Paper 3 Management of Hypertension in DIALYSIS

8/17/2019 Paper 3 Management of Hypertension in DIALYSIS

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Management of Hypertension inHemodialysis PatientsC. Venkata S. Ram, MD, and Andrew Z. Fenves, MD

Corresponding author C. Venkata S. Ram, MD1420 Viceroy Drive, Dallas, TX 75235, USA.E-mail: [email protected]

Current Hypertension Reports 2009, 11: 292 –298Current Medicine Group LLC ISSN 1522-6417Copyright © 2009 by Current Medicine Group LLC

Hypertension is very common in patients withchronic kidney disease and is present in most patientswith end-stage renal disease (ESRD). Hypertensionis largely responsible for premature cardiovasculardisease in dialysis patients. The pathophysiologyof hypertension in ESRD is complex, and multiplemechanisms are likely involved in blood pressure dys-regulation in patients on hemodialysis. Some of thesepatients demonstrate resistant hypertension. Aggres-sive control of hypertension in ESRD/dialysis ismandatory. Generally, nonpharmacologic treatmentsare not enough to achieve the goal blood pressurelevels in dialysis patients. Multiple antihypertensivedrugs are often necessary. Drugs that block the renin-angiotensin system offer a number of advantages forpatients with chronic kidney disease or ESRD, butadditional drug classes are often needed to achieveeffective blood pressure control in dialysis patients.Physicians treating hypertension in dialysis patientsshould be familiar with the pharmacokinetic prop-erties of antihypertensive drugs in renal failure andchoose the dosages accordingly. Vigorous control ofhypertension is recommended to reduce the diseaseburden in patients with ESRD.

IntroductionSystemic hypertension in patients undergoing chronicdialysis presents a major therapeutic challenge in clinicalmedicine. Because it is a cause as well as a consequence ofchronic kidney disease (CKD) and end-stage renal disease(ESRD), hypertension not only is prevalent in patientsundergoing dialysis but also is a critical contributor toexcessive cardiovascular morbidity and mortality in thesehigh-risk patients. Hypertension occurs in more than 80%of patients who have ESRD [1]. The prevalence and degreeof hypertension is steadily increasing in patients undergo-ing hemodialysis or chronic ambulatory peritoneal dialysis.

Despite advances in the physiology and pharmacology ofblood pressure control mechanisms, hypertension remainspoorly controlled in patients with ESRD (Table 1). Uncon-trolled hypertension contributes to excessive cardiovascularmorbidity and mortality in dialysis patients.

Systemic hypertension is a risk factor for vascular disease,accelerated progression of atherosclerosis, left ventricularhypertrophy, and cardiac dysfunction. Cardiovascular dis-ease accounts for the high mortality rate in patients withESRD, and hypertension is the most powerful link to cardio-vascular disease in this population [2]. The presence of otherrisk factors for cardiovascular disease, such as diabetes andhyperlipidemia, imposes further risk in patients with ESRD.

Pathophysiologic FactorsThe etiology of hypertension in ESRD is complex andmultifactorial. With the establishment and progression ofhypertension in ESRD, the hemodynamic milieu changesdramatically with complicated interactions among themechanisms of circulatory control. Because of the complexinterplay of various pathophysiologic processes, treatmentof hypertension in ESRD is extremely dif cult and thetherapeutic response is often unpredictable. In a substan-tial number of patients on dialysis, removal of excess uidand achievement of dry weight improves blood pressurecontrol. Patients with ESRD demonstrate a rise in cardiacoutput as a reaction to anemia. In normotensive patientswith ESRD, the rise in cardiac output is accompanied bya fall in peripheral vascular resistance; in hypertensivepatients, however, this reciprocal adaptive change fails tooccur, culminating in a blood pressure rise. The discus-sion in this article applies to hemodialysis patients butnot to peritoneal dialysis patients, with some exceptions.

Blood pressure control in patients undergoing peritonealdialysis is less dif cult than in hemodialysis patients.

