Ambulatory blood pressure monitoring is a useful clinical tool in nephrology

me oha

National

lournal of the

Kidney

Foundation

AJKD

Amriean Journal ofKidney DiseasesVOL 30, NO 5, NOVEMBER

EDITORIAL

1997

REVIEW

Ambulatory Blood Pressure Monitoring Is a Useful Clinical Tool in Nephrology George A. Mansoor,

MD, and William 6. White, MD

0 Hypertension is a key factor in the genesis and deterioration of many renal diseases and is also a risk factor for death in patients with end-stage renal disease. However, the standard methods of measurement are prone to variability, especially in patients undergoing dialysis. The technique of ambulatory blood pressure monitoring allows a better assessment of overall blood pressure levels and promises to assume a bigger role in the care of renal patients. Ambulatory blood pressure monitoring is widely used in hypertension trials, and the reports of several consensus meetings on the clinical uses of ambulatory blood pressure monitoring have been published. Two similar validation protocols now exist for ambulatory blood pressure monitors, and tables of populationbased normal blood pressures for age and gender are available. The available evidence suggests that ambulatory blood pressure compared with blood pressure measured in the physician’s office is better correlated to left ventricular mass in subjects with chronic renal disease. Furthermore, studies in subjects with chronic renal disease and those undergoing renal replacement therapy show that blood pressure control is suboptimal in many patients and that nocturnal blood pressure is generally higher than in control subjects. Further insights into overall blood pressure behavior in this population will certainly emerge in the future. 0 1997 by the National Kidney Foundation, Inc. INDEX WORDS: renal disease;

Blood circadian.

pressure;

ambulatory

blood

pressure;

0

VER THE PAST 15 years, much has been learned about ambulatory blood pressure, and several consensus groups’-3 have recommended ambulatory blood pressure monitoring in the care of selected patients. The Fifth Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure’ indicated that ambulatory blood pressure monitoring “is a unique tool for extended assessment of particular hypertensive patients with special clinical problems.” The document cautioned that ambulatory blood pressure monitoring is unnecessary for the diagnosis and management of the majority of hypertensive patients. Likewise, the American College of Cardiology Hypertensive Diseases Committee’ considered the technique “a mature, clinically applicable technology” and stated that ‘ ‘appropriately constrained ambulatory blood pressure monitoring can be highly

American

Journal

of Kidney

Diseases,

Vol 30, No 5 (November),

blood

pressure

measurement;

renal

insufficiency;

cost-effective.” There therefore is some consensus on the clinical indications for ambulatory blood pressure monitoring. Levels of ambulatory blood pressure in the general population are now available, and operational thresholds for defining hypertension have been proposed.4 Furthermore, progress also has been made regarding methods of device validation, and criteria have been published in both the United States and Europe.5-7 Ambulatory blood pressure monitoring continues From the Section of Hypertension and Vascular Diseases, University of Connecticut Health Center, Farmington, CT. Received April 21, 1997: accepted in revised form July 8, 1997. Address reprint requests to George A. Mansoor, MD, Section of Hypertension, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3940. 0 1997 by the National Kidney Foundation, Inc. 0272-6386/97/3005-0002$3,00/O

1997:

pp 591-605

591

MANSOOR

to be widely used in clinical hypertension trials.* The method has become a mature and useful technique in clinical medicine. In the area of clinical nephrology, ambulatory blood pressure monitoring has the potential to improve the understanding of the role of blood pressure variability in the progression of renal disease and to aid in the diagnosis and treatment of hypertension in patients with chronic renal insufficiency and those requiring renal replacement therapy. At present, there is no consensus on the role of ambulatory blood pressure monitoring in the care of patients with renal disease. However, a small body of data has emerged on the utility of ambulatory blood pressure monitoring in clinical nephrology practice. The aim of this report is to review the ambulatory blood pressure measurement methodology and the clinical uses of ambulatory blood pressure monitoring, and to summarize its current applications in clinical nephrology. DEVICES

AND PRACTICAL

ISSUES

Ambulatory blood pressure monitors use a variety of techniques and algorithms, including auscultation, oscillometry, R-wave-gated auscultation, and combined oscillometry-auscultation, to determine blood pressure. A standard compact unit along with analytical software costs approximately $3,000 to $5,000 in initial acquisition cost (excluding the computer). The devices allow the user to program the frequency of blood pressure readings, rate of inflation and deflation, maximum inflation pressure, and criteria for repeat measurements. For optimal results, the patient should be instructed adequately about the care of the monitor during the study period (Table 1). Because arm motion can lead to substantial errors, during each individual blood pressure measurement, the patient should hold the arm motionless and relaxed.’ At initial attachment and at the time of removal of the monitor, it is imperative that the ambulatory blood pressure monitor agree with the mercury sphygmomanometer to within 5 mm Hg. The blood pressure and heart rate data are downloaded into customized software and edited, and summary statistics and graphic displays are generated. Ambulatory blood pressure monitoring studies

Table

1. Practical Pressure

Issues Monitoring

AND

WHITE

in Blood

Instruct the patient adequately about the aims of the study Instruct the patient in the use of the patient-activated button Tell patients to avoid water and not to remove monitor Tell patients to avoid intense exercise during the study period Instruct patients to hold arm motionless during actual readings Avoid placing the cuff too low on elbow Ensure that monitor is within %!5 mm Hg of mercury sphygmomanometer before and at the end of the study Give patient a contact person for any problems during the study Instruct patient to call if they develop any pain or discoloration of the skin distal to the cuff

are generally performed for 24 hours, although in some patients shorter” or longer study periods (patients for whom 1 day of monitoring may not adequately represent overall blood pressure) may be appropriate. The optimal timing for hook-up and duration of ambulatory blood pressure studies in patients undergoing hemodialysis is not unclear. The blood pressure of hemodialysis or peritoneal dialysis patients is more likely to be adequately represented by 48-hour studies than 24-hour studies because of the inherent variability of blood pressure in this group. Ambulatory blood pressure studies also should be performed on work days rather than off days, since blood pressure on work days tends to be higher than blood pressure taken at home.” Patients also should be asked to keep a diary of relevant physical and mental activities, times of going to bed, times of medication intake and meals, and any symptoms that may be clinically important (eg, dizziness or headache). Many blood pressure monitors have an event button that patients can activate to start a reading if they are experiencing symptoms. In a few centers, simultaneous electronic activity monitoring is performed during the ambulatory blood pressure study. Such activity data may be used for analyzing the relationship of activity to the patients’ blood pressure or in the determination of sleep times. However, activity monitoring is a research tool ,and is not

