supervised atenolol therapy in the management of hemodialysis hypertension

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Kidney International, Vol. 55 (1999), pp. 1528–1535 Supervised atenolol therapy in the management of hemodialysis hypertension RAJIV AGARWAL Division of Nephrology, Department of Medicine, Indiana University and RLR VA Medical Center, Indianapolis, Indiana, USA Supervised atenolol therapy in the management of hemodialy- hemodialysis patients and is held to be a standard of sis hypertension. adequacy of hemodialysis [1, 2, 4]. In the United States, Background. Uncontrolled hypertension continues to be a hypertension is present in as many as 72% of the patients common problem, particularly in noncompliant hemodialysis on chronic hemodialysis [5, 6]. Ambulatory blood pres- patients. Atenolol, a water soluble b-blocker has a prolonged sure (ABP) monitoring in treated hypertensive hemodi- half-life in renal failure and may serve as a useful antihyperten- sive agent in these patients. alysis patients demonstrates uncontrolled hypertension Methods. Hypertension was diagnosed by ambulatory blood in at least 50% of the interdialytic interval [7]. Further- pressure monitoring for 44 hours during an interdialytic interval more, there is also an absence of nocturnal decline in in eight chronic hemodialysis patients receiving no antihyper- blood pressure in these patients [7–10], which is the single tensive therapy. An average daytime blood pressure greater most important risk factor for development of left-ven- than 140/90 mm Hg or an average nighttime blood pressure greater than 120/80 mm Hg was used to define uncontrolled tricular hypertrophy [11]. The latter is an independent hypertension. Patients were then administered atenolol (25 predictor of morbidity and mortality in hemodialysis pa- mg) following hemodialysis three times a week. The efficacy of tients [2]. There is an urgent need for better treatment therapy was judged by ambulatory blood pressure monitoring of hypertension in chronic hemodialysis patients. three weeks after instituting atenolol therapy. Blood pressure Despite these adverse effects of hypertension in dial- loads above the threshold blood pressures during the day or ysis patients, surveys from nephrologists suggest that night were also calculated and compared before and after three weeks of atenolol therapy. they often do not treat mild to moderate hypertension Results. The mean 44-hour ambulatory blood pressure [12] because of the risk of intradialytic hypotension when (ABP) fell from 144 6 14/80 6 7 mm Hg to 127 6 13/69 6 antihypertensive drugs are used, in particular b-blockers 10 mm Hg (P , 0.001). The heart rate fell from 85 6 11 to [7]. Ironically, this may lead to a vicious cycle wherein 70 6 11 beats per minute. The systolic and diastolic blood uncontrolled hypertension leads to left-ventricular hy- pressure load was reduced from 71 6 25% and 30 6 24% to 35 6 26% and 11 6 17%, respectively (P , 0.001). There was pertrophy, which reduces ventricular compliance and a persistent antihypertensive effect over 44 hours. The blood precipitates further intradialytic hypotension [3]. In fact, pressure reduction was achieved without any increase in intra- experts suggest that the goal blood pressure in hyperten- dialytic symptomatic or asymptomatic hypotensive episodes, sive patients should be no different from what is recom- reduction in delivered dialysis, or statistically significant mended for the general population [13]. changes in serum potassium or glucose. We hypothesized that a water-soluble drug that is Conclusions. A supervised administration of atenolol fol- lowing hemodialysis effectively and safely controls hyperten- slowly metabolized and could be administered in the sion in chronic hemodialysis patients. This therapy can be par- hemodialysis unit three times per week may effectively ticularly valuable for noncompliant hemodialysis patients. control hypertension in hemodialysis patients. The ad- ministration of the drug in the dialysis unit would encour- age compliance, and removal of the drug by dialysis Hypertension greatly contributes to the high rates of would mitigate dialysis hypotension. Accordingly, we morbidity and mortality in hemodialysis patients [1–3]. tested the efficacy of atenolol, a kidney excreted A lower blood pressure is a good marker for survival in b-blocker that has a prolonged half-life in patients with end-stage renal disease. Key words: beta blocker, renal failure, antihypertensive agents, ateno- lol, blood pressure. METHODS Received for publication June 9, 1998 Subjects and in revised form October 5, 1998 Accepted for publication October 13, 1998 Patients between the ages of 18 and 80 years who had been on chronic hemodialysis for at least three months 1999 by the International Society of Nephrology 1528