Extracellular uid volume expansionThe volume of extracellular uid (ECF) is probably themost important determinant of hypertension in ESRDpatients [3–7]. ECF expansion is not always accompaniedby detectable edema. ECF volume retention leads to anincrease in cardiac output against the setting of inappro-priate systemic vascular resistance, with the ultimate resultof rising blood pressure. This hemodynamic imbalanceis further complicated by the failure to inhibit vasocon-


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Management of Hypertension in Hemodialysis Patients I Ram and Fenves I 293

strictor mechanisms such as the renin angiotensin system(RAS) and sympathetic nervous system (SNS) [8,9]. Theultra ltration component of dialysis improves the bloodpressure in ESRD (at times, rather dramatically), re ect-ing the “volume-dependent” factor in these patients. Insome patients, however, it may take frequent dialysis toproduce an improvement in blood pressure. Hence, evenin so-called volume-dependent hypertension, removal ofECF alone may not explain the blood pressure dynamicsin ESRD. Nevertheless, achievement and maintenanceof “dry weight” is a crucial component of hypertensionmanagement in ESRD. Inadequate removal of ECF vol-ume is major cause of resistant hypertension in dialysispatents. Dry weight is not a xed measure and is variable.It is impossible to keep the patient “dry” constantly; theidea is to prevent volume overload as a pathogenetic fac-tor for persistent hypertension. ECF overload in ESRD isdue to the loss of renal excretory function and the absenceof vasodilatory renoprival factors such as prostaglandins.Because not only the volume factor but also the activityof vasoconstrictor forces such as RAS and SNS mediateblood pressure homeostasis, inappropriate activity of SNSand RAS (high or even normal) in the context of volumeoverload clearly contributes to the onset and developmentof hypertension in ESRD patients on dialysis.

The role of the RAS pathway in the genesis of ESRDhypertension is evident from the effect iveness of bilateralnephrectomy, which instantly removes the main source ofrenin in dialysis patients. There is an inverse correlationbetween systemic vascular resistance and Na + /K+ adenos-ine triphosphatase (ATPase) activity. In dialysis patients,there is increased secretion of ouabain-like inhibitorsof Na + /K+ ATPase activity. When the actions of Na + /K+

ATPase are inhibited in the vascular smooth muscle,the intracellular Na + level and the cytosolic Ca +2 levelincrease, leading to signi cant vasoconstriction. Regard-less of the mechanism of vasoconstriction, removal ofECF volume and attainment of dry weight often improveblood pressure control in dialysis patients. It is worthremembering that the degree of volume overload is clas-sically re ected by an increase in blood pressure ratherthan by the appearance of frank edema. It is importantto emphasize to patients that the therapeutic gains fromdialysis can be sustained only if salt intake is curtailedbetween dialysis sessions.

Renin-angiotensin system activationThe role of the RAS in the etiology of hypertension inESRD is well established [8,9]. In hemodialysis patientswith ESRD, there is an abnormal relationship betweenblood volume, exchangeable sodium, and plasma reninactivity. Bilateral nephrectomy improves blood pressurecontrol in dialysis patients with severe hypertension, pre-

sumably by removing the basic biologic source of renin.Indirect evidence for the participation of the RAS inhypertension associated with ESRD is the prompt thera-peutic response seen with the use of drugs that block theRAS. It is also possible that aldosterone may play a role inthe genesis of hypertension in dialysis patients. Failure tosuppress the RAS despite volume expansion identi es thismechanism as a principal mediator of vasoconstrictionand blood pressure elevation in patients on dialysis.