AMBULATORY

04 0

BP MONITORING

IN RENAL

u t

300600

DISEASE

systolicBP diastolic BP

I 900 12@0 1500 1800 2100 2400 Time of Day

Fig 1. A typical blood pressure profile obtained from a hypertensive subject. Asleep blood pressure is clearly lower than awake blood pressure. Note the early morning increase in blood pressure.

indicated in the routine application of ambulatory blood pressure monitoring. Ambulatory blood pressure monitors perform less reliably in patients with atria1 fibrillation or frequent premature ventricular beats,‘* and also in patients with very obese or tapering arms. Although some patients report that it is inconvenient and interferes with sleep and planned activities,13 the technique is safe and adverse effects are minimal. Ambulatory blood pressure monitors should never be placed on an arm with a functional arteriovenous fistula because of the risk of thrombosis. DATA ANALYSIS AND REPORTING OF RESULTS

The typical blood pressure study provides from 60 to over 100 readings in the 24-hour period, depending on the frequency of measurement (Fig 1). More readings usually are taken during the awake period (four to six readings per hour) than during the sleep period (one to three readings per hour). However, before any analysis is performed on the raw data, editing is usually necessary. This process should be minimized and should exclude only physiologically impossible readings to avoid introducing bias into the data. l4 Several types of descriptive statistics can be easily calculated from the data obtained,‘4*‘5 with average levels of 24-hour, daytime (awake), nighttime (asleep), and work blood pressure being the most common. The use of the &hour time blocks for analysis as done in some centers

593

allows correlation of blood pressure and heart rate changes to work hours (8 AM to 4 PM), evening hours (after work), and sleeping hours. These averages are simple to compute, are known to correlate with hypertensive left ventricular hypertrophy, and also can provide an estimate of variability for the period by the amount of data dispersion. They also are easy to compare with suggested averages of normality for ambulatory blood pressure. Despite the ease of use, summary averages tend to hide peak and trough levels of blood pressure that may have clinical value, especially in the patient who has symptoms of hypotension or episodic hypertension. Blood pressure changes around the early morning waking period are of particular interest to researchers and clinicians because an excess of cardiovascular events has been observed around this time periodr6 (Fig 1). Another type of index used in ambulatory blood pressure data analysis is the blood pressure load.15 This is defined as the percentage of blood pressure readings elevated during the period of interest. The blood pressure load may be calculated for 24 hours and for awake and asleep periods. Thresholds that are used by our group for this calculation are 140/90 mm Hg during the awake period and 120/80 mm Hg during the asleep period, although some centers use 140/90 mm Hg for the entire period. Although normotensive subjects may display occasional elevated blood pressure readings, the blood pressure load for the 24-hour period is usually less than 10%. At blood pressure loads of approximately 40% to 50%, a significant proportion of patients will show echocardiographic evidence of left ventricular hypertrophy; hence, blood pressure load is also pathophysiologically relevant as an analytic method. The blood pressure load is limited by ceiling values (100%) in moderate to severely hypertensive patients and hence will not discriminate between subjects with higher levels of blood pressure. Other methods of data analysis have been developed, including area under the curve and cusums and cosinor analyses, but they are more difficult to calculate and are not used much clinically. The 24-hour data for each patient are traditionally separated into awake or daytime and asleep or nighttime periods, and then separate averages

MANSOOR

594

and “dipping” status are determined. The “dipping” status refers to whether the observed change in blood pressure during sleep compared with the awake period is normal (decline by approximately 10% to 15%) reduced (< lo%), or exaggerated. Many different methods have been used to separate daytime (awake) and nighttime (asleep) periods. These methods include fixed separation of the data using set “sleep” hours (eg, 7 AM to 10 PM is daytime, 10 PM to 7 AM is nighttime), using actual patient reported sleep times, using short fixed-clock time intervals (eg, 10 AM to 6 PM is awake time and 12 AM to 5 AM is asleep time), or using simultaneous actigraphic data. “-I9 Awake and sleep periods should be analyzed separately because accepted normal ranges for blood pressure are different for these two physiologically different periods. Sleep is associated with a reduction in blood pressure and heart rate in most normotensive and hypertensive subjects. Blood pressure and heart rate also decrease if patients sleep during the daytime,” and some account needs to be taken of these siesta periods in the analysis. Despite this separation into day and night, the overall blood pressure exposure is probably important in determining hypertensive complications. The nocturnal decrease in blood pressure (socalled dipper v nondipper status) has some pathophysiologic significance21 and is also calculated. A nondipper status has been associated with left ventricular hypertrophy,22 excessive stroke,23 and an increase in cardiovascular events in women.24 There is no agreement on the best methods to determine the patients’ dipping status. The awake-asleep difference in blood pressure can be expressed as a percentage of awake blood pressure, as an absolute decline (in mm Hg), or as a ratio of asleep to awake blood pressure.25 Normotensive subjects generally have a 10% to 15% lower blood pressure during the asleep period compared with the awake period. Factors that may influence the extent of sleep blood pressure decline include age, the presence of secondary hypertension, and level of physical activity.26 The definition of dipper versus nondipper status is highly variable among investigators, although use of the actual patient sleep times improves the definition.” For practical purposes, the patient who has a less than 10% reduction in mean arte-

