than those advocated earlier (2 g/d).Dietary sodium restriction to no morethan 1.5 g sodium (or approximately 

65 mmol) per day is now recommended.Although no randomized trials have

been performed among patients withESRD, observational studies among long-term HD patients suggest that re-stricting dietary sodium and achieving dry 

weight can improve LVH.84

Individualizing Dialysate Sodium

High sodium dialysis was initially pre-scribed to provide hemodynamic stability,fewer disequilibriumsymptoms,and fewermuscle cramps.85 Early studies found that

high sodium dialysate among normoten-sive patients reduced dialysis-induced hy-potension and was not associated withlong-term hypertension.86 However, its ef-

fect among those with hypertension wasless clear.86 A double-blind crossover trial

in seven dialysis patients found that com-pared with dialysatesodiumof 135mEq/L,both dialysate sodium of 143 mEq/L orsodium gradient dialysate of 160–133

mEq/L were associated with greater inter-dialytic weight gain (2.2, 2.6, and 2.8 kg respectively).87 Another study showedthat interdialytic weight gain and thirstcan be provoked with the prescription of hypertonic dialysate.88 These  ndings arenow being recognized as important treat-

ment targets.89 The prescription of highsodium dialysate allows increased   uidvolume removal and better hemodynamicstability. However, it provokes increased

Figure 1.  Modeled trended cosinor BP and pulse rate in HD patients. Notice the linear trend in SBP, DBP, and pulse pressure but the lack thereof in heart rate. Reprinted fromreference 67, with permission.

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respectively. An elaborate protocol wasavailable to guide   uid managementbased on RPV-guided monitoring; al-gorithm use was encouraged but not

mandated. Furthermore, highly variableimplementation of the monitoring and

interventional algorithm occurredwithin and across dialysis units. At base-line, as determined by RPV slope pat-terns, patients in the conventional groupappeared to be more volume overloaded

compared with the RPV-guided group.At 6 months, both groups had similarRPV slopes. Thus, the conventionalgroup appeared to have had greater vol-ume challenge than the interventiongroup. Although this was a randomized

trial, the  ndings should be interpreted

with caution for the above reasons.To study theeffect ofvolume statuson

mortality, Wizemann et al. followed 269

prevalent HD patients for several years.108 They measured hydration stateusing a body composition analyzer. If there was  .15% excess of extracellularwater (2.5 L volume excess), they classi-ed such patients as volume overloaded;

25% of the patients had excess extracel-lular uid (ECF) volume. In a multivar-iate adjusted analysis, they found that

excess volume was associated with highmortality. Compared with those withoutexcess ECF volume, the hazard ratio of mortality with excess   uid volume was

2.1 (95% CI, 1.39 to 3.18; P =0.003). Al-though the study did not examine theeffect of reduction in ECF volume onsubsequent outcomes, such studies

need to be performed in the future.Inrig   et al.  compared the change in

pulse pressure during dialysis as a risk factor for hospitalization and mortality among prevalent HD patients participat-ing in a randomized controlled trial.109

They found that patients who had theleast change in pulse pressure from be-fore to after dialysis had clinical charac-teristics indicating volume overload.Among these patients, lowering of thepulse pressure from before to after dial-

 ysis was associated with lower hospitali-

zation and mortality outcomes. Becausepulse pressure is largely driven by SBP, itis likely that lowering of pulse pressurewith dialysis reects more volume loss

and a lower ECF volume state, and may provide better cardiovascular outcomes,perhaps through less pressure/volumestress on the heart.

Potential Hazards of Probing Dry Weight 

There are potential hazards related toprobing dry weight, none of which havebeen adequately examined.77 These in-clude the following: (1) increased risk 

of clotted angioaccess, ( 2) increasedrate of attrition in residual renal func-tion, and (3) complications related tointradialytic hypotension. Intradialytichypotension, besides requiring morenursing interventions, can be complicatedby cerebral hypoperfusion, seizures, myo-

cardialdysfunction, and mesenteric ische-

mia. Furthermore, it has been associatedwith mortality.110 The relative risks andbenets of probing dry weight need to

be examined in long-term randomizedtrials.

Providing Adequate Duration of DialysisThe European Best Practice Guidelines

recommend that dialysis should be de-livered at least three times a week and thetotal duration should be at least 12 hours

per week, unless substantial residual re-nal function is present.111 An increase intreatment time and or frequency shouldbe considered in patients who experi-

ence hemodynamic instability or remainhypertensive despite maximal possibleuid removal.

In the United States, a recent study 

reported that the average duration of dialysis among 32,065 participants in the

ESRD Clinical Performance MeasuresProject was 217 minutes.112 The inter-quartile range was 195–240 minutes.This means that one-quarter of the pa-

tients were receiving  ,3 hours and 15minutes of dialysis and only one-quarterof the patients were receiving .4 hoursof dialysis.

Although what constitutes an ade-quate dialysis is still debated, it is clearthat patientswho shorten treatment have

hypertension that is more dif cult tocontrol.5 Patients who dialyze 8 hoursthree times a week have excellent BPcontrol, minimal requirement for

antihypertensive drugs, and excellentlong-term survival.41,113 In a random-ized crossover trial of 38 patients, theeffects of 4-hour dialysis to 5-hour dial-

 ysis were evaluated.114 Hemodynamicstability and hypotensive episodes were

fewer with longer dialysis, especially among older patients (aged .65 years).However, these data are dif cult to gen-eralize because treatment was evaluated

only over 2 weeks and those requiring .4 L ultraltration were excluded. Lon-ger or more frequent dialysis sessions, ingeneral, are associated with less hemo-dynamic instability, better achievementof postdialysis dry weight, better controlof BP, and the reduced need for antihy-

pertensive drugs.

FREQUENT DIALYSIS AND ITSEFFECT ON BP

Observational studies suggest that con-version of patients from three times aweek conventional dialysis to nocturnaldialysis may improve BP and left ven-

tricular mass.115 In a cumulative analysisof 72 patients from nine centers it wasnoted that predialysis SBP and DBP fell

within 1 month of dialysis by 13/7mmHg from 163/94 mmHg.116 This re-duction was accompanied by a 1% de-cline in postdialysis weight. Although BP

did not change after 1 month, the num-ber of antihypertensive agents declinedsignicantly. At baseline, 54% of patientswere not taking antihypertensive drugs,

whereas at 12 months after switching todaily dialysis, 75% were not taking anti-

hypertensive agents.Several observations have suggested

improvements in BP and left ventricularmass among patients undergoing more

frequent dialysis. For example, Chanet al . reported an improvement in bothSBP and DBP, a reduction in antihyper-tensive drugs and doses, and a reductionin left ventricular mass in patients un-dergoing nocturnal dialysis.115 Thisgroup also reported an improvement in

pharyngeal size among nocturnally dia-lyzed patients.117 This may improvesleep apnea and consequently ambula-tory BP. Another mechanism of BP

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reduction with frequent dialysis is sug-gested to be an increase in arterial com-pliance and consequently improvementin baroreex sensitivity.118 Other mech-

anisms may be better volume and toxinremoval.119

A randomized controlled trial as-signed 52 HD patients to either frequentdialysis, six nights per week, or conven-tional three times a week treatment. In

the frequent dialysis group, the resultsshowed an improvement in cardiac mag-netic resonance–imaged left ventricularmass and a reduction in the need for an-tihypertensive medications.120 The Fre-quent Hemodialysis Network (FHN)study randomized HD patients to either

conventional dialysis three times weekly 

or more frequent in-center dialysis; theprimary endpoint was an improvementin joint composite end points of either

(1) death orLVHor ( 2) death or physicalhealth composite. The primary endpoint was met, but perhaps the most no-table   ndings were an improvement inSBP, a reduction in antihypertensivedrug use, and an improvement in leftventricular mass.121 These ndings sug-gest better achievement of dry weight inthese patients.122 Improvement in SBP

was also noted in the companion FHNNocturnal trial.123 Increasing the treat-ment duration may improve hemody-namic stability of dialysis and make the

procedure more tolerable, but it is not arequirement for improvement in leftventricular mass. Shortening the pro-cedure to tailor dialysis to a minimum

Kt/Vmay provoke intradialytic symptoms,postdialysis fatigue, and nonadherence

to therapy; thus, this is not recommen-ded.124 Normotension can be achievedindependently of the duration of dialysisif the control of volume is adequate.125 In

fact, left ventricular mass index was alsoimproved to a comparable degree inDRIP trial participants, in which the du-ration of dialysis was not altered but thedry weight was challenged.126

PHARMACOLOGIC TREATMENT

All classes of antihypertensive drugs,except diuretics, are useful for managing 

hypertension in HD patients.127 Diuret-ics are generally ineffective at very low GFR. There is no role of loop diureticseven when given in a high dose (e.g., as

high as 250 mg intravenously of furose-mide) among anuric HD patients.128

Tissue Doppler imaging revealed thatcentral cardiac hemodynamics were un-altered when anuric HD patients weregiven even such high doses of loop di-

uretics. Given the ototoxicity associatedwith high doses of loop diuretics, theiruse, especially in high doses, is not rec-ommended. Further research is neededto clarify the role of loop diureticsamong patients with substantial residualrenal function (e.g., patients new to

long-term dialysis). Consideration of 

pharmacokinetics is important whenprescribing these drugs.129 In general, if patients are volume overloaded, antihy-

pertensive medications are less effective.Paradoxically, among HD patients, agreater use of antihypertensive medica-tions is associated with a higher BP.130

However, causality must not be as-sumed. It is more likely that excessive

antihypertensive medication may inter-fere with achievement of dry weight.