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Page 1: Supervised atenolol therapy in the management of hemodialysis hypertension

Kidney International, Vol. 55 (1999), pp. 1528–1535

Supervised atenolol therapy in the management ofhemodialysis hypertension

RAJIV AGARWAL

Division of Nephrology, Department of Medicine, Indiana University and RLR VA Medical Center, Indianapolis, Indiana, USA

Supervised atenolol therapy in the management of hemodialy- hemodialysis patients and is held to be a standard ofsis hypertension. adequacy of hemodialysis [1, 2, 4]. In the United States,

Background. Uncontrolled hypertension continues to be a hypertension is present in as many as 72% of the patientscommon problem, particularly in noncompliant hemodialysison chronic hemodialysis [5, 6]. Ambulatory blood pres-patients. Atenolol, a water soluble b-blocker has a prolongedsure (ABP) monitoring in treated hypertensive hemodi-half-life in renal failure and may serve as a useful antihyperten-

sive agent in these patients. alysis patients demonstrates uncontrolled hypertensionMethods. Hypertension was diagnosed by ambulatory blood in at least 50% of the interdialytic interval [7]. Further-

pressure monitoring for 44 hours during an interdialytic interval more, there is also an absence of nocturnal decline inin eight chronic hemodialysis patients receiving no antihyper-

blood pressure in these patients [7–10], which is the singletensive therapy. An average daytime blood pressure greatermost important risk factor for development of left-ven-than 140/90 mm Hg or an average nighttime blood pressure

greater than 120/80 mm Hg was used to define uncontrolled tricular hypertrophy [11]. The latter is an independenthypertension. Patients were then administered atenolol (25 predictor of morbidity and mortality in hemodialysis pa-mg) following hemodialysis three times a week. The efficacy of tients [2]. There is an urgent need for better treatmenttherapy was judged by ambulatory blood pressure monitoring of hypertension in chronic hemodialysis patients.three weeks after instituting atenolol therapy. Blood pressure

Despite these adverse effects of hypertension in dial-loads above the threshold blood pressures during the day orysis patients, surveys from nephrologists suggest thatnight were also calculated and compared before and after three

weeks of atenolol therapy. they often do not treat mild to moderate hypertensionResults. The mean 44-hour ambulatory blood pressure [12] because of the risk of intradialytic hypotension when

(ABP) fell from 144 6 14/80 6 7 mm Hg to 127 6 13/69 6 antihypertensive drugs are used, in particular b-blockers10 mm Hg (P , 0.001). The heart rate fell from 85 6 11 to[7]. Ironically, this may lead to a vicious cycle wherein70 6 11 beats per minute. The systolic and diastolic blooduncontrolled hypertension leads to left-ventricular hy-pressure load was reduced from 71 6 25% and 30 6 24% to

35 6 26% and 11 6 17%, respectively (P , 0.001). There was pertrophy, which reduces ventricular compliance anda persistent antihypertensive effect over 44 hours. The blood precipitates further intradialytic hypotension [3]. In fact,pressure reduction was achieved without any increase in intra- experts suggest that the goal blood pressure in hyperten-dialytic symptomatic or asymptomatic hypotensive episodes,

sive patients should be no different from what is recom-reduction in delivered dialysis, or statistically significantmended for the general population [13].changes in serum potassium or glucose.

We hypothesized that a water-soluble drug that isConclusions. A supervised administration of atenolol fol-lowing hemodialysis effectively and safely controls hyperten- slowly metabolized and could be administered in thesion in chronic hemodialysis patients. This therapy can be par- hemodialysis unit three times per week may effectivelyticularly valuable for noncompliant hemodialysis patients. control hypertension in hemodialysis patients. The ad-

ministration of the drug in the dialysis unit would encour-age compliance, and removal of the drug by dialysis

Hypertension greatly contributes to the high rates of would mitigate dialysis hypotension. Accordingly, wemorbidity and mortality in hemodialysis patients [1–3]. tested the efficacy of atenolol, a kidney excretedA lower blood pressure is a good marker for survival in b-blocker that has a prolonged half-life in patients with

end-stage renal disease.Key words: beta blocker, renal failure, antihypertensive agents, ateno-lol, blood pressure.