Table

2. Contents Blood

of the Typical Pressure Report

AND

WHITE

Ambulatory

Patient demographics Medications at the time of the study and times of intake Date and time of study and patient sleep and meal times Date and time of any symptoms and quality of sleep during the study Number of attempted readings/number and percentage of actual readings used in the analysis Blood pressure and heart rate at the time of hookup Average 24-hour, awake, and asleep blood pressures and heart rates Blood pressure load for 24-hour, awake, and asleep periods Recommendations based on the overall findings Graphic display of blood pressure and heart rate over the study period

rial pressure during sleep may be considered a nondipper. The typical ambulatory blood pressure report (Table 2) will contain demographic data on the patient, average blood pressure and blood pressure loads for the periods of interest, and advice regarding further management. NORMOTENSION AS DEFINED BY AMBULATORY BLOOD PRESSURE

There are now substantial data regarding normal 24-hour blood pressure profiles in adults, adolescents, and pregnant women.27 In adults, several population studies have found similar ranges of ambulatory blood pressure levels among normotensive subjects. In the three largest studies of normotensive subjects,27 the 95th percentiles are remarkably similar. Staessen et al4 have suggested operational definitions for ambulatory blood pressure (Table 3) that are based on this large body of epidemiologic data. While ageand gender-based tables are also available, the thresholds are easy to use on a day-to-day basis. COMPARATIVE RELEVANCE OF OFFICE AMBULATORY BLOOD PRESSURE TO VASCULAR DISEASE

AND

Since large epidemiologic and clinical studies have already shown that blood pressure that is elevated when measured in the physician’s office is a risk factor for future cardiovascular events,

AMBULATORY

BP Table

MONITORING

IN RENAL

3. Ambulatory

Blood

DISEASE

Pressure

595

Levels

in Normotensive

Normotension Daytime* blood pressure (mm Hg) Nighttime* blood pressure (mm Hg) 24-Hour blood pressure (mm Hg) * Definitions Reproduced

not explicitly by pekmission

stated, and of Oxford

it could be argued that office readings should be used for all decision making. However, it appears that ambulatory blood pressure levels, compared with office blood pressure levels, are more closely related to hypertensive organ damage, especially left ventricular hypertrophy.28,29 These data, however, have been criticized because the relationship of blood pressure to hypertensive organ injury has been studied mainly in cross-sectional designs. Furthermore, at present there is no study that has prospectively assessed in a systematic way the effect of various levels of ambulatory blood pressure on cardiovascular outcome. Research is needed to more clearly understand the prognostic implications of average measures of blood pressure independently, dipper versus nondipper status, blood pressure load, and blood pressure variability, separately and in combination. Such studies are necessary not only in the essential hypertensive population, but also in patients with chronic renal failure (CRF). Despite these limitations, the results of two studies24,30,3’suggest that ambulatory blood pressure is superior to office blood pressure in predicting cardiovascular events. Perloff et a130.31 compared the relative value of office blood pressure and daytime (patient-activated) blood pressure on subsequent cardiovascular events in 1,076 patients. Ambulatory daytime blood pressure predicted new events in the short term and subjects whose ambulatory blood pressure was low relative to their clinic blood pressure had lower risk than those with higher ambulatory blood pressure. This study could not provide any prognostic information on sleep blood pressure or day-night differences because only awake blood pressure was recorded. In addition, no normotensive control group was included in this study. More recently, Verdecchia et a124reported on

Hypertensive

Patients

95th Percentiles

< 135185 < 120/70 < 130/80 either actual patient University Pr&s.4

and

Hypertension

i 39187 124f74 i 33fa1

diary

or standard

day

and

2 140/90 2 l25f75 2 135185 night

times

may

be used.

a group of 1,187 hypertensive subjects and 205 normotensive control subjects. All patients were off antihypertensive therapy for at least 4 weeks and underwent ambulatory blood pressure monitoring and measurement of their left ventricular mass at baseline. Treatment decisions were made by the primary care physicians with the goal of lowering office blood pressure to 5 140/90 mm Hg. All subjects were monitored over a mean of 3.2 years. Blinded interviewers obtained cardiovascular event rates by interview and also confirmed these by record review. The combined fatal and nonfatal cardiovascular events were higher in the ambulatory hypertensive group (Fig 2). After adjustment for other risk factors, the event rate was significantly higher in women with a nondipper blood pressure pattern compared with dippers with ambulatory hypertension. This relationship was not seen in the male hypertensive patients. Several other ongoing studies will provide fur-

‘1

v1 f 6I

Group

studied

Fig 2. Event-free survival in four groups of subjects: normotensive patients, white-coat hypertensive patients, dippers with ambulatory hypertension, and nondippers with ambulatory hypertension. Comparison between the survival curves was significant. (Reproduced with permission.“)

MANSOOR

ther prognostic information that will aid in the formulation of guidelines for the role of ambulatory blood pressure in clinical medicine. WHITE-COAT (ISOLATED OFFICE) HYPERTENSION AND ITS SIGNIFICANCE

One of the most controversial uses of ambulatory blood pressure monitoring is the detection of “isolated office” or “white-coat’ ’ hypertension. All consensus documents agreed that the detection of this entity is an important role for ambulatory blood pressure monitoring. However, consensus is needed about its definition, and much remains to be learned about its etiology and longterm outcome. Most studies examining the relationship of white-coat hypertension to hypertensive organ damage have concluded that this patient group has levels of hypertensive damage more similar to normotensive patients than established hypertensive patients. For example, white-coat hypertensive patients have left ventricular mass and function more similar to normotensive patients than ambulatory hypertensive patients.32-34 Furthermore, white-coat hypertensive subjects have microalbumin levels that are intermediate between normotensive and ambulatory hypertensive patients.35 Both the prospective studies in San Francisco3’ and Perugia” show strong evidence that subjects with normal ambulatory but high office blood pressure do not suffer excess cardiovascular events. However, neither of these two studies was randomized nor considered the effects of treatment on event rates. There have been conflicting reports about associated metabolic derangements in patients with white-coat hypertension. 36,37It is likely that if the subjects who are borderline hypertensive (ambulatory daytime blood pressure 2 135/85 mm Hg but < 140/90 mm Hg) are included in the white-coat hypertensive group, then a few will have evidence of hypertensive organ damage. Therefore, only subjects who have a repeatedly elevated office blood pressure and a normal ambulatory blood pressure should be considered to have isolated office hypertension. The recording of normal home blood pressure by these patients is reassuring that the diagnosis is white-coat hypertension. However, at least one ambulatory blood pressure recording that includes work and sleep