Sympathetic nervous system activityIt is well known that uremia and ESRD are associatedwith enhanced SNS activity [10–12]; measurement ofperoneal nerve activity in ESRD has con rmed the roleof SNS activation in this setting [13]. The afferent signalfor SNS activity most likely resides in the kidney itself,as the nerve activity is diminished in the anephric state.Although plasma concentrations of catecholamines areelevated in ESRD, this nding must be interpreted withcaution because of altered metabolism and kinetics ofepinephrine and norepinephrine in CKD. The increaseof SNS activity is triggered by an excitatory signalarising in the failing kidney; uremia stimulates chemo-sensitive afferent nerves in the kidney. Selective surgicalremoval of affected renal nerves prevents hypertensionin experimental renal injury. Hemodialysis patients withbilateral nephrectomy show the same level of sympa-thetic discharge as normal controls. Another possibleneurogenic mechanism in anemic patients is reducedcentral dopaminergic tone. In chronic renal failure, thebiologic actions of dopamine are attenuated, resultingin a re exive increase in SNS activity. Abnormal vagaltone and reduced baroreceptor sensitivity have also beenimplicated as mechanisms of hypertension in ESRD thatinvolve SNS activation.

Erythropoietin useTherapeutic application of recombinant human erythro-

poietin (rHuEPO) has been a signi cant advance in themanagement of anemia in ESRD/hemodialysis patients.Unfortunately, rHuEPO increases blood pressure bycausing vasoconstriction and increasing the blood viscos-ity (Table 2) [14–16]; correction of anemia also preventshypoxia-mediated vasodilatation. The rise in blood pres-sure with the use of rHuEPO occurs within 2 to 12 weeksof therapy. Rapid correction of anemia and a prior his-tory of hypertension are important predisposing factors.Both anemia and its overcorrection can be detrimental, soevery attempt should be made to keep the maximum levelof hemoglobin between 10 and 12 g/dL.

Table 1. Reasons for lack of control ofhypertension in dialysis patientsStaff satisfaction with level of blood pressureInsufcient attention to lifestyle modicationPatient noncompliance with salt and uid intakeInadequate ultraltration

Inadequate prescription of medicationsUnderlying secondary form of hypertension


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294 I The Therapeutic Trials

The risk of hypertension is higher in patients receivingrHuEPO intravenously rather than subcutaneously, andthe degree of hypertension is dose-dependent. Treatmentwith rHuEPO increases blood viscosity, blood volume,plasma endothelin, and catecholamines, and it may alsocause direct vasoconstriction. The bene ts of rHuEPOin correcting anemia outweigh the risk of hypertension,however, as the hypertension can be controlled by dialysisand antihypertensive drugs. The dosage of rHuEPO canbe reduced with the use of adjunct therapies such as iron,thus minimizing the risk of hypertension.

Divalent ions and parathyroid hormoneIntracellular levels of calcium are increased in patientswith chronic renal failure, and there is a direct patho-physiologic correlation between intracellular calcium andblood pressure levels in dialysis patients with hyperten-sion. Studies have shown a positive correlation betweenintracellular and platelet calcium, serum parathyroidhormone (PTH), and blood pressure levels in patientswith chronic renal failure [17–19]. Hypercalcemia is morelikely to raise blood pressure in the presence of increasedPTH levels because of vasoconstriction, not cardiac out-put changes. Exogenous use of vitamin D analogues andoral calcium supplementation are some factors contribut-ing to hypercalcemia in ESRD. Augmentation of RAS andSNS activity may also raise cytosolic concentrations ofcalcium. Correction of hyperparathyroidism by vitaminD administration or parathyroidectomy may lower blood

pressure in patients with ESRD. PTH appears to play arole in the development of hypertension associated withhypercalcemia in ESRD.

Endothelial factorsThe role of endothelial cells in regulating vasomotor toneand systemic vascular resistance is well established. Theavailability and actions of endothelium-derived relaxationfactor—now identi ed as nitric oxide (NO)—governs thestate of vasoactive tone [20]. An absolute or relative de -ciency of NO leads to a rise in the blood pressure level.This mechanism may play a role in the development of

dialysis-associated hypertension [21,22]. The extentto which an NO defect contributes to hypertension inchronic renal failure is not rmly established. An endog-enous inhibitor of NO, asymmetric dimethylarginine,accumulates in ESRD and thus may predispose to hyper-tension. Increased function of the SNS also may inhibitNO availability.