METHODSReceived for publication June 9, 1998 Subjectsand in revised form October 5, 1998Accepted for publication October 13, 1998 Patients between the ages of 18 and 80 years who had

been on chronic hemodialysis for at least three months 1999 by the International Society of Nephrology

1528

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Agarwal: Atenolol in hemodialysis hypertension 1529

Table 1. Demographic characteristics of the study population Drug titrationAge years 52617 Patients initially received a 25 mg dose postdialysisNumber male 4 of 8 three times a week administered by a nurse for one week,Predialysis weight kg 90.0631.8

and the dose was titrated at weekly intervals to adjustPost-dialysis weight kg 86.2630.9Duration on hemodialysis months 72 (32–270) the postdialysis blood pressure to 140/90 mm Hg or lessErythropoeitin dose U/week median 8000 (0 to 30,000) to a maximum dose of 100 mg atenolol. The resting heartHematocrit vol % 33.364.0

rate of less than 60 beats per minute or the predialysisPre-hemodialysis BP mm Hg 152615/82612Post-hemodialysis BP mm Hg 134616/73610 blood pressure of less than 110 mm Hg systolic wasLeft ventricular diastolic posterior wall used to reduce the dose of atenolol. Forty four-hour

thickness cm 1.2360.10ambulatory blood pressure measurement (ABPM) was

All data are means and standard deviation. Medians and ranges are expressed repeated after three weeks of therapy with atenolol onfor duration of hemodialysis and erythropoeitin dose.either the first or second dialysis of the week. Dry weight,dialysis prescription, and the dose of erythropoietin werenot modified for the duration of the study.

and were not on antihypertensive therapy were eligibleLaboratory and clinical monitoringfor the study. Sitting blood pressures in the hemodialysis

Casual blood pressures and heart rates were moni-unit were recorded in the hemodialysis unit before andtored in the dialysis unit before and after dialysis byafter dialysis for two weeks. Patients with an averagethe dialysis nurse using an automated blood pressure-postdialysis blood pressure of over 200/110 mm Hg weremeasuring device with the patient seated. The frequencyexcluded. Other exclusion criteria were patients withof symptomatic hypotensive episodes, defined as systolicsevere heart failure, bradycardia, predialysis potassiumblood pressure of 90 mm Hg or less, requiring treatmentof more than 5.9 mEq/liter in the previous two months,with saline and/or associated with cramps, nausea, ordiabetes mellitus requiring insulin, allergy to atenolol,dizziness, was recorded during the nine hemodialysisor previous adverse effect to b-blockers. All patientstreatments prior to starting atenolol and for the ninewere dialyzed three times per week between 3.5 and 5hemodialysis treatments during atenolol therapy. Serum

hours with a bicarbonate dialysate (35 mEq/liter), 140 chemistries and complete blood counts were obtained,mEq/liter Na and 1 to 3 mEq K. Dry weight was defined and the amount of dialysis (Kt/V, Daugirdas second gen-as a lack of edema or physical signs of volume overload eration formula using an equilibrated postdialysis bloodand cramping, nausea, or vomiting with a fall in systolic urea nitrogen) was calculated before and after atenololblood pressure to less than 90 mm Hg on challenging therapy.weight by more than 0.5 kg per dialysis session. The