Drugs that block the renin-angiotensin

system are often recommended as 

rst-line therapy for HD patients because of their tolerability and extrapolated cardio-vascularbenets in the general population

with heart and kidney disease. Only oneprospective trialcomparedan angiotensin-converting enzyme inhibitor (fosinopril)versus placeboin HD patients, allof which

had LVH. Although hypertension wasnot an inclusion criterion, all patients

underwent a single-blind run-in periodwith 5 mg of fosinopril, and those whoexperienced symptomatic hypotensionorhadaSBP ,95 mmHg4–6 hours aftertest dose were excluded. Subsequently, in

the Fosinopril and Dialysis Trial, 400 HDpatients received 20 mg of fosinopril ver-sus placeboin an equal ratio. After4 yearsof follow-up, there were no differencesbetween the two treatment groups inthe primary end point of cardiovascular

events that included cardiovasculardeath.131 Another smaller trial comparedcandesartan versus placebo in HD pa-tients, but noted a nearly 3-fold reduction

in cardiovascular events with active treat-ment versus placebo.132 These conicting results indicate the need for larger studies.There are no studies in PD patients, nor

are there any studies in HD patients withdiabetes.

 b-Blockers may be an effective thera-peutic strategy in HD patients with re-duced ejection fraction (,35%). Onestudy randomized 114 (not necessarily hypertensive) patients with dilated car-

diomyopathy to 25 mg of carvedilol twicedaily or placebo for 2 years.  b-Blockertreatment reduced hospitalizations (RR,0.44) and all-cause death (RR, 0.51).133

Regrettably, the reduction in all-causemortalitywith antihypertensive drug ther-

apy in HD patients has not been realized

with adequately powered randomizedcontrolled trials. This may be due to mul-tiple reasons, including the low numbers

of patients. Nonetheless, meta-analysesof these trials show improvement in thecardiovascular event rate.134,135 Thesebenets are especially seen among individ-uals who have hypertension.135

The recently reported Hypertension in

HemoDialysis Patients Treated with Ate-nolol or Lisinopril (HDPAL) trial ran-domly assigned 200 patients to either

open-label lisinopril (n=100) or atenolol(n=100) each administered three timesper week after dialysis. The HDPAL trialaimed to determine whether angiotensin-

converting enzyme inhibitor–based an-tihypertensive therapy causes a greaterregression of LVH compared with b-blocker–based antihypertensive ther-

apy among maintenance HD patientswith echocardiographic LVH and hyper-

tension.136 Monthly monitored home BPwas controlled to  ,140/90 mmHg withmedications, dry weight adjustment, andsodium restriction. The primary outcome

was the change in the left ventricular massindex from baseline to 12 months. Atbaseline, 44-hour ambulatory BP wassimilar in the atenolol (151.5/87.1mmHg) and lisinopril groups, and im-proved similarly over time in both groups.However, monthly measured home BP

was consistently higher in the lisinoprilgroup despite needing a greater numberof antihypertensive agents and a greaterreduction in dry weight. An independent

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data safety monitoring board recommen-dedearlytermination of thetrial because of cardiovascular safety. Serious cardiovascu-larevents occurred in 16 participants in the

atenolol groupwho had20 events and in 28participants in the lisinopril group who

had 43 events (incidence rate ratio [IRR],2.36; 95%condence interval, 1.36 to 4.23;P =0.001). Combined serious adverseevents of myocardial infarction, stroke,hospitalization for heart failure, or cardio-

vascular death occurred in 10 participantsin the atenolol group who had 11 eventsand in 17 participants in the lisinoprilgroup who had 23 events (IRR, 2.29;95% CI, 1.07 to 5.21;  P =0.02). Hospital-izations for heart failure were worse in the

lisinopril group (IRR 3.13; 95% CI, 1.08 to

10.99;  P =0.02). All-cause hospitalizationswere higher in the lisinopril group (IRR,1.61; 95%condence interval, 1.18 to 2.19;

P =0.002). The left ventricular mass index improved with time; no difference be-tween drugs was noted. These data appearto suggest that among maintenance dial-

 ysis patients with hypertension and LVH,atenolol-based antihypertensive therapy may be superior to lisinopril-based ther-

apy in preventing cardiovascular morbid-ity and all-cause hospitalizations. Larger

multicenter trials should be performedto conrm these provocative data from asingle center.

NONVOLUME-DEPENDENTCAUSES OF HYPERTENSION INDIALYSIS PATIENTS

An increase in BP is a well recognized

complication of erythropoietin therapy inHD patients.137 Hypertension is commonwith erythropoietin therapy, with approx-imately 30% of patients either developing 

hypertension or requiring an adjustmentin antihypertensive medications.138,139

The etiologyof hypertensionwith erythro-poietin therapy is not clear. The incidenceof erythropoietin-induced hypertensioncorrelates with the erythropoietin dosebut appears to be independent of its ef-

fect on red blood cell mass and viscos-ity.140,141 Available data suggest that themost likely mechanisms involve either anincrease in production or an enhanced

response to the effect of various vasoac-tive substances.142,143 Several studieshave found that erythropoietin-inducedhypertension in hemodialyzed patients is

associated with either a signicantly in-creased circulatingendothelin-1concentra-

tion or enhanced vasoconstrictive responseto endothelin-1.144–146 Erythropoietintreatment has also been shown to be as-sociated with an accentuated increase in

the BP response to angiotensin II infusioncompared with the BP response beforeerythropoietin therapy.147 This apparentincreased sensitivity to angiotensin II cor-related with the erythropoietin-inducedincrease in BP. Studies have also shownnoradrenergic hypersensitivity in hemo-

dialyzed patients with erythropoietin-

induced hypertension.148

The effect of erythropoietin on BP canbemissedbecauseofvariabilityinBPfrom

predialysis to postdialysis and the lack of home or ambulatory BP measurements.Studies that failed to detect increases in BPwith erythropoietin therapy may havemanaged hypertension more aggressively through the prescription of antihyperten-

sivedrugsorcloserattentiontodryweight.Erythropoietin therapy was an indepen-dent predictor of hypertension diagnosed

by ambulatory BP monitoring.8

Somestudies show an association of erythropoi-etin use with nondipping.149 Increase inBP with erythropoietin occurs more com-

monly in individuals with preexisting hy-pertension150,151 or a family history of hypertension.152

Prevention of erythropoietin-induced

hypertension, and other complications,is a clinical challenge with several possible

management strategies. Recommendedstrategies, with little good evidence tosupportthesepractices, have included thefollowing: changing the route of admin-

istration (subcutaneous versus intrave-nous), reducing the goal hemoglobin level(especially in patients who are unrespon-sive to erythropoietin therapy), starting with a low erythropoietin dose and in-creasing the dose slowly, and avoiding theuse of erythropoietin altogether.

Sleep apnea is very common in dialysispatients and is often associated with vol-ume overload. Hypopneic spells during the night leadto nocturnal hypoxemia and

provoke intense sympathetic arousal andan increase in nocturnal BP.153 Table 2summarizes thekey points in themanage-ment of hypertension.

Hypoxemia that characterizes sleepapnea in patients with ESRD may cause

hypertension.154 Patients with ESRDwith sleep apnea have shown a 7-foldhigher prevalence of resistant hyperten-sionthanindividuals in the general hyper-

tension population.155 In the recumbentposition, the volume overload is redis-tributed from the legs to the chest andneck areas and may induce a periphar-

 yngeal and upper airway resistance.156

Volume overload and the specic redis-tribution described in patients with

ESRD may be not only a consequence

but also an important cause of obstruc-tive sleep apnea.157

RELATIONSHIP OF BP ANDMORTALITY 

AmongHD patients,the relationship of BPwithcardiovascularoutcomesisasubjectof 

much controversy.158–164 As previously discussed, controversy relates to the spe-cic relationship between the BP measure-

ment times and technique (predialytic,postdialytic, or intradialytic BP measure-ments or interdialytic ambulatory BP) andmorbidity and mortality. Some studies

suggest an association of high BP withstrokes,165,166 cerebralatrophy,167cardiovas-cular events,168 complex cardiac arrhyth-mias,169 the development of congestive

heart failure,161 and all-cause mortal-ity.170 Other studies suggest that low BP

measured either predialysis or postdialy-sis is associated with increased mortal-ity.164,171–173 This association of low BPand mortality is further magnied when

BP is considered as a time-dependent co-variate.173 High BP measured either be-fore dialysis or after dialysis are either notassociated or minimally associated withincreased mortality. The phenomenon of lower BP being associated with increasedmortality has been labeled as reverse ep-

idemiology of hypertension. This hasraised concerns regarding lowering of BP among hypertensive HD patients.174,175

Other studies have demonstrated a direct

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relationship between BP and mortal-ity.170,176 Consideration of the patient

characteristics, dialysis practices, andBP measurement techniques is usefulwhen evaluating these outcomes.