An endothelium-derived vasoconstricting factor,endothelin-1 (ET-1), is expressed in the blood vessels.ET-1 promotes vasoconstriction and brosis. It hasbeen suggested that hypertensive ESRD patients havehigher levels of ET-1 than normotensive patients. It isof interest to note that ET-1 levels are more affectedin hemodialysis patients than in peritoneal dialysispatients. Whether directly or indirectly, ET-1 maybe abnormally regulated in hypertensive patients ondialysis [23,24].

ProstaglandinsBecause renal prostaglandins and prostacyclin causevasodilatation, a de ciency of these mediators in ESRDmay increase blood pressure. They also offset vasocon-strictor in uences. Hence, renal prostaglandins may playa pathologic role in blood pressure regulation in patientswith ESRD.

Treatment of HypertensionTreating hypertension in the dialysis patient can bedif cult, and a number of hemodynamic and pharmaco-logic factors must be considered. As in the managementof general hypertension, nonpharmacologic approachesshould be attempted rst, before resorting to drugtherapy [25,26]. Lifestyle modi cation and hygienicmeasures to maintain cardiovascular health should beimplemented. If these measures fail or are inadequate,appropriate antihypertensive drugs should be chosenfor the dialysis patient. Achievement and maintenanceof optimal dry weight through appropriate sodium and

uid restriction and dialysis frequency is a critical stepfor blood pressure control [27]. After initiating dialy-sis, dry weight should be accomplished over a periodof 6 to 8 weeks, keeping in mind that the negative uidbalance should not exceed 1 to 2 kg per week. Exces-sive ultra ltration may result in hypoperfusion and

ischemia. It is impossible to de ne dry weight precisely,but in clinical terms, dry weight can be characterized asthe body weight at the end of d ialysis below which fur-ther ultra ltration causes hypotension. Estimation ofdry weight is a practical problem; several methods havebeen proposed but none are feasible in clin ical practice.Nevertheless, uid balance is of clinical importance inthe dialysis patient [28–30]. Although aggressive ultra-

ltration is sometimes indicated (for congestive heartfailure, complicated hypertension, etc.), overzealousdialysis may result in paradoxical hypertension becauseof activation of the RAS and SNS.

Table 2. Factors in the pathogenesis ofhypertension in ESRD patients on erythropoietinIncreased blood viscosityIncreased blood volumeIncreased total peripheral resistanceLoss of hypoxic vasodilation

Enhanced sensitivity to circulatingcatecholamines and angiotensin II

Direct vasoconstrictor effectIncreased cytosolic calciumStimulation of endothelinESRD—end-stage renal disease.


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Unless hypertension is severe, antihypertensive drugtherapy need not be instituted until dry weight is achieved.In patients taking antihypertensive drugs, the doses canbe reduced while dry weight is achieved through dialysis.For many patients, dry weight alone is enough to achievegoal blood pressure. The problem is that the blood pres-sure often goes up in the interdialytic periods. Judicious

use of antihypertensive drugs is indicated to manage inter-dialytic hypertension. Carefully monitored ultra ltrationis the most important determinant of effective bloodpressure control in the dialysis patient. Because of the dif-

culty of estimating dry weight, nephrologists must applytheir judgment and clinical experience. It is important forpatients to maintain a high level of nutrition to comple-ment the bene ts of hemodialysis.

When the blood pressure cannot be controlled withproper ultra ltration alone, antihypertensive drugsshould be used in dialysis patients. In general, except fordiuretics, the pharmacologic options for dialysis patientsdo not differ very much from those used to treat primaryhypertension. From a pathophysiologic standpoint, drugsthat block the RAS are desirable to treat hypertension inthe dialysis patient, but in our experience, this approachalone is not enough; multiple drugs are often necessary.Physicians should be cognizant of the altered pharmaco-kinetics of antihypertensive drugs in renal failure andshould choose drugs and dosages accordingly.

Renin-angiotensin system blockersBecause several factors mediating hemodynamic variablesin ESRD are governed by the activity of the RAS, phar-macologic approaches to block this system are widelyapplied to treat hypertension in dialysis patients [31–33].Interruption of the RAS with angiotensin-convertingenzyme (ACE) inhibitors or angiotensin receptor block-ers (ARBs) reduces systemic vascular resistance withoutaffecting cardiac output. RAS blockers have been shownto be not only effective but also advantageous in patientswith CKD, but whether the same observation can betranslated to ESRD has not been proven. Effective inhibi-tion of the RAS along with dialysis causes regression ofleft ventricular hypertrophy.