AND

WHITE

blood pressure is necessary to be certain that the patient is indeed normotensive. At this time, and until more is known about the cause and prognosis of isolated office or white-coat hypertension, it is wise to carefully monitor these patients and reinforce lifestyle modifications that will lower blood pressure. Treatment decisions should be based not only on the level of blood pressure, but also on absolute cardiovascular risk. However, if hypertensive end organ damage develops in such patients, then pharmacologic therapy should be initiated. AMBULATORY BLOOD PRESSURE IN DIVERSE CAUSES OF RENAL DISEASE Diabetes Mellitus

In diabetic subjects, most studies using ambulatory blood pressure monitoring have been cross-sectional and included small numbers of patients. These studies have focused largely on comparing the ambulatory blood pressure profiles of subjects with diabetes mellitus with those of subjects with essential hypertension or healthy controls. Other studies have examined the relationship of ambulatory and office blood pressure to microalbuminuria. It appears that the reproducibility of ambulatory blood pressure monitoring in diabetic subjects is good when the measurement conditions are standardized.38 Perhaps the most consistent finding in diabetic subjects is that both type 139d’ and type 242,43 diabetic subjects have higher nocturnal blood pressure than matched controls, and have an increased prevalence of nondipping even when the diabetic subjects are normotensive by office blood pressure.39,41s42 In diabetic patients with and without microalbuminuria,39 24-hour blood pressure is elevated compared with control subjects. It is tempting to speculate that this hidden nocturnal blood pressure elevation may be deleterious to these subjects. The relationship between the development of microalbuminuria and the presence of hypertension merits further study. In some studies,38A3 there is a correlation between ambulatory blood pressure and urinary albumin excretion. It appears that the elevation of blood pressure and the development of microalbuminuria occur synchronously (although not necessarily as cause and effect). One longitudinal study of 44 type 1

AMBULATORY

BP MONITORING IN RENAL DISEASE

diabetic patients (urinary albumin excretion rate < 20 pg/min) and 21 normotensive controls described the evolution of microalbuminuria and blood pressure.44 All subjects had office and ambulatory blood pressure as well as microalbumin measurements at baseline and after 3.1 years. At the start of the study, 24-hour ambulatory blood pressure in progressors (to overt microalbuminuria, > 20 pg/min) and nonprogressors and controls was identical. Over the study period, six diabetic subjects developed microalbuminuria, and these subjects also had a larger increase in 24-hour ambulatory systolic blood pressure than nonprogressors and normotensive patients. There was also a modest correlation between the change in albumin excretion with ambulatory but not office blood pressure. More data are needed on the relationship between ambulatory blood pressure levels and other diabetic organ dysfunction, such as retinopathy and nephropathy. Furthermore, whether intervention using ambulatory blood pressure as a guide to antihypertensive therapy in diabetic subjects is superior to office blood pressure in delaying complications has yet to be studied. Polycystic Kidney Disease Hypertension has been shown to be common and an important predictor for renal deterioration over time in patients with autosomal dominant polycystic kidney disease. Ambulatory blood pressure monitoring may therefore give insights into the development of hypertension and cardiac structure and function in these patients. Zeier et a145studied a group of 12 children and 12 young adults identified with the disease but who had normal renal function and were normotensive, and compared them with a control group of subjects. The children with polycystic disease had higher left ventricular mass than controls, but ambulatory blood pressure was similar. In the young adults with polycystic disease, both the left ventricular mass and ambulatory blood pressure were higher than in controls. Interestingly, all values of blood pressure and left ventricular mass were still in the normal range. As these investigators point out, this is somewhat similar to what happens in many subjects with type 1 diabetes, Additional study of blood pressure pro-

597

files and the development of hypertension needed in this group of patients.

is

USE OF AMBULATORY BLOOD PRESSURE IN SUBJECTS WITH CHRONIC RENAL DISEASE

A limited number of studies with ambulatory blood pressure monitoring have been completed in subjects with renal disease. Most of these studies are small and cross-sectional, and have analyzed such issues as overall blood pressure control, the prevalence of dippers and nondippers, and the relationship of hypertension to volume status in dialysis patients. Fewer studies using ambulatory blood pressure have examined hypertension in the postrenal transplant period. Ambulatory Blood Pressure Projiles in Subjects With Chronic Renal Disease Studies of subjects with CRF. Because of the association of elevated nocturnal blood pressure with increased cardiovascular risk, some researchers have studied blood pressure profiles in subjects with chronic renal disease not requiring renal replacement therapy. Portaluppi et a146 monitored blood pressure in 30 hospitalized hypertensive patients (mean age, 45 years) who were not undergoing dialysis but had advanced renal disease (mean creatinine clearance, 25 mL/ min) and in 30 matched essential hypertensive patients with normal renal function (creatinine clearance, 114 mUmin). Most of the patients with renal disease had glomerulonephritis (13 patients) or chronic pyelonephritis (12 patients). The two groups were matched for 24-hour blood pressure, but the subjects with renal disease were found to have a much smaller decline in sleep blood pressure compared with the essential hypertensive patients (12.7/12.9 mm Hg v 2.7/3.7 mm Hg; P < 0.001). The patients with chronic renal disease also had higher heart rates during the nighttime period. These investigators concluded that patients with renal insufficiency have a blunted blood pressure profile. However, they used an unusual definition of day (8 AM to 8 PM) and night (8 PM to 8 AM) to calculate the change in blood pressure. Similar results were obtained by Cottone et a14’ who compared ambulatory blood pressure and plasma catecholamines in 12 subjects with chronic renal insufficiency (creatinine clearance,