Consideration of the level of illness and

thevintageofthepatientarealso instructiveto ascertain the value of hypertension as arisk factor among HD patients. Examining the outcomes of 2770 patients on PD

provides such insights.15 These patientswere studied between 1997 and 2004 and

had been on PD for at least 180 days inEngland and Wales. In a fully adjustedanalysis, greater SBP, DBP, mean arterial,and pulse pressure were associated with de-

creased mortality among patients who hadbeen on dialysis for  ,1 year. However,greater SBP and pulse pressure (but notmean arterial pressure and DBP) were as-sociated with increased mortality among patients who had been on PDfor$6 years.In a subgroup of patients who were placed

on the transplant waitlist within 6 monthsof starting RRT and were presumably healthier, greater SBP, DBP, mean arterialor pulse pressure were not associated with

decreased mortality in the  rst year. Simi-larly, among 16,959 dialysis patients in theUnited States, low SBP(,120 mmHg) wasassociated with increased mortality in years

1 and 2.177 However, high SBP ($150mmHg) was associated with increased

mortality among patients who survived atleast 3 years.177

Regional differences in mortality areunlikely to be caused by patient-specic

characteristicsalone.Forexample,acenterin Tassin, France, reported a mortality rateof 45 per 1000 patient-years.176 By con-trast, Degoulet  et al., also from France,reported a mortality rate of 96 per 1000patient-years.178 Differences in outcomesmay be the result of center-specic prac-

tices. Patients reported by Charra et al. in

Tassin, France, are dialyzed long hourswith low sodium dialysate and are givenlow-sodium bread from the dialysis

unit.176The vast majority of these patientsbecome normotensive without needing antihypertensive drugs.

BP measurement technique is alsoquite likely to contribute to variation inthe relationship between BP and out-

comes. For example, Amar  et al.   werethe rst to discover the strong relationshipbetween ambulatory BP and mortality.53

These authors reported that nocturnalSBP was directly related to mortality.Agarwal  et al.  have used ambulatory BPto detect its relationship with mortality.

In a cohort of approximately 150 patients,the authors found a direct and statistically signicant relationship of both home andambulatory BP with mortality.54 No such

relationship was detectable using predial- ysis and postdialysis BP recordings. In a

larger cohort followed for a longer time,the authors found a W-shaped relation-ship between both ambulatory BP andhome BP and all-cause mortality 64 At ex-

tremes of BP, mortality was noted to behigh. Compared with ambulatory BP, theoptimal BP ranges for home BP were ap-proximately 10 mmHg higher.

HYPERTENSION IN PEDIATRICDIALYSIS PATIENTS

Young adults with childhood-onset ESRDhave signicantly elevated cardiovascular

risk compared with the general popula-tion. Data from the Late Effects of RenalInsuf ciency in Children cohort study of 249 Dutch adult patients with onset of 

ESRD between 0 and 14 years of agedemonstrated that the overall mortality 

risk ofthe patients with ESRD was 31timesthat of age-matched Dutch citizens.179

Cardiovascular disease accounted for41% of all mortalities, with cardiac death

becoming the most common cause of mortality after 10 years of receiving RRT.179 Similarly, among 1380 patientswith childhood-onset ESRD who died be-fore aged 30 years, 23% of deaths werecardiovascular in origin; the cardiovascu-lar death rate was 1000 times higher

among children with ESRD than in the

general population, and was 100 timeshigher among young adults with ESRDthan in the general population.180 Al-

though the number of patients withchildhood-onset ESRD is small comparedwith the overall adult ESRD population,they constitute a unique group in whomcontrol of cardiovascular riskfactors is key to ensuring long-term survival.

As in adult ESRD patients, hyperten-sion is the most common modiablecardiovascular risk factor in children on

dialysis. Mitsnefes et al.181

reported thatapproximately 60% of pediatric dialysispatients had uncontrolled hypertension,dened as measured BP$95th percen-

tile. Young age, recent dialysis initiation,and HD modality were identied as risk factors for having uncontrolled BP. Sim-ilar poor control of hypertension using 

predialysis and postdialysis BP measure-ments in American dialysis patients has

been reported by Chavers et al.6 for HDpatients and Halbach  et al.182 for bothHD and PD patients. In the latter study,demographic factors such as young age

and black race and treatment factorssuch as prescription of antihypertensivemedications were also identied as risk factors for poorly controlled hyperten-sion. More recent data from the Euro-pean Registry for Children on RenalReplacement Therapy on BP control

among pediatric ESRD patients inEurope, including patients receiving HD, PD, and postrenal transplant, con-rmed the high rate of hypertension in

Table 2.   Management of hypertension

Summary Statements

1. Volume overload is often an overlooked

factor in managing hypertension.

Erythropoietin-induced hypertension and

untreated sleep apnea are other important

causes.2. Volume overload is associated with

increased mortality in HD patients.

3. The iterative trial-and-error method of dry

weight assessment remains the current

clinical standard in assessing volume status.

4. Dietary salt restriction and individualizing

dialysate sodium prescription may improve

the feasibility of achieving dry weight.

5. Probing dry weight can improve BP among

hypertensive HD patients. The long-term

risks and benets of probing dry weight

need to be examined in future trials.

6. Delivery of dialysis of at least 4 hoursduration three times a week may facilitate

volume and hypertension control.

7. Antihypertensive drugs are frequently

needed to control hypertension but are an

adjunct to facilitate volume control.

Diuretics have little to no role in patients

with ESRD. b-blockers may be preferred to

other agents.

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pediatric ESRD. Hypertension was pres-ent in 69.4% of HD patients (using BPrecordings in the peridialytic period),68.6% of PD patients, and 66.9% of 

transplant recipients.183 Among dialysispatients, younger age, recent dialysis ini-

tiation, and HD modality were the mostimportant risk factors for hyperten-sion.183 Of note, all of these studies arenotable for their reliance upon registry 

data; thus, there is limited informationavailable on the technique and/or fre-quency of BP measurement, or the goalsof hypertension management.

LVH is the best-studied complicationof hypertension in pediatric dialysis pa-tients. A study by Mitsnefes  et al.  dem-

onstrated increased left ventricular mass

at the start of dialysis, and also showedthat this increase persisted over a meanfollow-up of 10 months.184 Risk factors

for LVH included anemia, longer du-ration of renal disease before start of dialysis, and higher SBP. In a recent mul-ticenter study from the InternationalPediatric Peritoneal Dialysis Network,LVH was present in 48% of hypertensive

PD patients, with   uid overload, highbody mass index, and hyperparathyroid-ism being the primary determinants of 

LVH.185

Studies comparing the fre-quency of LVH in children on PD orHD have had variable results. An Amer-ican study showed that children on HD

had LVH more often (85%) than chil-dren on PD (68%).186 Similarly, a Finnishstudy found that 45% of children on PDhad LVH; LVH in this study was highly 

correlated with the severity of hyperten-sion (pressure overload) and with hyper-

volemia as reected by the plasma atrialnatriuretic peptide level.187 On the con-trary, the results from a German study showed similar left ventricular mass index 

with both modes of treatment.188 It istherefore likely that the prevalence of leftventricular in pediatric dialysis patients ismore dependent on the overall control of BP and on volume status than on dialysismodality.

Diagnosisofhypertensionandachieve-

ment of BP control pose some uniquechallenges in pediatric dialysis patients.With respectto diagnosis, age-appropriatenormative values as published by the

National High Blood Pressure EducationProgram(NHBPEP)mustbeused,andBPcuffs appropriatefor the child’supperarmmust be selected.189 Normal BP in chil-

dren is dened as a BP value below the90th percentile for age, sex, and height,

and hypertension is dened as BP valuesrepeatedly at or above the 95th percen-tile.190 Thus, the clinician must consulttables of normative BP values in order to

correctly categorize a child’s BP as normalor elevated. It should also be noted thatthere are no existing consensus recom-mendations that specically address theoptimal BP treatment goal for childrenon dialysis. Both the NHBPEP and theKidney Disease Outcomes Quality Initia-

tive have recommended that hypertensive

children with CKD should be treated to aBP below the 90th percentile,189,190 butpediatric dialysis patients were not specif-

ically mentioned in either of these reports.Given that normalization of BP has beenshown to lead to regression of LVH in atleast one study of pediatric HD pa-tients,191 recommendations to achieve aBP value below the 90th percentile would

seem appropriate until further evidencecan be generated. Among pediatric pa-tients on dialysis, further studies are

needed to de

ne the accuracy of peridia-lytic BP monitoring in determining inter-dialytic ambulatory BP.