ACE inhibitorsACE inhibitors may decrease the circulating levels of

angiotensin (and aldosterone) and thus offset the vaso-constrictor consequences of inappropriate RAS activationin patients with ESRD. An advantage of ACE inhibitors(in contrast to direct vasodilators) is inhibition of thecounter-regulatory compensatory systems like the SNS.Hence, the fall in blood pressure, if achieved, is likely to bemaintained with continued ACE inhibitor therapy. More-over, ACE inhibitors improve (or do not worsen) insulinsensitivity, a bene t in patients with coexisting diabetes.Most patients on dialysis require multiple antihyperten-sive drugs, one of which should be an RAS blocker if thereare no contraindications or adverse effects.

ACE inhibitors are generally well tolerated. Possibleadverse effects include cough, angioedema, rash, and(rarely) leukopenia. A notable side effect of ACE inhibitorsis the worsening of anemia in dialysis patients; aggrava-tion of anemia by ACE inhibitors in CKD is unpredictable(or may be unrecognized) because of its chronic, insidiousnature and other contributing factors to anemia develop-

ment in ESRD. Inhibition of angiotensin II activity mayblock signal transduction of erythropoietin at the cellu-lar level. Anaphylactic reactions have been reported withACE inhibitors in ESRD patients undergoing dialysis witha high- ux capillary dialyzer.

Angiotensin receptor blockersARBs pharmacologically block the effects of angiotensinII on the blood vessels and other tissues. The dominantmechanism of ARBs in the treatment of hypertension is theinhibition of angiotensin II–mediated vasoconstriction;to some extent, they also modulate SNS tone indirectly.ARBs are extremely useful in patients with CKD, espe-cially those with diabetic nephropathy and proteinuricdisorders [34–36]. However, whether these ndings canbe extrapolated to patients with ESRD is not established.Nevertheless, like ACE inhibitors, ARBs also exert a num-ber of hemodynamic and nonhemodynamic advantagesin managing hypertension associated with ESRD. UnlikeACE inhibitors, however, ARBs are unlikely to causecough, rash, or angioedema, and anaphylactic reactionsto ARBs are also rare in patients undergoing dialysis witha high- ux capillary dialyzer.

Calcium channel blockersIntracellular calcium exerts a number of actions onblood pressure control mechanisms by its effects on vas-cular smooth muscle and other pressor systems (SNS,RAS, etc.). Calcium channel blockers (CCBs) block thevoltage-dependent calcium channels, thereby inhibitingvascular smooth muscle activity. Because of their provenantihypertensive properties, CCBs are widely used inpatients on hemodialysis [37–39]. The dihydropyridine(DHP) subclass of CCBs (nifedipine, amlodipine, andfelodipine) are more effective than non-DHP CCBs(eg, verapamil, diltiazem). Because CCBs have a greaterantihypertensive effect in the volume-expanded state,these drugs are particularly suitable for ESRD patients.

Importantly, the pharmacokinetics of CCBs are notaltered in ESRD, so the dosages do not require anymodi cation. In the United States Renal Data Systemdataset, the use of CCBs was associated with a lower riskof cardiovascular morbidity and mortality [40]. Becauseof their powerful antihypertensive properties and favor-able cardiovascular protection, CCBs are used widely inthe treatment of hypertension in dialysis patients. CCBs(either as monotherapy or as a component of combinationtherapy) are generally well tolerated by dialysis patients.DHP CCBs may cause tachycardia or headache, whichoften resolves with continued treatment. Unless there are


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no other available options, sublingual nifedipine shouldnot be used because of the risk of inducing precipitoushypotension. DHP CCBs can be safely given along withother classes of antihypertensive drugs, including β -blockers. Non-DHP CCBs may cause heart block anddecreased output in susceptible patients; they should beused with considerable caution, if at all, with β -block-

ers because of the potential for synergistic myocardialdepression. Non-DHP CCBs, however, are preferredover DHP CCBs in patients with supraventricular tachy-cardia, angina, or both.