Statistics and power analysisstudy was approved by the Institutional Review Board,and all patients gave written informed consent. Blood pressures were averaged into daytime blood

pressure (6 p.m. to 10 p.m.) and nocturnal blood pressureDiagnosis of hypertension and 44-hour ambulatory (10 p.m. to 6 p.m.). A paired t-test was used to compareblood pressure monitoring average ambulatory blood pressures, daytime blood

pressures, nocturnal blood pressures, and blood pressureAmbulatory blood pressures were recorded every 20loads before and after atenolol as described by othersminutes during the day (6 a.m. to 10 p.m.) and every 30[14]. The frequency of hypotensive episodes over nineminutes during the night (10 p.m. to 6 a.m.) using adialysis during atenolol therapy was compared with base-Spacelab 90207 ABP monitor (SpaceLabs Medical Inc.,line nine dialysis prior to starting atenolol using YatesRedmond, WA, USA). Recordings began immediatelycorrected chi-square test. Casual blood pressure re-after hemodialysis and terminated immediately beforecordings in the hemodialysis unit during atenolol therapythe prior dialysis. Ambulatory blood pressures werewere compared with baseline using multivariate re-never recorded over the weekend. Data were analyzedpeated-measures analysis of variance. Data were ana-

using ABP Report Management System software, ver- lyzed separately for first dialysis of the week and mid-sion 1.03.05 (SpaceLabs Medical Inc.). Ambulatory week dialysis. Baseline blood pressures before and afterblood pressure and heart rates were averaged over the hemodialysis (week 0) were compared with blood pres-entire course of recording, as well as separately during sures during the ensuing three weeks (weeks 1, 2, and 3)the day and during night. Blood pressure thresholds were using three-way repeated-measures analysis of variance140/90 mm Hg during the day and 120/80 mm Hg during within weeks (four levels), predialysis and postdialysisthe night; that is, average recordings over these levels blood pressure (two levels), and systolic and diastolicwere classified as hypertension. Blood pressure loads blood pressures (two levels). A two-way repeated-mea-were calculated as a percentage of recordings above sures analysis of variance was performed within weeks

(four levels) and predialysis and postdialysis heart ratesthreshold limits during the 44-hour period.

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Agarwal: Atenolol in hemodialysis hypertension1530

Table 2. Ambulatory interdialytic blood pressures

Baseline Atenolol

Systolic Diastolic Heart Systolic Diastolic HeartBP BP Rate BP BP Rate

Average ABP 144 614 80 67 85 611 127613 69 610 70 611Average BP load 71 625 30 624 35 626 12 619Daytime ABP 146 613 83 68 87 611 127613 70 611 69 611Daytime BP load 65 630 26 626 26 627 11 617Night ABP 146 616 77 68 83 611 128616 66 610 71 612Night BP load 84 622 38 629 62 633 17 627

All data are means and standard deviation. All atenolol data are significantly different from baseline (P , 0.05) except nocturnal BP load.

Fig. 1. Mean ambulatory blood pressure re-cordings and heart rates at baseline (d) andafter three weeks (j) of atenolol therapy. Theerror bars represent the standard error of themean. The shaded columns represent nights(10 p.m. to 6 p.m.).

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Agarwal: Atenolol in hemodialysis hypertension 1531

Fig. 2. Systolic and diastolic ambulatoryblood pressure recordings at baseline (d) andafter three weeks (j) of atenolol therapy. Theerror bars represent the standard error of themean. The shaded columns represent nights(10 p.m. to 6 p.m.).

(two levels). All statistical analyses were carried out us- disease. Seven of the eight patients were African Ameri-cans. Demographic characteristics and results of 44-houring standard procedures on Statistica for Windows, re-ABPM are shown in Tables 1 and 2, respectively. Alllease 4.5 (StatSoft, Inc., Tulsa, OK, USA). Using eightpatients had left-ventricular hypertrophy by echocardio-patients, the study had 80% power at 0.05 significancegram. In five patients, the lowest dose of atenolol (25level to detect a 12 mm Hg change in blood pressuremg) three times per week administered postdialysis waswhen the standard deviation of the differences was assufficient to reduce the blood pressure to goal level. Twolarge as 10 mm Hg.patients required 50 mg three times per week, and onepatient required 100 mg three times per week atenolol.

RESULTS Mean (6 sem) 44-hour interdialytic ABP and heart ratesThree patients had glomerulonephritis, and the re- are shown in Figure 1. Atenolol reduced the overall 44-

hour interdialytic blood pressure by 16.9 mm Hg systolicmaining had hypertension as the cause of end-stage renal

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Agarwal: Atenolol in hemodialysis hypertension1532

Fig. 3. Effect of atenolol on blood pressuresrecorded in the hemodialysis unit. Open sym-bols are predialysis blood pressures, and closedsymbols postdialysis blood pressures. Squaresand triangles are systolic and diastolic pres-sures, respectively. Each patient had bloodpressures recorded for nine dialysis over athree-week period before initiating atenololand nine dialysis during atenolol therapy.There was a significant effect of atenolol onblood pressures.