Strategies to control hypertension in

pediatric dialysis patients are similar tothose used in adults, and include dietary sodium restriction and control of volumestatus.Vasodilatingantihypertensivemed-

ications are generally avoided so as not tocompromise uid removal. A unique and

vexing issue in the treatment of hyperten-sive pediatric dialysis patients is how toaccurately assess and achieve dry weight.Infants and young children in particularare expected to demonstrate progressive

weight gain and linear growth, a processthat does not proceed in a predictablelinear manner.192 Thus, it is unreasonableto expect that pediatric patients canachieve and maintain a stable dry weight.Two potential approaches to this problem

have been studied: bioimpedance analysisand blood volume monitoring. In a recentsingle-center study, use of bioimpedanceanalysis to determine dry weight in a small

group of pediatric HD patients was asso-ciated with fewer episodes of pulmonary edema and decreased prevalence of LVHcompared with a group of historical con-

trols.193 A blood volume monitoring pro-tocol in a multicenter study demonstrated

improved control of hypertension withdecreased need for antihypertensive med-ications, although no signicant change inpostdialysis weight was seen.106 In pediat-

ric PD patients, a plasma atrial natriureticpeptide level .3.0 nmol/L was felt to re-ect hypervolemia on one study,187 butthis   nding has not yet been replicated.Clearly, further renement of how to es-tablish dry weight in pediatric dialysis pa-tients is required.

Hypertension is an important clinical

probleminHDpatients.Oftenmedication-directed approaches are utilized due toits perceived simplicity, as in the general

population. However, nonpharmacologicand dialytic approaches are more likely tobe successful and may target one of themajor factors that contribute to the de-velopment of congestive heart failure:central pressure/volume overload. Use of antihypertensive drugs may improve car-

diovascular outcomes;  b-blockers may be a preferred drug class. More clinical

trials are needed to evaluate optimal indi-vidualized strategies for dening targetsfor BP and controlling BP using pharma-cologic and nonpharmacologic strategies

in HD patients.

 ACKNOWLEDGMENTS

Reviewof anearlier versionof thisworkby the

publication committee of the American So-

ciety of Hypertension and the Hypertension

Advisory Group of the American Society of 

Nephrology is gratefully acknowledged. We

thank Tia A. Paul, University of Maryland

School of Medicine, Baltimore, for expert

secretarial support.

This work was supported, in part, by a

grant from the National Institutes of Health

(2R01-DK6203010) to R.A.

DISCLOSURES

None.

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REFERENCES

1. Agarwal R, Nissenson AR, Batlle D, Coyne

DW, Trout JR, Warnock DG: Prevalence,

treatment, and control of hypertension in

chronic hemodialysis patients in the United

States. Am J Med  115: 291–297, 2003

2. Salem MM: Hypertension in the hemodial-ysis population: A survey of 649 patients.

Am J Kidney Dis  26: 461–468, 19953. Rocco MV, Yan G, Heyka RJ, Benz R,

Cheung AK; HEMO Study Group: Risk fac-

tors for hypertension in chronic hemodialy-

sis patients: Baseline data from the HEMO

study. Am J Nephrol  21: 280–288, 2001

4. Raine AE, Margreiter R, Brunner FP, Ehrich

JH,Geerlings W, Landais P, LoiratC, Mallick

NP, Selwood NH, Tufveson G: Report on

managementof renal failurein Europe, XXII,

1991.  Nephrol Dial Transplant  7[Suppl 2]:

7–35, 1992

5. Rahman M, Fu P, Sehgal AR, Smith MC: In-terdialytic weight gain, compliance with di-

alysis regimen, and age are independent

predictors of blood pressure in hemodialy-

sis patients. Am J Kidney Dis  35: 257–265,

20006. ChaversBM, Solid CA,Daniels FX,Chen SC,

Collins AJ, Frankeneld DL, Herzog CA:

Hypertension in pediatric long-term hemo-

dialysis patients in the United States. Clin J 

Am Soc Nephrol  4: 1363–1369, 2009

7. Grekas D, Bamichas G, Bacharaki D,

Goutzaridis N, Kasimatis E, Tourkantonis A:

Hypertension in chronic hemodialysis pa-

tients: Current view on pathophysiology

and treatment. Clin Nephrol  53: 164–168,2000

8. Agarwal R: Epidemiology of interdialytic

ambulatory hypertension and the role of 

volume excess. Am J Nephrol  34: 381–390,

20119. Boudville NC, Cordy P, Millman K, Fairbairn

L, Sharma A, Lindsay R, Blake PG: Blood

pressure, volume, and sodium control in an

automated peritoneal dialysis population.

Perit Dial Int  27: 537–543, 200710. Velasquez MT, Lew SQ, von Albertini B,

Mishkin GJ, Bosch JP: Control of hyper-

tension is better during hemodialysis than

during continuous ambulatory peritonealdialysis in ESRD patients. Clin Nephrol  48:

341–345, 199711. Rocco MV,Flanigan MJ,BeaverS, Frederick

P, Gentile DE, McClellan WM, Polder J,

Prowant BF, Taylor L, Helgerson SD; Report

fromthe 1995Core Indicators forPeritoneal

Dialysis Study Group: Report from the 1995

CoreIndicatorsfor Peritoneal DialysisStudy

Group. Am J Kidney Dis  30: 165–173, 1997

12. Cocchi R, Degli Esposti E, Fabbri A,

Lucatello A, Sturani A, Quarello F, Boero R,

Bruno M, Dadone C, Favazza A, Scanziani R,

Tommasi A, Giangrande A: Prevalence of 

hypertension in patients on peritoneal

dialysis: Results of an Italian multicentre

study.  Nephrol Dial Transplant  14: 1536–

1540, 199913. Weiler EWJ, Saldanha LF, Khalil-Manesh F,

Prins BA,PurdyRE, Gonick HC:Relationship

of Na-K-ATPase inhibitors to blood-pressureregulation in continuous ambulatory perito-

neal dialysis and hemodialysis.   J Am Soc Nephrol  7: 454–463, 1996

14. Tonbul Z, Altintepe L, Sözlü C, Yeksan M,

 Yildiz A, Türk S: Ambulatory blood pressure

monitoring in haemodialysis and continu-ous ambulatory peritoneal dialysis (CAPD)

patients.   J Hum Hypertens   16: 585–589,

2002

15. Udayaraj UP, Steenkamp R, Caskey FJ,

Rogers C, Nitsch D, Ansell D, Tomson CR:

Blood pressure and mortality risk on peri-toneal dialysis. Am J Kidney Dis  53: 70–78,

2009

16. Konings CJ, Kooman JP, Schonck M,

Dammers R, Cheriex E, Palmans Meulemans

AP, Hoeks AP, van Kreel B, Gladziwa U,van der Sande FM, Leunissen KM: Fluid

status, blood pressure, and cardiovascu-

lar abnormalities in patients on perito-

neal dialysis.  Perit Dial Int   22: 477–487,

2002

17. Tonbul Z, Altintepe L, Sözlü C, Yeksan M, Yildiz A, Türk S: The association of perito-

neal transport properties with 24-hour 

blood pressure levels in CAPD patients.Perit Dial Int  23: 46–52, 2003

18. Wang MC, Tseng CC, Tsai WC, Huang JJ:

Blood pressure and left ventricular hyper-

trophy in patients on different peritoneal

dialysis regimens.  Perit Dial Int  21: 36–42,

2001

19. Cannella G, Paolett i E, Ravera G,

Cassottana P, Araghi P, Mulas D, Peloso G,Delno R, Messa P: Inadequate diagnosis

and therapy of arterial hypertension as

causes of left ventricular hypertrophy in

uremic dialysispatients. Kidney Int 58: 260–268, 2000

20. Cheigh JS, Milite C, Sullivan JF, Rubin AL,

Stenzel KH: Hypertension is not adequately

controlled in hemodialysis patients.   Am J 

Kidney Dis  19: 453–459, 199221. Bishu K, Gricz KM, Chewaka S, Agarwal R:

Appropriateness of antihypertensive drug

therapy in hemodialysis patients. Clin J AmSoc Nephrol  1: 820–824, 2006

22. Ertürk S, Ertug AE, Atesx K, Duman N, Aslan

SM, Nergisoglu G, Diker E, Erol C, KaratanO, Erbay B: Relationship of ambulatory

blood pressure monitoring data to echo-

cardiographic   ndings in haemodialysis

patients. Nephrol Dial Transplant 11:2050–2054, 1996

23. Lazar AE, Smith MC, Rahman M: Blood

pressure measurement in hemodialysis pa-

tients. Semin Dial  17: 250–254, 2004

24. Rahman M, Grif n V, Kumar A, Manzoor F,

Wright JT Jr, Smith MC: A comparison of 

standardized versus“usual” blood pressure

measurements in hemodialysis patients.