β -Adrenergic blocking drugsβ -Blockers remain an important choice in the selectionof drugs for hypertension management, including drugsfor patients with ESRD. In the past, β -blockers werea popular component of triple drug therapy (vasodila-tor, β -blocker, and a diuretic) for hypertension in CKD.Because of their favorable outcomes in reducing cardio-vascular mortality and morbidity, β -blockers are usefulin the treatment of hypertension in patients with ESRD.Because of the high prevalence of coronary artery diseaseand congestive heart failure in the hemodialysis popula-tion, there is a sound rationale for the use of β -blockersin patients with ESRD. Renin suppression by β -blockersis another desirable pharmacologic property of immenseimportance in patients with CKD/ESRD. A number ofβ -blockers have pharmacologic properties (eg, lipid solu-bility, cardioselectivity) that make them a helpful choicefor hypertension treatment in CKD/ESRD. It is unusualfor β -blockers alone to control hypertension in hemodi-alysis patients, but they are often a necessary componentof multidrug therapy. In addition to the usual contraindi-cations, clinicians should consider possible adverse effectssuch as depression, erectile dysfunction, fatigue, and lipidor glucose abnormalities.

α -Adrenergic blocking drugsα -Blockers such as prazosin, terazosin, and doxazosinhave a diminishing role in the modern management ofhypertension; often, they are considered as “add-on”drugs. Because of the availability of better-tolerated andmore effective antihypertensive drugs, the use of α -block-ers has decreased substantially. There are no prospectiveoutcome studies with α -blockers in the CKD population,

and they offer no special advantages. In patients withresistant hypertension, if an α -blocker is used, effectssuch as postural hypotension should be monitored. Nodose adjustment is needed in patients with CKD/ESRD.

Dual inhibitors of α and β receptorsAdrenergic inhibition can be achieved with dua l inhibi-tors of α and β receptors, using drugs such as labetaloland carvedilol. These drugs have not been systemati-cally evaluated in patients with CKD/ESRD. Carvedilolhas been shown to have advantageous effects on glu-cose and lipid metabolism in hypertension, but it is

not known whether these ndings can be extended topatients with CKD/ESRD.

Centrally acting sympathetic agonistsThe central nervous system sympathetic agonists such asclonidine, guanabenz, and methyldopa are used less fre-quently in current treatment strategies for hypertension

control. They are not popular because of effects such asdry mouth, erectile dysfunction, fatigue, and reboundhypertension. Clonidine requires downward dose adjust-ment in patients with ESRD. Clonidine has been foundto be useful in treating restless legs syndrome in chronicdialysis patients. Like other sympathetic inhibiting drugs,clonidine is considered as an add-on (not a primary)option to treat hypertension in ESRD patients. Becauseof their high side-effect pro le, sympathetic inhibitors(reserpine, guanethidine) are rarely used to treat hyper-tension in the ESRD population.

Direct vasodilatorsDespite the advent of effective dialysis and modernantihypertensive drugs, some patients with ESRD havea therapeutic need for old direct vasodilators such ashydralazine and minoxidil to achieve their goal bloodpressure levels. Before the availability of RAS blockersand CCBs, direct vasodilators were used extensively inESRD to control hypertension: both hydralazine and min-oxidil, in conjunction with adequate volume control andβ -blockade, lowered the blood pressure signi cantly.

Because of brisk stimulation of re ex SNS activity,direct vasodilator therapy should be accompanied bysimultaneous β -blockade to offset tachycardia. To mini-mize adverse effects, the total daily dose of hydralazineshould not exceed 200 mg. For all practical purposes,minoxidil can be considered a more potent version ofhydralazine. It is a powerful vasodilator and is advo-cated for severe and resistant forms of hypertension. Theadverse-effect pro le of minoxidil is very similar to thatof hydralazine, with the addition of hair growth andmassive uid retention (managed by ultra ltration). Forthese reasons, the use of minoxidil is restricted. Despitethe complexities of using hydralazine and minoxidil, thesedrugs have a practical role in the management of resistanthypertension when they are used properly.