598

20 to 63 mL/min) and 16 subjects with essential hypertension and normal renal function. In the renal disease group, half of the patients had a greater than 10% decline in diastolic blood pressure at night (definition of dipper used by the researchers), while 75% of the essential hypertensive patients were dippers. Interestingly, Cottone et al also found that plasma norepinephrine levels were higher in the subjects with chronic renal disease and that norepinephrine levels were inversely correlated with renal function. No differences were seen in levels of norepinephrine among dippers and nondippers. These investigators suggested that sympathetic activity was a contributor to hypertension in subjects with CRF. Baumgart et a148reported similar findings in a study of 20 subjects with CRF (serum creatinine, > 4 mg/dL) who were compared with 20 controls with similar office blood pressure. The awakesleep difference was significantly lower in the subjects with renal disease (9.9/9.7 mm Hg v 24.Y20.7 mm Hg; P = 0.01) and the heart rate decline also was less (8.4 beats/min v 14.7 beats/ min; P < 0.05). One investigator reports that evening but not morning antihypertensive therapy may restore the day-night blood pressure variation in subjects with advanced renal disease who are nondippers. This effect may not apply to all antihypertensive patients, and may depend on pharmacokinetic properties of the drug used. However, Rosansky et a15’ found no relationship between reduced renal function and the extent of nocturnal blood pressure decline. These investigators studied 53 older veteran hypertensive men with a mean age of 60 years who were divided into three groups according to mean creatinine clearance: greater than 108 mL/min (group A), 44.8 mL/min (group B), and 11.9 mL/ min (group C). All the subjects had been off antihypertensive therapy for 4 weeks at the time of the 24-hour ambulatory blood pressure monitoring study. Approximately half the subjects were black. Rosansky et al analyzed their data using a fixed day-night separation (7 AM to 11 PM as day and 11 PM to 7 AM as night). The three groups were comparable in all ambulatory averages except for heart rate; group C had higher heart rates than group B. There also were no differences in the percentage change in blood pressure at night across the three groups. Group

MANSOOR

AND

WHITE

C also showed higher upright norepinephrine levels compared with the other two groups. A regression model revealed that race was the most significant variable, although it only accounted for a small amount of the variance. The average percentage decline in mean arterial blood pressure in the three groups was 7.1%, 7.8%, and 7.4%, respectively. Unfortunately, this study did not have a control group; it would have been very interesting to have comparative data on the normal percentage decline in blood pressure in 60-year-old veterans. These few studies suggest that some subjects with predialysis renal disease may have hidden hypertension at night and that ambulatory blood pressure monitoring may be useful in selected patients with CRF. Ambulatory blood pressure studies of hemodialysis anaYor peritoneal dialysis patients. In

general, studies of hemodialysis patients have been cross-sectional, and comparison has been made to subjects with CRF, continuous ambulatory peritoneal dialysis (CAPD) patients, or subjects with essential hypertension. An early study performed ambulatory blood pressure monitoring in 20 hemodialysis patients as well as in age-, sex-, and office blood pressure-matched controls.46 The hemodialysis subjects had higher sleep blood pressure, smaller nocturnal decline in blood pressure, and faster heart rates than the control group. The results of Luik et a151were similar. These investigators studied 20 patients on chronic hemodialysis (10 normotensive [postdialysis blood pressure < 140/90 mm Hg] and 10 hypertensive [postdialysis blood pressure 2 140/90 mm Hg]), 20 CAPD patients (11 normotensive and nine hypertensive), and 20 control subjects with normal renal function (nine normotensive and 11 hypertensive). Antihypertensive medications were discontinued for 3 weeks, and hemodialysis patients had achieved optimal dry weight as judged by echographic vena cava measurement. All subjects underwent ambulatory blood pressure monitoring (hemodialysis patients for 3 days, CAPD patients and controls for 24 hours). The investigators used a criterion of a day-night difference of less than 5 mm Hg in mean arterial pressure as a definition of nondipper. The groups were comparable demographically. Hemodialysis and CAPD patients showed

AMBULATORY

BP MONITORING IN RENAL DISEASE

a smaller decline in nocturnal diastolic blood pressure than controls (9 mm Hg in dialysis patients and 9 mm Hg in CAPD patients v 15 mm Hg in controls; P = 0.003 and 0.01, respectively). Other studies52-55have found similar blunting of nocturnal blood pressure decline in hemodialysis subjects. However, this finding is not universal, and some patients on dialysis retain their daynight blood pressure pattern if it is examined by cosinor analysis.54 Ojanen et a156studied the influence of volume changes and atria1 natriuretic peptide and ambulatory blood pressure in 10 subjects on chronic hemodialysis (median age, 57 years). Only two subjects were hypertensive. These researchers found that the day-night blood pressure differences were 11.3/7.1 mm Hg on the dialysis day and 19.3/8.7 mm Hg on the second interdialytic day. On the dialysis day, 80% of subjects had a significant day-night difference in systolic blood pressure and 67% had a difference in diastolic blood pressure. Unfortunately, this study had no control group for 24-hour blood pressure comparisons. There have been conflicting data on the relationship of volume changes to the increase in blood pressure in the interdialytic period. One study5’ of children on hemodialysis also showed an impaired day-night blood pressure profile. Clausen et als8 compared ambulatory blood pressure in 10 CAPD patients (mean age, 60 years) with 10 controls matched for clinic blood pressure. The CAPD patients had higher nocturnal and 24-hour blood pressure than did the control subjects. In addition, the nocturnal decline in blood pressure was attenuated in the dialysis group compared with the control group (2 mm Hg v 10 mm Hg; P < 0.01). In contrast, Korzets et al” found a preserved circadian pattern to the blood pressure in 55% of CAPD patients and emphasized that different results will be obtained when different methods are used to calculate the day-night blood pressure difference. Despite the limited number of ambulatory blood pressure studies in the dialysis population, there appear to be some common preliminary findings. A single 24-hour period of ambulatory monitoring is probably inadequate to ascertain the awake-sleep difference in blood pressure in dialysis patients. Most studies have found that hemodialysis patients as well as peritoneal dial-