Am J Kidney Dis  39: 1226–1230, 2002

25. Inrig JK, Patel UD, Gillespie BS, Hasselblad V, Himmelfarb J, Reddan D, Lindsay RM,

Winchester JF, Stivelman J, TotoR, Szczech

LA: Relationship between interdialyticweight gain and blood pressure among

prevalent hemodialysis patients. Am J Kid-ney Dis  50: 108–118, 2007

26. Agarwal R: Volume-associated ambulatory

blood pressure patterns in hemodialysis

patients. Hypertension 54: 241–247, 2009

27. Thompson AM, Pickering TG: The role of ambulatory blood pressure monitoring in

chronic and end-stage renal disease.  Kid-

ney Int  70: 1000–1007, 2006

28. Santos SF, Mendes RB, Santos CA, Dorigo

D, Peixoto AJ: Prole of interdialytic bloodpressure in hemodialysis patients.   Am J 

Nephrol  23: 96–105, 2003

29. Mendes RB, Santos SF, Dorigo D, Mansoor 

GA, CrowleyST, White WB,Peixoto AJ:The

use of peridialysis blood pressure and in-tradialytic blood pressure changes in the

prediction of interdialytic blood pressure in

haemodialysis patients. Blood Press Monit 

8: 243–248, 2003

30. Rohrscheib MR, Myers OB, Servilla KS,

Adams CD, Miskulin D, Bedrick EJ, HuntWC, Lindsey DE, Gabaldon D, Zager PG;

DCI Medical Directors: Age-related blood

pressure patterns and blood pressure vari-ability among hemodialysis patients.  Clin J 

Am Soc Nephrol  3: 1407–1414, 2008

31. Argilés A, Mourad G, Mion C: Seasonal

changes in blood pressure in patients with

end-stage renal disease treated with he-

modialysis.  N Engl J Med  339: 1364–1370,

1998

32. Conion PJ, Walshe JJ, Heinle SK, Minda S,Krucoff M, Schwab SJ: Predialysis systolic

blood pressurecorrelates strongly withmean

24-hour systolic blood pressure and left ven-

tricular mass in stablehemodialysis patients. J Am Soc Nephrol  7: 2658–2663, 1996

33. Agarwal R, PeixotoAJ, Santos SF,Zoccali C:

Pre- and postdialysis blood pressures are

imprecise estimates of interdialytic ambu-

latory blood pressure.   Clin J Am Soc 

Nephrol  1: 389–398, 200634. K/DOQI Workgroup: K/DOQI clinical prac-

tice guidelines for cardiovascular disease indialysis patients. Am J Kidney Dis  45[Suppl

3]: S1–S153, 2005

35. Davenport A, Cox C, Thuraisingham R:Achieving blood pressure targets during

dialysis improves control but increases in-

tradialytic hypotension. Kidney Int  73: 759–764, 2008

36. Ifudu O, Dawood M, Homel P, FriedmanEA: Excess interdialytic weight gain pro-

vokes antihypertensive drug therapy in pa-

tients on maintenance hemodialysis.   Dial 

Transplant  26: 541, 1997

37. Iseki K, Nakai S, Shinzato T, Morita O,

Shinoda T, Kikuchi K, Wada A, Kimata N,

J Am Soc Nephrol 25:  1630–1646, 2014 Hypertension in ESRD   1641

www.jasn.org   BRIEF REVIEW

8/15/2019 1630.full

13/17

8/15/2019 1630.full

14/17

pressure. Clin J Am Soc Nephrol  6: 1684–

1691, 2011

76. Cirit M, AkçiçekF, TerziogluE, SoydasxC,OkE, Ozbasxli CF, Basxçi A, Mees EJ:  ‘Paradoxi-

cal’ rise in blood pressure during ultraltra-

tion in dialysis patients.   Nephrol Dial Transplant  10: 1417–1420, 1995

77. Agarwal R, Alborzi P, Satyan S, Light RP:Dry-weight reduction in hypertensive he-

modialysis patients (DRIP): A randomized,

controlled trial. Hypertension 53: 500–507,

200978. InrigJK, VanBurenP, KimC, Vongpatanasin

W, Povsic TJ, Toto R: Probing the mecha-

nisms of intradialytic hypertension: A pilot

study targeting endothelial cell dysfunc-

tion. Clin J Am Soc Nephrol  7: 1300–1309,

201279. Miller BW, Cress CL, Johnson ME, Nichols

DH, Schnitzler MA: Exercise during hemo-

dialysis decreases the use of antihyper-

tensive medications.  Am J Kidney Dis  3 9:

828–833, 200280. Kooman JP, van der Sande F, Leunissen K,

Locatelli F: Sodium balance in hemodialysis

therapy. Semin Dial  16: 351–355, 2003

81 . Krautz ig S, Janssen U, Koch KM,

Granolleras C, Shaldon S: Dietary salt re-

striction and reduction of dialysate sodiumto control hypertension in maintenance

haemodialysis patients.   Nephrol Dial 

Transplant  13: 552–553, 199882. Tomson CR: Advising dialysis patients to

restrict   uid intake without restricting so-

dium intake is not based on evidence and

is a waste of time. Nephrol Dial Transplant 

16: 1538–1542, 2001

83. Bibbins-Domingo K, Chertow GM, Coxson

PG, Moran A, Lightwood JM, Pletcher MJ,

Goldman L: Projected effect of dietary saltreductions on futurecardiovascular disease.

N Engl J Med  362: 590–599, 2010

84. Ozkahya M, Toz H, Qzerkan F, Duman S,Ok

E, Basci A, Mees EJ: Impact of volumecontrol on left ventricular hypertrophy in

dialysis patients.   J Nephrol  15: 655–660,

2002

85. Ogden DA: A double blind crossover com-

parison of high and low sodium dialysis.Proc Clin Dial Transplant Forum   8: 157–165, 1978

86. Cybulsky AV, Matni A, Hollomby DJ:Effectsof high sodium dialysate during mainte-

nance hemodialysis.   Nephron   41: 57–61,

198587. Daugirdas JT, Al-Kudsi RR, Ing TS, Norusis

MJ: A double-blind evaluation of sodium

gradient hemodialysis.   Am J Nephrol   5:

163–168, 1985

88. Barré PE, Brunelle G, Gascon-Barré M: A randomized double blind trial of dialysate

sodiums of145 mEq/L, 150 mEq/L, and155

mEq/L. ASAIO Trans  34: 338–341, 1988

89. Munoz Mendoza J, Sun S, Chertow GM,

Moran J, Doss S, Schiller B: Dialysate so-

dium and sodium gradient in maintenance

hemodialysis: A neglected sodium re-

striction approach?   Nephrol Dial Trans-

plant  26: 1281–1287, 201190. Flanigan M: Dialysate composition and he-

modialysis hypertension.   Semin Dial   17:

279–283, 200491. Santos SF, Peixoto AJ: Revisiting the di-

alysate sodium prescription as a tool for better blood pressure and interdialytic

weight gain management in hemodialysis

patients.  Clin J Am Soc Nephrol  3: 522–

530, 2008

92. de Paula FM, Peixoto AJ, Pinto LV, DorigoD, Patricio PJ, Santos SF: Clinical con-

sequences of an individualized dialysate

sodium prescription in hemodialysis pa-

tients. Kidney Int  66: 1232–1238, 2004

93. Manlucu J, Gallo K, Heidenheim PA,Lindsay RM: Lowering postdialysis plasma

sodium (conductivity) to increase sodium

removal in volume-expanded hemodialysis

patients: A pilot study using a biofeedback

software system. Am J Kidney Dis  56: 69–76, 2010

94. Sang GL, Kovithavongs C, Ulan R,

Kjellstrand CM: Sodium ramping in hemo-

dialysis: A study of benecial and adverse

effects. Am J Kidney Dis 29: 669–677, 1997

95. Song JH, Lee SW, Suh CK, Kim MJ: Time-averagedconcentration of dialysate sodium

relates with sodium load and interdialytic

weight gain during sodium-proling he-modialysis.  Am J Kidney Dis  40: 291–301,

2002

96. Davies S, Carlsson O, Simonsen O,

Johansson AC, Venturoli D, Ledebo I,

Wieslander A, Chan C, Rippe B: The effects

of low-sodium peritoneal dialysis   uids on

blood pressure, thirst and volume status.