Table 3. Serum chemistries, hematocrit and Kt/V mm Hg). The 44-hour interdialytic mean (6 sem) ABPwith atenolol therapy

and heart rates are shown in Figure 1. Systolic and dia-Baseline Atenolol stolic ABPs before and after three weeks of atenolol are

Hemoglobin g/dl 10.9561.17 11.1461.14 shown in Figure 2.Hematocrit vol % 33.5463.86 33.7363.68 We compared blood pressures recorded in the hemo-Na mEq/liter 13961.6 13962.5K mEq/liter 4.8860.53 4.4060.48 dialysis before and after dialysis during the three weeksCl mEq/liter 9964.9 9763.9 prior to atenolol with those during the three weeks dur-CO2 mEq/liter 21.863.0 22.963.4

ing atenolol therapy (Fig. 3). Thus, each patient servedBUN mg/dl 71.8617.6 68.5614.9Cr mg/dl 14.364.0 13.663.5 as his or her own control. The average blood pressureGlucose mg/dl 99637 125668

before dialysis prior to atenolol therapy was 153/85 mmCalcium mg/dl 9.360.8 9.461.4Phosphorus mg/dl 4.6561.52 5.3461.66 Hg, which fell to 139/75 mm Hg during therapy. BloodKt/V 1.5960.33 1.5560.44 pressures recorded after dialysis fell from 137/77 mm HgPredialysis weight 90.1632.1 90.1632.1

to 127/71 mm Hg. Using a four-way multivariate analysisPostdialysis weight 86.1630.9 86.3631.1

of variance, the effect of atenolol was highly significantAll data are means and standard deviation. No statistical difference was pres-ent before or after atenolol therapy. (P 5 0.0018).

The frequency of symptomatic or asymptomatic hypo-tensive episodes was not increased by atenolol. Threedialysis treatments, one each in three patients, were com-and 11.6 mm Hg diastolic blood pressure. The heartplicated by symptomatic hypotension prior to atenololrate was reduced by 15.5 beats per minute. The bloodtherapy. After atenolol, three treatments were compli-pressure load, that is the percentage of recordings overcated by symptomatic hypotension. One of 72 dialysis140/90 mm Hg during the day or over 120/80 at night,treatments was complicated by asymptomatic hypoten-was reduced 36% and 18%, systolic and diastolic, respec-sion prior to atenolol and 4 of 72 dialysis treatmentstively. The reduction in daytime ABP was more remark-

able (18.8/12.6 mm Hg) than nighttime ABP (13.8/10.5 after starting therapy (Yates corrected chi-square, P 5

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Agarwal: Atenolol in hemodialysis hypertension 1533

Table 4. Results of ANOVA on heart rate

First dialysis of the week Midweek dialysis

Mean square Mean square Mean square Mean squareeffect error P level effect error P level

Weeks (4) 953.0 138.0 0.002 1312.8 120.9 0.0002Pre- or post-dialysis heart rate (2) 151.6 44.0 0.10 39.1 32.5 0.309Weeks 3 HR (2) 28.9 43.5 0.58 35.8 47.1 0.529

Heart rates measured before and after dialysis analyzed by repeated measures 2 way ANOVA. The two variables were time (4 weeks: one week prior to atenololand three weeks during atenolol therapy) and dialysis (either pre-dialysis or post-dialysis).

Fig. 4. Casual blood pressure and heart ratesduring the first dialysis of the week (A) andmidweek dialysis (B). The open symbols rep-resent prehemodialysis parameters, and closedsymbols are posthemodialysis parameters. Theweeks on the abscissa reflect the number ofweeks on atenolol therapy; zero week is thebaseline. There was a significant fall in heartrates for both first and midweek dialysis. How-ever, a significant fall in blood pressure wasseen for only the midweek dialysis (see textfor details).