599

ysis patients have a less than expected decline in blood pressure at night. Patients on hemodialysis who are not hypertensive appear to retain the circadian rhythm in nature and degree. Control of Blood Pressure in Dialysis Patients The dialysis patient has multiple elements that may affect blood pressure, including fluid retention, activation of the renin-angiotensin system, sympathetic overactivity, use of erythropoietin (EPO), and antihypertensive therapy. Hypertension is a potent independent risk factor for cardiovascular events in subjects on dialysis. Therefore, studies are urgently needed to understand the optimal ways to monitor and treat hypertension in this population. Rodby et a154found little relationship between predialysis and postdialysis blood pressure and ambulatory blood pressure averages. Both predialysis and postdialysis blood pressure readings were not good estimates of the ambulatory blood pressure averages. Similarly, in a study of 53 adult hemodialysis patients, Cheigh et a155found that blood pressure was unacceptably elevated for approximately half of the interdialytic period. These investigators suggested that the practice of withholding antihypertensive medications before dialysis should be reassessed and that multiple readings during the interdialytic cycle were needed to properly assess overall blood pressure control. When a subset of patients was studied after medication adjustment based on ambulatory blood pressure recordings, significant reductions in blood pressure loads were found. Another study from Kooman et al@ attempted to find the best office blood pressure that approximates ambulatory blood pressure in dialysis patients. These investigators studied 22 patients with various levels of blood pressure and found that postdialytic blood pressure was closer to average interdialytic blood pressure than predialytic blood pressure. They also confirmed previous findings that in the several hours before dialysis, blood pressure increases substantially. Interdialytic weight gain, however, may not be the most important factor in this increase in blood pressure. The interdialytic weight gain and its influence on interdialytic blood pressure were studied in 10 normotensive and 10 hypertensive hemodialysis patients.5’ Dry weight was esti-

MANSOOR

600

mated using echocardiography of the vena cava. The weight gain during a 3-day interdialytic period was greater than during a 2-day interdialytic period, but no difference in ambulatory blood pressure was found. The available data on blood pressure control in dialysis patients indicate that current methods of monitoring hypertension are suboptimal. However, these patients show marked blood pressure variability, and studies are necessary to determine the best ways to monitor and manage hypertension. EPO AND HYPERTENSION IN UREMIC SUBJECTS

EPO has improved the well-being of subjects with anemia of CRF and markedly reduced the need for blood transfusions. However, early in its use it was shown to cause an increase in blood pressure, especially at higher doses.61 The pathophysiology of this increase in blood pressure is probably multifactorial.61 Ambulatory blood pressure monitoring has helped in understanding the effects of EPO therapy on overall blood pressure, nighttime blood pressure, and circadian blood pressure variation in patients on various types of renal replacement therapy.62-65 Van de Borne et a162studied 13 chronic hemodialysis patients (only two taking antihypertensive therapy) before and after 3 to 4 months of EPO therapy. Although predialysis and postdialysis blood pressure did not change, ambulatory daytime systolic blood pressure, nighttime diastolic blood pressure, and blood pressure load increased significantly and awake-asleep blood pressure difference was attenuated. In a similar study,63 13 anemic patients (eight normotensive and five with borderline systolic hypertension) on hemodialysis were studied with ambulatory blood pressure monitoring before and after 3 months of subcutaneous EPO therapy (30 to 40 U/kg three times weekly). Not only was office blood pressure higher after correction of anemia, but there also was a clinically significant increase in ambulatory blood pressure of a large magnitude (16/10 mm Hg for 24-hour blood pressure). The blood pressure load for both awake and asleep periods was also higher after EPO. Patients who were nondippers before treatment with EPO were not more likely to have an increase in

AND

WHITE

blood pressure. Patients with higher systolic blood pressure before treatment were more likely to show an increase in blood pressure following EPO. In a similar study@ of 32 anemic hemodialysis subjects who were treated with 4,500 IU/wk EPO for 8 weeks, a significant increase in daytime and nighttime blood pressure was observed. Again, in this study, office blood pressure was not a reliable way to detect this increase in blood pressure. The role of an expanded plasma volume in the genesis of EPO-associated hypertension was studied65 in 24 patients with CRF (12 on hemodialysis, eight on CAPD, and four with advanced renal disease [creatinine clearance, < 25 mL/ min]). Isotopically measured red blood cell and plasma volumes and ambulatory blood pressure profiles were analyzed at baseline and at the achievement of target hematocrit levels (EPO dose was 40 to 50 U/kg subcutaneously three times weekly). The patients were divided for analytical purposes into those who had EPO-induced hypertension (mean daytime systolic blood pressure increase >20 mm Hg or diastolic blood pressure > 10 mm Hg) and those who did not. In the subjects who developed hypertension, plasma volume was lower at the end of the study. Daytime ambulatory blood pressure was increased the most by EPO. These results and those of Imai et ala contradict the idea that EPO-induced hypertension is due to hypervolemia. It therefore seems that increases in blood pressure occur with EPO use; these increases may not be detectable by clinic measurements, but are easily identified with ambulatory blood pressure monitoring. Such increases should attract the attention of nephrologists, and closer monitoring of subjects receiving EPO is recommended. The effects of EPO on daytime and nighttime blood pressure require further study. RELATIONSHIP OF AMBULATORY BLOOD PRESSURE AND HYPERTENSIVE COMPLICATIONS IN CRF

Left ventricular hypertrophy is common in subjects with reduced renal function, but there are few studies examining the relationship with office and ambulatory blood pressure. In one recent study66 of 85 patients with CRF of diverse etiology, ambulatory blood pressure was a