Nephrol Dial Transplant   24: 1609–1617,2009

97. Stewart WK, Fleming LW: Blood pressure

control during maintenance haemodialysis

with isonatric (high sodium) dialysate.Postgrad Med J  50: 260–264, 1974

98. Sinha AD, Agarwal R: Can chronic volume

overload be recognized and prevented in

hemodialysis patients? The pitfalls of the

clinical examination in assessing volume

status. Semin Dial  22: 480–482, 200999. Agarwal R, Andersen MJ, Pratt JH: On the

importanceof pedal edema in hemodialysispatients.  Clin J Am Soc Nephrol  3: 153–

158, 2008

100. Bridges N, Jarquin-Valdivia AA: Use of theTrendelenburg position as the resuscitation

position:ToTornottoT? AmJCritCare 14:

364–368, 2005

101. Monnet X, Teboul JL: Passive leg raising.

Intensive Care Med  34: 659–663, 2008102. Vertes V, CangianoJL, Berman LB,GouldA:

Hypertension in end-stage renal disease. N

Engl J Med  280: 978–981, 1969

103. Kayikcioglu M, Tumuklu M, Ozkahya M,

Ozdogan O, Asci G, Duman S, Toz H, Can

LH, Basci A, Ok E: The benet of salt

restriction in the treatment of end-stage

renal disease by haemodialysis.  Nephrol 

Dial Transplant  24: 956–962, 2009104. Goldstein SL, Smith CM, Currier H: Non-

invasive interventions to decrease hospi-

talization and associated costs for pediatricpatients receiving hemodialysis. J Am Soc 

Nephrol  14: 2127–

2131, 2003105. Rodriguez HJ, Domenici R, Diroll A,

Goykhman I: Assessment of dry weight by

monitoring changes in blood volume dur-

ing hemodialysis using Crit-Line. Kidney Int 68: 854–861, 2005

106. Patel HP, Goldstein SL, Mahan JD, Smith B,

Fried CB, Currier H, Flynn JT: A standard,

noninvasive monitoring of hematocrit al-

gorithm improves blood pressure control in

pediatric hemodialysis patients.  Clin J AmSoc Nephrol  2: 252–257, 2007

107. Reddan DN, Szczech LA, Hasselblad V,

Lowrie EG, Lindsay RM, Himmelfarb J, Toto

RD, Stivelman J, Winchester JF, Zillman LA,

Califf RM, Owen WF Jr: Intradialytic bloodvolume monitoring in ambulatory hemodi-

alysis patients: A randomizedtrial. JAmSoc 

Nephrol  16: 2162–2169, 2005

108. Wizemann V, Wabel P, Chamney P, Zaluska

W, Moissl U, Rode C, Malecka-Masalska T,

Marcelli D: The mortality risk of over-hydration in haemodialysis patients.

Nephrol Dial Transplant   24: 1574–1579,

2009109. Inrig JK, Patel UD, Toto RD, Reddan DN,

Himmelfarb J, Lindsay RM, Stivelman J,

Winchester JF, Szczech LA: Decreased

pulse pressure during hemodialysis is as-

sociatedwith improved 6-month outcomes.

Kidney Int  76: 1098–1107, 2009

110. Shoji T, Tsubakihara Y, Fujii M, Imai E:

Hemodialysis-associated hypotension as anindependent risk factorfor two-yearmortality

in hemodialysis patients.   Kidney Int   66:

1212–1220, 2004

111. Tattersall J, Martin-Malo A, Pedrini L, BasciA,CanaudB, FouqueD, HaageP, Konner K,

Kooman J, Pizzarelli F, Tordoir J,

 Vennegoor M, Wanner C, ter Wee P,

 Vanholder R: EBPG guideline on dialysis

strategies.   Nephrol Dial Transplant   22

[Suppl 2]: ii5–ii21, 2007112. Foley RN, Gilbertson DT, Murray T, Collins

AJ: Long interdialytic interval and mortalityamong patients receiving hemodialysis. N

Engl J Med  365: 1099–1107, 2011

113. Charra B, Calemard E, Ruffet M, Chazot C,Terrat J-C, Vanel T, LaurentG: Survival as an

index of adequacyof dialysis. Kidney Int 41:

1286–1291, 1992

114. Brunet P, Saingra Y, Leonetti F, Vacher-Coponat H, Ramananarivo P, Berland Y:

Tolerance of haemodialysis: A randomized

cross-over trial of 5-h versus 4-h treatment

time. Nephrol Dial Transplant  11[Suppl 8]:

46–51, 1996

115. Chan CT, Floras JS, Miller JA, Richardson

RM, Pierratos A: Regression of left

J Am Soc Nephrol 25:  1630–1646, 2014 Hypertension in ESRD   1643

www.jasn.org   BRIEF REVIEW

8/15/2019 1630.full

15/17

ventricular hypertrophy after conversion to

nocturnal hemodialysis.   Kidney Int   61:

2235–2239, 2002116. Woods JD, Port FK, Orzol S, Buoncristiani

U, Young E, Wolfe RA, Held PJ: Clinical and

biochemical correlates of starting   “daily”hemodialysis.   Kidney Int   55: 2467–2476,

1999117. Beecroft JM, Hoffstein V, Pierratos A, Chan

CT, McFarlane P, Hanly PJ: Nocturnal hae-

modialysis increases pharyngeal size in pa-

tients with sleep apnoea and end-stagerenal disease. Nephrol Dial Transplant  23:

673–679, 2008

118. Chan CT, Jain V, Picton P, Pierratos A,

Floras JS: Nocturnal hemodialysis increases

arterial baroreex sensitivity and compli-

ance and normalizes blood pressure of hy-pertensive patients with end-stage renal

disease. Kidney Int  68: 338–344, 2005

119. Saad E, Charra B, Raj DS: Hypertension

control with daily dialysis.  Semin Dial  17:

295–298, 2004120. Culleton BF, Walsh M, Klarenbach SW,

Mortis G, Scott-Douglas N, Quinn RR,

TonelliM, Donnelly S, Friedrich MG, Kumar 

A, Mahallati H, Hemmelgarn BR, Manns BJ:

Effectof frequent nocturnal hemodialysis vs

conventional hemodialysis on left ventricu-lar mass and quality of life: A randomized

controlled trial.   JAMA   298: 1291–1299,

2007121. Chertow GM, Levin NW, Beck GJ, Depner 

TA, Eggers PW, Gassman JJ, Gorodetskaya

I, Greene T, James S, Larive B, Lindsay RM,

Mehta RL,MillerB, Ornt DB,Rajagopalan S,

Rastogi A, Rocco MV, Schiller B, Sergeyeva

O, Schulman G, Ting GO, Unruh ML, Star 

RA, Kliger AS; FHN Trial Group: In-center 

hemodialysis six times per week versusthree times per week.  N Engl J Med  363:

2287–2300, 2010

122. Agarwal R: Frequent versus standard he-

modialysis.  N Engl J Med   364: 975–976,author reply 976, 2011

123. Rocco MV, Lockridge RS Jr, Beck GJ,

Eggers PW, Gassman JJ, Greene T, Larive

B, Chan CT, Chertow GM, Copland M, Hoy

CD, Lindsay RM, Levin NW, Ornt DB,Pierratos A, Pipkin MF, Rajagopalan S,

Stokes JB, Unruh ML, Star RA, Kliger AS,

Kliger A, Eggers P, Briggs J, Hostetter T,Narva A, Star R, Augustine B, Mohr P, Beck

G, Fu Z, Gassman J, GreeneT, Daugirdas J,

Hunsicker L, Larive B, Li M, Mackrell J,Wiggins K, Sherer S, Weiss B, Rajagopalan

S, Sanz J, Dellagrottaglie S, Kariisa M, Tran

T, West J, Unruh M, Keene R, Schlarb J,

Chan C, McGrath-Chong M, Frome R,Higgins H,Ke S,MandaciO, OwensC, Snell

C, EknoyanG, Appel L, Cheung A, Derse A,

Kramer C, GellerN, Grimm R, Henderson L,

Prichard S, Roecker E, Rocco M, Miller B,

Riley J, SchuesslerR, Lockridge R, Pipkin M,

Pete rson C, Hoy C, Fensterer A,

SteigerwaldD, StokesJ, SomersD, HilkinA,

Lilli K, Wallace W, Franzwa B, Waterman E,

Chan C, McGrath-Chong M, Copland M,Levin A, Sioson L, Cabezon E, Kwan S,

Roger D, Lindsay R, Suri R, Champagne J,

Bullas R, Garg A, Mazzorato A, Spanner E,

Rocco M, Burkart J, Moossavi S, Mauck V,Kaufman T, Pierratos A, Chan W, Regozo K,

Kwok S; Frequent Hemodialysis Network(FHN) Trial Group: The effects of frequent

nocturnal home hemodialysis: The Fre-

quent Hemodialysis Network Nocturnal

Trial. Kidney Int  80: 1080–1091, 2011124. Twardowski ZJ: Treatment time and ultra-

ltration rate are more important in dialysis

prescription than small molecule clearance.