Secondary HypertensionSecondary forms of hypertension should be consideredin the dialysis patient with resistant hypertension, basedupon clinical and laboratory parameters. Althoughhypertension in patients with ESRD is generallyadvanced and linked to the decline in renal function, asecondary source (eg, renovascular or endocrine causesor sleep apnea) should be pursued on clinical groundsin selected patients. The extent of the workup should beguided by the clinical course, patient characteristics, andlaboratory ndings.


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Special Factors Affecting Blood Pressurein ESRDIt is believed that long (and slow) ultra ltration may con-trol hypertension more effectively in patients with ESRD.The mechanism by which prolonged dialysis is helpfulis not understood; it may be mediated by the removal ofvasoconstrictor substances. Simply achieving dry weight

may not suf ce for some patients on hemodialysis [41,42].Some studies also suggest that nocturnal dialysis mayimprove blood pressure control in hypertensive patientswith ESRD. Recent observations have indicated thathome blood pressure measurements may be highly use-ful in managing hypertension in hemodialysis patients,and out-of-clinic blood pressure levels should be con-sidered whenever possible in adjusting antihypertensivedrugs [43•]. This modality deserves to be applied morewidely in the hemodialysis population, not only in ESRDbut also for all patients with CKD. Out-of-of ce bloodpressure measurements are superior to those in the dialy-sis clinic, and it is also known that intradialytic bloodpressure recordings are more sensitive and valuable thanpredialytic/postdialytic blood pressure measurements inmanaging hypertension [44].

ConclusionsSystemic hypertension is extremely common in the ESRDpopulation, affecting a majority of patients undergoinghemodialysis or peritoneal dialysis. Uncontrolled hyper-tension is a signi cant factor in premature cardiovascularmorbidity and mortality in this high-risk group. A num-ber of hemodynamic and vasomotor mechanisms interactin an adverse fashion to cause and maintain hypertensionin ESRD. Unless blood pressure is properly controlled,ESRD patients are subject to various neurologic andcardiovascular complications. Management of hyperten-sion in the dialysis patient should take into considerationvariables such as lack of nocturnal fall in blood pressureas well as interdialytic and ambulatory measurements ofblood pressure levels. Aggressive control of hypertensionis essential to decrease the progression of ESRD [45••].Although there is a controversy about whether exces-sive blood pressure control produces poor outcomesin patients undergoing chronic ambulatory peritonealdialysis [46], no rigorously controlled clinical trials have

examined hypertension management in the dialysis popu-lation [47]. The points made in this article pertain mainlyto hemodialysis (the procedure used in the overwhelmingmajority of ESRD patients in the United States) ratherthan to peritoneal dialysis. In general, blood pressure con-trol in peritoneal dialysis patients is superior to those onhemodialysis. Hemodynamics in peritoneal dialysis aremore stable than in hemodialysis. The counter-regulatorymechanisms such as RAS and SNS are less likely to beactivated by peritoneal dialysis than by hemodialysis, andthe clearance characteristics of peritoneal dialysis are dis-tinctive and more physiologic than in hemodialysis.

Control of hypertension in the dialysis patient requiresproper and ef cient dialysis to maintain “dry weight”and aggressive application of antihypertensive drugs.Often multiple antihypertensive drugs are required. Theselection and dosages of these drugs depend on theirpharmacokinetics in ESRD and their dialyzability. Withjudicious control of ECF volume and antihypertensive

drugs, combined with supervised, tightly monitored bloodpressure measurements, we can improve blood pressurecontrol rates in ESRD and thereby reduce the overall dis-ease burden in this high-risk group of patients.

AcknowledgmentThe authors thank Ms. Nanci Hassell for her assistance inthe preparation of this manuscript.

DisclosureNo potential con icts of interest relevant to this articlewere reported.

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Paper 3 Management of Hypertension in DIALYSIS