AMBULATORY

BP MONITORING

IN RENAL DISEASE

stronger correlate than office blood pressure to left ventricular mass index. Furthermore, in the overall study group, the only blood pressure parameter found to be independently related to left ventricular mass index was ambulatory systolic blood pressure, the other significant variables being male gender, body mass index, and hemoglobin concentration. Similar results have been found in patients undergoing dialysis. Erturk et a15*performed an interesting study in 40 nondiabetic dialysis patients (mean age, 32 years) who were clinically believed to have achieved their dry weight. Most patients were hypertensive and receiving antihypertensive therapy. All subjects were on thriceweekly 4-hour dialysis and were biochemically stable. Clinic blood pressure was the average blood pressure taken both before and after a dialysis session. Standard echocardiographic studies were performed and read by observers blinded to the blood pressure readings. Ambulatory blood pressure was measured the day after midweek dialysis and continued until the next dialysis session. It was found that 90% of the subjects had echocardiographic left ventricular hypertrophy. After a stepwise linear regression analysis, systolic blood pressure load emerged as the unique independent predictor for left ventricular mass index and septal thickness. Blood pressure load was defined here as the integrated area under the curve above threshold values (146/9 1 mm Hg for day and 127/79 mm Hg for night). A similar study67 was done in subjects (mean age, 50 years) who had been receiving 24 hours of dialysis weekly (8 hours three times weekly) for at least 10 years. None of the subjects were diabetic, and only four were on antihypertensive therapy. The subjects underwent ambulatory blood pressure monitoring starting 12 to 14 hours after their midweek dialysis and echocardiography at least 12 hours after dialysis. Despite the impressive history of long-duration dialysis and good blood pressure control, 76% of subjects had echocardiographic left ventricular hypertrophy. The major findings were that the average clinic blood pressure (systolic and diastolic) over the previous 2 years was correlated to septal thickness, posterior wall thickness, and end-diastolic diameter/ posterior wall thickness ratio and that 24-hour diastolic blood pressure was correlated to poste-

601

rior wall thickness and end-diastolic diameter/ posterior wall thickness ratio. Ambulatory systolic blood pressure was not correlated to left ventricular hypertrophy. Unfortunately, the investigators did not analyze awake and asleep blood pressure separately, nor did they report if the awake-asleep difference was related to the presence of left ventricular hypertrophy. Undoubtedly, cardiac mass in dialysis patients is affected by multiple factors, including hypertension, age, body weight, volume overload, secondary hyperparathyroidism, and anemia. Because left ventricular hypertrophy has negative prognostic risk, further work is urgently needed to define the contribution of hypertension to the progression of left ventricular hypertrophy. Furthermore, it is necessary to better understand the contributors to the high prevalence of left ventricular hypertrophy in this patient population. AMBULATORY BLOOD PRESSURE MONITORING IN RENAL TRANSPLANTATION

Because cardiovascular disease is a significant contributor to death in renal transplant patients, there is interest in the causes and treatment of hypertension in this population. In this group of subjects, blood pressure may be elevated by graft dysfunction or the use of immunosuppressive therapy. Ambulatory blood pressure monitoring has been used very selectively to study various aspects of hypertension in this population. Baumgart et a14* included in their study 21 renal transplant patients, of whom 16 had elevated office blood pressure. Of the group, 17 patients were receiving cyclosporine, four were on azathioprine, and all were on corticosteroids. Most of the patients’ native renal disease was glomerulonephritis (12 patients). The renal transplant patients had a reduced awake-asleep difference compared with control subjects with normal renal function but matched for clinic blood pressure. A reduced nocturnal blood pressure dip was also found in a study by Lipkin et a16* who performed ambulatory blood pressure monitoring in 28 normotensive renal transplant subjects (mean age, 48 years) who were at least 1 year postrenal transplantation and had good graft function (mean creatinine clearance, 70 mL/min). Twelve of the patients were receiving azathioprine and prednisone only; the remainder were receiving

MANSOOR 0 Dippers (%) 0 Non-Dippers (%)

Time

after

transplantation

(months)

Fig 3. The percentage of dippers and nondippers with time after renal transplantation. The proportion of nondippers decreases over time. (Reproduced with permission of Williams and Wilkins. Gatzka CD, Schobel HP, Klingbeil AU, et al: Normalization of circadian blood pressure profiles after renal transplantation. Transplantation 591270-1274, 1995.88)

cyclosporine as part of their immunosuppressive treatment. All patients were normotensive (clinic blood pressure, < 140/90 mm Hg). The 24-hour blood pressure exceeded the clinic blood pressure in the group. Clinic blood pressure did not differ between the cyclosporine-treated and non-cyclosporine-treated groups, but the cyclosporinetreated group had higher daytime and nighttime blood pressure. The group receiving cyclosporine had a higher prevalence of left ventricular hypertrophy. Ambulatory systolic, rather than diastolic, blood pressure correlated with left ventricular mass index. Twenty-five percent of the entire group (five of 16 in the cyclosporine-treated group and two of the non-cyclosporine-treated group) had a nondipping status (< lo/5 mm Hg). The left ventricular mass index was greater in the nondippers than in the dippers (124 g/m’ v 89 g/m*; P < 0.05). Gatzka et a169 studied the relationship of the circadian blood pressure to length of time after renal transplant. They studied 45 patients after renal transplantation using ambulatory blood pressure monitoring, dividing the group into tertiles representing time after transplantation (early phase, < 7 months; intermediate phase, 7 to 11 months; late phase, > 1 year), and found that the prevalence of dippers (reduction of mean arterial blood pressure by 2 10%) increased as the length of time after transplant increased (Fig 3). Of many clinical factors analyzed, only the length of time after dialysis corre-

AND

WHITE

lated with the extent of nocturnal blood pressure decline. Renal transplant patients on both cyclosporine and FK506 have impaired blood pressure variation7’ although the latter drug may be associated with less hypertensive therapy. Diabetic subjects with renal failure who undergo combined kidney-pancreas transplantation71 also have a blunted decline in nocturnal blood pressure. Ten subjects (mean age, 33 years; none requiring insulin) had their blood pressure studied for 48 hours at various times after transplantation. All subjects were receiving a triple regimen of cyclosporine, azathioprine, and steroids. Five patients were taking antihypertensive medications. Eighty percent of patients had a higher blood pressure at night compared with daytime, and all subjects were nondippers. The explanation for these striking results may lie in the fact that all these subjects were insulin-dependent diabetics and probably had autonomic neuropathy. Additionally, it was found that daynight blood pressure variation was related to sodium bicarbonate intake. In summary, studies in renal transplant patients mirror the findings for subjects undergoing dialysis. There is a high level of nocturnal hypertension, and a significant number of subjects are nondippers. These findings require further study because hypertension is an important cardiovascular risk factor in renal transplant patients. CONCLUSION