Blood Purif  25: 90–98, 2007

125. Katzarski KS, Charra B, Luik AJ, Nisell J,

Divino Filho JC, Leypoldt JK, LeunissenKM,LaurentG, Bergström J: Fluid state and

blood pressure control in patients treated

with longand short haemodialysis. Nephrol 

Dial Transplant  14: 369–375, 1999

126. Agarwal R, Bouldin JM, Light RP, Garg A:Probing dry-weight improves left ventricu-

lar mass index. Am J Nephrol  33: 373–380,

2011

127. Hörl MP, Hörl WH: Drug therapy for hy-

pertension in hemodialysis patients. Semin

Dial  17: 288–294, 2004128. Hayashi SY, Seeberger A, Lind B, Gunnes S,

Alvestrand A, do Nascimento MM, Lindholm

B, Brodin LA: Acute effects of low and highintravenous doses of furosemide on myocar-

dial function in anuric haemodialysispatients:

A tissue Doppler study. Nephrol Dial Trans-

plant  23: 1355–1361, 2008

129. Hoyer J, Schulte KL, Lenz T: Clinical phar-

macokinetics of angiotensin converting

enzyme (ACE) inhibitorsin renal failure. Clin

Pharmacokinet  24: 230–254, 1993130. Agarwal R, Weir MR:Dry-weight: A concept

revisited in an effort to avoid medication-

directed approaches for blood pressure

control in hemodialysis patients. Clin J AmSoc Nephrol  5: 1255–1260, 2010

131. Zannad F, Kessler M, Lehert P, Grünfeld

JP, Thuilliez C, Leizorovicz A, Lechat P:

Prevention of cardiovascular events in end-

stage renal disease: Results of a randomizedtrial of fosinopril and implications for fu-

ture studies.   Kidney Int   70: 1318–1324,

2006132. Takahashi A, Takase H, Toriyama T, Sugiura

T,Kurita Y,UedaR, DohiY: Candesartan,an

angiotensin II type-1 receptor blocker, re-duces cardiovascular events in patients on

chronic haemodialysis—a randomized

study.  Nephrol Dial Transplant  21: 2507–2512, 2006

133. Cice G, Ferrara L, D’Andrea A, D’Isa S, Di

Benedetto A, Cittadini A, Russo PE, Golino

P, Calabrò R: Carvedilol increases two-year 

survivalin dialysis patients with dilated

cardiomyopathy: A prospective, placebo-

controlled trial. J AmCollCardiol 41:1438–

1444, 2003

134. Heerspink HJ, Ninomiya T, Zoungas S, de

Zeeuw D, Grobbee DE, Jardine MJ,Gallagher M, Roberts MA, Cass A, Neal B,

Perkovic V: Effect of lowering blood pres-

sure on cardiovascular events and mortality

in patients on dialysis: A systematic reviewand meta-analysis of randomised con-

trolled trials. Lancet  373: 1009–

1015, 2009135. Agarwal R, Sinha AD: Cardiovascular pro-

tectionwith antihypertensivedrugs in dialysis

patients: Systematic review and meta-analysis.

Hypertension 53: 860–866, 2009136. Agarwal R, Sinha AD, Pappas MK, Abraham

TN, Tegegne GG: Hypertension in hemo-

dialysis treated with atenolol or lisinopril: A 

randomized controlled trial.   Nephrol Dial 

Transplant  29: 672–681, 2014

137. Buckner FS, Eschbach JW, Haley NR,Davidson RC, Adamson JW: Hypertension

following erythropoietin therapy in anemic

hemodialysis patients.  Am J Hypertens  3:

947–955, 1990

138. EschbachJW, Kelly MR,Haley NR, Abels RI,Adamson JW: Treatment of the anemia of 

progressive renal failure with recombinant

human erythropoietin.  N Engl J Med  321:

158–163, 1989

139. Eschbach JW, Abdulhadi MH, Browne JK,

Delano BG, Downing MR, Egrie JC, EvansRW, Friedman EA, Graber SE, Haley NR,

Korbet S, Krantz SB, Lundin AP, Nissenson

AR, Ogden DA, Paganini EP, Rader B,Rutsky EA, Stivelman J, Stone WJ, Teschan

P, Van Stone JC, Van Wyck DB, Zuckerman

K, Adamson JW: Recombinant human

erythropoietin in anemic patients with end-

stage renal disease. Results of a phase III

multicenter clinical trial.   Ann Intern Med 

111: 992–1000, 1989

140. AbrahamPA, Macres MG:Bloodpressure inhemodialysis patients during amelioration

of anemia with erythropoietin.   J Am Soc 

Nephrol  2: 927–936, 1991

141. Kaupke CJ, Kim S, Vaziri ND: Effect of erythrocyte mass on arterial blood pressure

in dialysis patients receiving maintenance

erythropoietin therapy. J Am Soc Nephrol 

4: 1874–1878, 1994

142. Lebel M, Kingma I, Grose JH, Langlois S:Hemodynamic and hormonal changes dur-

ing erythropoietin therapy in hemodialysis

patients. J AmSocNephrol 9:97–

104,1998143. Wang XQ, Vaziri ND: Erythropoietin de-

presses nitric oxide synthase expression by

human endothelial cells.  Hypertension 33:894–899, 1999

144. Bode-Böger SM, Böger RH, Kuhn M,

Radermacher J, Frölich JC: Recombinant

human erythropoietin enhances vasocon-strictor tone via endothelin-1 and constrictor 

prostanoids. Kidney Int 50: 1255–1261, 1996

145. Carlini R, Obialo CI, Rothstein M: In-

travenous erythropoietin (rHuEPO) admin-

istration increases plasma endothelin and

blood pressure in hemodialysis patients.

Am J Hypertens  6: 103–107, 1993

1644   Journal of the American Society of Nephrology J Am Soc Nephrol 25:  1630–1646, 2014

BRIEF REVIEW   www.jasn.org

8/15/2019 1630.full

16/17

146. Carlini RG, Dusso AS, Obialo CI, Alvarez

UM, Rothstein M: Recombinant human

erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells.  Kidney Int  43:

1010–1014, 1993

147. Eggena P, Willsey P, Jamgotchian N,Truckenbrod L, Hu MS, Barrett JD, Eggena

MP, Clegg K, Nakhoul F, Lee DB: Inuenceof recombinant human erythropoietin on

blood pressure and tissue renin-angiotensin

systems.   Am J Physiol   261: E642–E646,

1991148. Hand MF, Haynes WG, Johnstone HA,

Anderton JL, Webb DJ: Erythropoietin

enhances vascular responsiveness to nor-

epinephrine in renal failure. Kidney Int  48:

806–813, 1995

149. Amar J, Vernier I, Rossignol E, Lenfant V,Conte JJ, Chamontin B: Inuence of nyc-

themeral blood pressure pattern in treated

hypertensive patients on hemodialysis.

Kidney Int  51: 1863–1866, 1997

150. Canadian Erythropoietin Study Group: Ef-fect of recombinant human erythropoietin

therapy on blood pressure in hemodialysis

patients. Am J Nephrol  11: 23–26, 1991

151. Lebel M, Kingma I, Grose JH, Langlois S:

Effect of recombinant human erythropoie-

tintherapy on ambulatory blood pressure innormotensive and in untreated borderline

hypertensive hemodialysis patients.  Am J 

Hypertens  8: 545–551, 1995152. Ishimitsu T, Tsukada H, Ogawa Y, Numabe

A, Yagi S: Genetic predisposition to hyper-

tension facilitates blood pressure elevation

in hemodialysis patients treated with

erythropoietin.   Am J Med   94: 401–406,

1993

153. Zoccali C, Benedetto FA, Tripepi G,

Cambareri F, Panuccio V, Candela V,Mallamaci F, Enia G, Labate C, Tassone F:

Nocturnal hypoxemia, night-day arterial

pressure changes and left ventricular ge-

ometry in dialysis patients.  Kidney Int  53:1078–1084, 1998

154. Unruh ML, Sanders MH, Redline S, Piraino

BM, Umans JG, Hammond TC, Sharief I,

Punjabi NM, Newman AB: Sleep apnea in

patients on conventional thrice-weeklyhemodialysis: Comparison with matched

controls from the Sleep Heart Health

Study. J Am Soc Nephrol  17: 3503–

3509,2006

155. Abdel-KaderK, DoharS, Shah N, JhambM,

Reis SE, Strollo P, Buysse D, Unruh ML:Resistant hypertension and obstructive

sleep apnea in the setting of kidney dis-

ease. J Hypertens  30: 960–966, 2012

156. Park J, Campese VM: Resistant hypertensionand obstructive sleep apnea in end-stage

renal disease.  J Hypertens   30: 880–881,

2012

157. Tada T, Kusano KF, Ogawa A, Iwasaki J,

SakuragiS, Kusano I, Takatsu S, Miyazaki M,

Ohe T: The predictors of central and ob-

structive sleep apnoea in haemodialysis

patients. NephrolDial Transplant 22:1190–

1197, 2007

158. Dorhout Mees EJ: Hypertension in haemo-dialysis patients: Who cares? Nephrol Dial 

Transplant  14: 28–30, 1999

159. Duranti E, Imperiali P, Sasdelli M: Ishypertension a mortality risk factor in di-

alysis?   Kidney Int Suppl   55: S173–

S174,1996

160. Fleischmann EH, Bower JD, Salahudeen

AK: Are conventional cardiovascular risk

factors predictive of two-year mortality inhemodialysis patients?   Clin Nephrol   56:

221–230, 2001

161. Foley RN, Parfrey PS, Harnett JD, Kent GM,

Murray DC, Barre PE: Impact of hyperten-

sion on cardiomyopathy, morbidity and

mortality in end-stage renal disease.Kidney Int  49: 1379–1385, 1996

162. Kalantar-Zadeh K, Kilpatrick RD, McAllister 

CJ, Greenland S, Kopple JD: Reverse epi-

demiology of hypertension and cardiovas-

cular death in hemodialysis patients: The58th annual fall conference and scientic

sessions.. Hypertension 45: 811–817, 2005

163. Mazzuchi N, Carbonell E, Fernández-Cean

J: Importance of blood pressure control in

hemodialysis patientsurvival. Kidney Int 58:

2147–2154, 2000164. Salem MM, Bower J: Hypertension in the

hemodialysis population: Any relation to

one-year survival? AmJKidneyDis 28:737–740, 1996

165. Kawamura M, Fijimoto S, Hisanaga S,

 Yamamoto Y, Eto T: Incidence, outcome,

and risk factors of cerebrovascularevents in

patients undergoing maintenance hemo-

dialysis. AmJ Kidney Dis 31:991–996,1998

166. van derSande FM,Hermans MM,Leunissen

KM, KoomanJP: Noncardiac consequencesof hypertension in hemodialysis patients.

Semin Dial  17: 304–306, 2004

167. Savazzi GM, Cusmano F, Bergamaschi E,

 Vinci S, Allegri L, Garini G: Hypertension asan etiopathological factor in the de-

velopment of cerebral atrophy in hemo-

dialyzedpatients. Nephron 81:17–24,1999

168. Takeda A, Toda T, Fujii T, Shinohara S,

Sasaki S, Matsui N: Discordance of in-

uence of hypertension on mortality and

cardiovascular risk in hemodialysis patients.

Am J Kidney Dis  45: 112–

118, 2005169. DeLimaJJ,Lopes HF,GrupiCJ, Abensur H,

Giorgi MC, Krieger EM, Pileggi F: Blood

pressure inuences the occurrence of complex ventricular arrhythmia in hemodi-

alysis patients.   Hypertension   26: 1200–1203, 1995

170. Tomita J, Kimura G, Inoue T, Inenaga T,Sanai T, Kawano Y, Nakamura S, Baba S,

Matsuoka H, OmaeT: Role of systolicblood

pressure in determining prognosis of he-

modialyzed patients. Am J Kidney Dis  25:

405–412, 1995

171. Port FK, Hulbert-Shearon TE, Wolfe RA,

Bloembergen WE, Golper TA, Agodoa LY,

 Young EW: Predialysis blood pressure and

mortality risk in a national sample of main-

tenance hemodialysis patients.  Am J Kid-ney Dis  33: 507–517, 1999

172. Salem MM: Hypertension in the haemo-

dialysis population: Any relationship to2-years survival?   Nephrol Dial Transplant 

14: 125–

128, 1999173. Zager PG, Nikolic J, Brown RH, Campbell

MA, Hunt WC, Peterson D, Van Stone J,

Levey A, Meyer KB, Klag MJ, Johnson HK,

Clark E, Sadler JH, Teredesai P:   “U” curve

association of blood pressure and mortalityin hemodialysis patients. Medical Directors

of Dialysis Clinic, Inc.  Kidney Int  54: 561–

569, 1998

174. Lacson E Jr, Lazarus JM: The association

between blood pressure and mortality inESRD-not different from the general pop-

ulation? Semin Dial  20: 510–517, 2007

175. Li Z, Lacson E Jr, Lowrie EG, Ofsthun NJ,

Kuhlmann MK, Lazarus JM, Levin NW: The

epidemiology of systolic blood pressureand death risk in hemodialysis patients. Am

J Kidney Dis  48: 606–615, 2006

176. Charra B: Control of blood pressure in long

slow hemodialysis.   Blood Purif   12: 252–

258, 1994

177. Stidley CA, Hunt WC, Tentori F, Schmidt D,Rohrscheib M, Paine S, Bedrick EJ, Meyer 

KB, Johnson HK, Zager PG; Medical Direc-

tors of Dialysis Clinic Inc: Changing re-lationship of blood pressure with mortality

over time among hemodialysis patients.  J 

Am Soc Nephrol  17: 513–520, 2006

178. Degoulet P, Legrain M, Réach I, Aimé F,

Devriés C, Rojas P, Jacobs C: Mortality risk

factors in patients treated by chronic he-

modialysis. Report of the Diaphane collab-

orative study. Nephron 31: 103–110, 1982179. Groothoff J, Gruppen M, de Groot E,

Offringa M: Cardiovascular diseaseas a late

complication of end-stage renal disease in

children.  Perit Dial Int  25[Suppl 3]: S123–S126, 2005

180. Parekh RS, Carroll CE, Wolfe RA, Port FK:

Cardiovascular mortality in children and

young adults with end-stage kidney dis-

ease. J Pediatr  141: 191–197, 2002

181. Mitsnefes M, Stablein D: Hypertension inpediatric patients on long-term dialysis:

a report of the North American Pediat-ric Renal Transplant Cooperative Study

(NAPRTCS). AmJKidneyDis 45:309–315,

2005182. Halbach SM, Martz K, Mattoo T, Flynn J:

Predictors of blood pressure and its control

in pediatric patients receiving dialysis.   J 

Pediatr  160: 621–625, e1, 2012

183. Kramer AM, van Stralen KJ, Jager KJ,Schaefer F, Verrina E, Seeman T, Lewis MA,

Boehm M, Simonetti GD, Novljan G,

Groothoff JW: Demographics of blood

pressure and hypertension in children on

renal replacement therapy in Europe. Kid-

ney Int  80: 1092–1098, 2011

J Am Soc Nephrol 25:  1630–1646, 2014 Hypertension in ESRD   1645

www.jasn.org   BRIEF REVIEW

8/15/2019 1630.full

17/17

184. Mitsnefes MM, Daniels SR, Schwartz SM,

Khoury P, Strife CF: Changes in left ven-

tricular mass in children and adolescentsduring chronic dialysis. Pediatr Nephrol 16:

318–323, 2001

185. Bakkaloglu SA, Borzych D, Soo Ha I,Serdaroglu E, Büscher R, Salas P, Patel H,

Drozdz D, Vondrak K, Watanabe A, Villagra J, Yavascan O, Valenzuela M, Gipson D, Ng KH,

Warady BA, Schaefer F; International Pediatric

Peritoneal DialysisNetwork: Cardiacgeometry

in children receiving chronic peritoneal di-alysis:Findings fromthe International Pediatric

Peritoneal Dialysis Network (IPPN) registry.

Clin J Am Soc Nephrol  6: 1926–1933, 2011

186. Mitsnefes MM, Daniels SR, Schwartz SM,

Meyer RA, Khoury P, Strife CF: Severe left

ventricular hypertrophy in pediatric dialysis:

Prevalence and predictors. Pediatr Nephrol 

14: 898–902, 2000

187. Hölttä T, Happonen JM, Rönnholm K,Fyhrquist F, Holmberg C: Hypertension,

cardiac state, and the role of volume over-

load during peritoneal dialysis.   Pediatr Nephrol  16: 324–331, 2001

188. Schärer K, Schmidt KG, Soergel M: Cardiacfunction and structure in patients with

chronic renal failure.  Pediatr Nephrol   13:

951–965, 1999

189. National High Blood Pressure EducationProgram Working Group on High Blood

Pressure in Children and Adolescents: The

fourth report on the diagnosis, evaluation,

and treatment of high blood pressure in

children and adolescents.   Pediatrics   114

[Suppl 4th Report]: 555–576, 2004

190. Kidney Disease Outcomes Quality Initiative

(K/DOQI): K/DOQI clinical practice guide-lines on hypertension and antihypertensive

agents in chronic kidney disease.   Am J 

Kidney Dis  43[Suppl 1]: S1–S290, 2004

191. Ulinski T, Genty J, Viau C, Tillous-Borde I,Deschênes G: Reduction of left ventricular 

hypertrophy in children undergoing hemodi-alysis. Pediatr Nephrol  21: 1171–1178, 2006

192. Thalange NK, Foster PJ, Gill MS, Price DA,

Clayton PE: Model of normal prepubertal

growth. Arch Dis Child  75: 427–431, 1996193. Paglialonga F, Ardissino G, Galli MA,

Scar a RV, Testa S, Edefonti A: Bio-

impedance analysis and cardiovascular 

status in pediatric patients on chronic he-

modialysis.  Hemodial Int  16[Suppl 1]: S20–

S25, 2012

BRIEF REVIEW   www.jasn.org