0.39). Serum chemistries, hematocrit, and Kt/V are shown DISCUSSIONin Table 3 and were uninfluenced by atenolol therapy. The major finding in this study was that nurse-adminis-

There was a significant lowering of heart rate (Table tered, three-times-per-week atenolol therapy effectively4 and Fig. 4A) with atenolol on first dialysis of the week, controlled hypertension in patients on hemodialysis oncebut there was no significant effect on blood pressure dry weight was achieved. The effect of the drug on blood(Table 5 and Fig. 4A). When similar analysis was re- pressure was present for at least 44 hours, as assessedpeated for the midweek dialysis, a significant lowering by ambulatory blood pressure monitoring. The drug re-of heart rates (Table 4 and Fig. 4B), as well as blood duced the overall systolic blood pressure load over 44

hours by more than 50% and diastolic blood pressurepressures (Table 5 and Fig. 4B), was seen.

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Agarwal: Atenolol in hemodialysis hypertension1534

Table 5. Results of ANOVA on first and mid-week hemodialysis blood pressures

First dialysis of the week Midweek dialysis

Mean square Mean square Mean square Mean squareeffect error P level effect error P level

Weeks (4) 344.6 192.0 0.18 831.8 193.1 0.02Pre or post-dialysis (2) 6223.1 789.8 0.03 2592 699.4 0.10Systolic or diastolic BP (2) 134,453.5 812.6 ,0.001 118,098.0 1030.2 ,0.001Weeks 3 dialysis 57.0 282.9 0.89 150.8 154.5 0.42Weeks 3 BP 117.1 57.7 0.14 74.5 131.1 0.64Dialysis 3 BP 1060.9 161.4 0.04 903.1 124.8 0.03Weeks 3 dialysis 3 BP 36.1 66.4 0.65 7.6 41.9 0.90

Blood pressures measured in the dialysis unit analyzed by repeated measures 3 way ANOVA. The three variables were time (4 weeks: one week prior to atenololand three weeks during atenolol therapy), dialysis (2 levels: either pre-dialysis or post-dialysis), and blood pressure (2 levels: systolic or diastolic). Data for firstdialysis of the week and mid-week dialysis are shown to contrast the effect of time on BP. There is a significant fall in BP over the weeks of atenolol only for themidweek dialysis, but not for the first dialysis of the week. There is a significant interaction term (Dialysis 3 BP), which is indicative of greater fall in systolic BPwith dialysis.

load by 66%. The antihypertensive effect of atenolol was nificantly slower when compared with baseline (Fig. 4A).The data can be interpreted to mean that the antihyper-not complicated by an increase in frequency of dialysis

hypotension, hyperkalemia, hyperglycemia, or lower tensive effect of atenolol wanes off by 72 hours. In otherwords, despite the b-blockade, volume expansion over-amount of delivered dialysis. The half-life of atenolol

during dialysis is 7.5 6 3.7 hours [15], and the rapid whelms the antihypertensive activity of atenolol. Alter-natively, casual blood pressure recordings may be insen-dialyzability of atenolol may account for the lack of dial-

ysis hypotension in our patients. sitive to detect a true antihypertensive effect of atenolol;if 72-hour ABP monitoring were performed, a small anti-Casual prehemodialysis blood pressures in the dialysis

unit were mildly elevated. However, all patients had hy- hypertensive effect may have been seen. Whether anadditional dose of atenolol over the weekend would con-pertension by ambulatory blood pressure monitoring, and

all had left-ventricular hypertrophy by echocardiogram. fer additional antihypertensive benefit cannot be an-swered by this study. Another cautionary note is in order.Therefore, treatment with an antihypertensive agent was

justified. The median duration of dialysis in our patients was sixyears, and none had measurable residual renal function.Our findings are in agreement with what is known

about the pharmacokinetics and pharmacodynamics of Because kidneys are the major route of removal of ateno-lol, patients with substantial residual renal function mayatenolol. In normal individuals, 50% of an oral dose is

absorbed, and peak plasma levels occur in two to four need more frequent dosing compared with our patients.This study is in agreement with other uncontrolledhours after oral ingestion [16]. The half-life is five to six

hours, the excretion being almost exclusively renal, and observations that suggest that b-blockers are effectivein controlling blood pressure. For example, De Fremontmetabolism is minimal [16]. The bioavailability of the

drug is not different in patients with renal failure [17], but et al found the mean arterial pressure to fall from 112 617 mm Hg postdialysis to 100 6 4 mm Hg postdialysisthe half-life in patients with renal failure is significantly

prolonged [15, 17, 18]. There is good correlation between after metoprolol therapy [20]. Maggiore et al noted arise in blood pressure after stopping propranolol in eightthe peak concentration of atenolol and the peak pharma-

codynamic response, as measured by a reduction in exer- hemodialysis patients [21]. Both metoprolol and pro-pranolol have extensive hepatic metabolism, and somecise heart rate and systolic blood pressure [19]. The low-

ering of heart rate and blood pressure even after a 25 of the metabolites can accumulate in renal failure pa-tients [18]. In contrast to these uncontrolled observa-mg dose of atenolol suggests good bioavailability, and

the predicted peak level of the drug corresponds to the tions, our controlled study convincingly demonstratesthe utility of atenolol in reducing blood pressure. Thenadir of blood pressure seen in our patients (Fig. 1). Our

study confirms the suggestion of Kirch et al: A dose of control of hypertension in these patients does not comeat an expense of poor dialysis or intradialytic hypoten-50 mg atenolol given postdialysis may be adequate to

control hypertension in hemodialysis patients [17]. sion. However, the drop in predialysis blood pressurereduces the margin of error in estimating dry weightWe did not monitor ABP over 72 hours in our patients.

When casual blood pressure recordings in the dialysis and ultrafiltration rate with regard to blood pressure.Furthermore, a deliberate reduction in dry weight byunit during the first dialysis of the week were compared

at baseline and after instituting atenolol therapy, no sta- trial and error may suffice to achieve a normal bloodpressure without the need for any antihypertensive medi-tistically significant difference was seen (Fig. 4A). This

is despite the fact that heart rate after atenolol was sig- cation [22]. In patients who nevertheless need antihyper-

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Agarwal: Atenolol in hemodialysis hypertension 1535

JP, de Leuw PW, Leunissen KML: Diurnal blood-pressure varia-tensive therapy, three-times-a-week dosing with atenololtions in haemodialysis and CAPD patients. Nephrol Dial Trans-

could enhance compliance and can be administered by plant 9:1616–1621, 199410. Baumgart P, Walger P, Gemen S, Von Eiff M, Raidt H, Rahnthe hemodialysis nurse. Additionally, b-blockade can pro-

KH: Blood pressure elevation during the night in chronic renalvide secondary prophylaxis of coronary artery disease infailure, hemodialysis and after renal transplantation. Nephron

these patients. 57:293–298, 199111. Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C, Benemio

G, Boldrini F, Porcellati C: Circadian blood pressure changesACKNOWLEDGMENTS and left ventricular hypertrophy in essential hypertension. Circula-tion 81:528–536, 1990This work was supported in part by a grant from the American Heart

12. Ritz E, Koch M: Morbidity and mortality due to hypertension inAssociation, Indiana Affiliate #INN-97-200-BGIAR to the author. Thepatients with renal failure. Am J Kidney Dis 21(Suppl 2):113–118,nursing assistance of Ms. Patricia M. Olin, R.N., and the helpful com-1993ments by Dr. James A. Hasbargen are gratefully acknowledged.

13. Ritz E: Hypertension and cardiac death in dialysis patients: Shouldtarget blood pressure be lowered? Semin Dial 6:227–228, 1993Reprint requests to Rajiv Agarwal, M.D., Division of Nephrology,

14. Neutel JM, Smith DHG, Ram CVS, Kaplan NM, PapademetriouDepartment of Medicine, Indiana University and RLR VA MedicalV, Fagan TC, Lefkowitz MP, Kazempour MK, Weber MA: Appli-Center, 1481 West 10th Street, 111N, Indianapolis, Indiana, 46202 USA.cation of ambulatory blood pressure monitoring in differentiatingE-mail: [email protected] antihypertensive agents. Am J Med 94:181–187, 1993

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