The availability of ambulatory blood pressure monitoring should aid the nephrologist in understanding the blood pressure profile in subjects with renal disease and those requiring renal replacement therapy. Although the available studies using the methodology are few and many uncontrolled, the findings are remarkably consistent. Blood pressure assessment and follow-up in dialysis and renal transplant patients appear to be suboptimal. Most studies indicate a blunting of nocturnal decline in blood pressure in subjects on dialysis and in renal transplant patients. A better understanding of the reproducibility and problems of using the methodology in dialysis patients is needed. It is likely that we will see an increase in the use of ambulatory monitoring in the chronic renal disease population.

AMBULATORY

BP

MONITORING

IN RENAL

DISEASE

REFERENCES 1. Joint National Committee: The 1993 report of the Joint National Committee on detection, evaluation and treatment of high blood pressure. Arch Intern Med 153:154-185, 1993 2. Sheps SG, Pickering TG, White WB, Weber MA, Clement DL, Krakoff LR, Messerli FH, Perloff D: American College of Cardiology position statement; Ambulatory blood pressure monitoring. J Am Co11Cardiol 23:1511-1513, 1994 3. National high blood pressure education program working group report on ambulatory blood pressure monitoring. Arch Intern Med 150:2270-2280,199O 4. Staessen JA, Bieniaszewski L, O’Brien ET, Fagard R: What is normal blood pressure on ambulatory monitoring? Nephrol Dial Transplant 11:241-245, 1996 5. O’Brien E, Atkins N: A comparison of the British Hypertension Society and Association for the Advancement of Medical Instrumentation protocols for validating blood pressure measuring devices: Can the two be reconciled? J Hypertens 12:1089-1094, 1994 6. White WB, Berson AS, Robbins C, Jamieson MJ, Prisant LM, Rocella E, Sheps SG: National standard for measurement of resting and ambulatory blood pressures with automated sphygmomanometers. Hypertension 21:504-509, 1993 7. O’Brien E, Petrie J, Littler W, de Swiet M, Padfield PL, Altman D: Short report: An outline of the revised British Hypertension Society protocol for the evaluation of blood pressure monitoring devices. J Hypertens 11:677-679, 1993 8. Mansoor G, White WB: Contribution of ambulatory blood pressure monitoring to the conduct and design of clinical trials. J Cardiovasc Risk 1:136-142, 1994 9. White WB, Lund-Johannsen P, McCabe EJ, Omvik P: Assessment of four portable ambulatory blood pressure monitors and measurement by clinicians versus intraarterial blood pressure at rest and during exercise. Am J Cardiol 65:60-66, 1990 10. Sheps SG, Canzanello VJ: Current role of automated ambulatory blood pressure and self measured blood pressure determinations in clinical practice. Mayo Clin Proc 69: lOOO1005, 1994 11. Pieper C, Warren K, Pickering TG: A comparison of ambulatory blood pressure and heart rate at home and work on work and non-work days. J Hypertens 11:177-183, 1993 12. Stewart MJ, Gough K, Padfield PL: The accuracy of automated blood pressure measuring devices in patients with controlled atria1 fibrillation. J Hypertens 13:297-300, 1995 13. Mallion, JM, de Gaudemaris R, Baguet JP, Azzouzi L, Quesada JL, Sauzeau C, Siche JP, Tremel F, Boutelant S: Acceptability and tolerance of ambulatory blood pressure measurement in the hypertensive patient. Blood Press Monit 1:197-203, 1996 14. Coats AJS, Clark SJ, Conway J: Analysis of ambulatory blood pressure data. J Hypertens 9:s 19-S2 1, 199 1 (suppl

8) 15. White WB: Analysis of ambulatory blood pressure data in antihypertensive drug trials. J Hypertens 9:S27-S32, 1991 (suppl 1) 16. Gnecchi-Ruscone T, Piccaluga E, Guzzetti S, Contini M, Montano N, Nicolis E: Morning and Monday: Critical

603 periods for the onset of acute myocardial infarction. Eur Heart J 15:882-887, 1994 17. Gatzka CD, Schmieder RE: Improved classification of dippers by individualized analysis of ambulatory blood pressure profiles. Am J Hypertens 8:666-671, 1995 18. Rosansky SJ, Menachety SJ, Wagner CM, Jackson K: The effect of sleep intervals on analysis of 24-h ambulatory blood pressure data. Am J Hypertens 8:672-675, 1995 19. Peixoto AJ, Mansoor GA, White WB: Effects of actual versus arbitrary awake and sleep times on analyses of 24-h blood pressure. Am J Hypertens 8:676-680, 1995 20. Bursztyn M, Mekler J, Wachtel N, Ben-Ishay D: Siesta and ambulatory blood pressure monitoring. Am J Hypertens 7:217-221, 1994 21. Pickering TG: The clinical significance of diurnal blood pressure variation: Dippers and nondippers. Circulation 81:700-702, 1990 22. Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C, Benemio G, Boldrini F, Porcellati C: Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 81:528-536, 1990 23. O’Brien E, Sheridan J, O’Malley K: Dippers and nondippers. Lancet 2:397, 1988 24. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Batistelli M, Guerrieri M, Gatteschi C, Zampi I, Santuci C, Reboldi G: Ambulatory blood pressure; an independent predictor of prognosis in essential hypertension. Hypertension 24:793-801, 1994 25. Staessen JA, Bieniaszewski L, O’Brien E, Gosse P, Hayashi H, Imai Y, Kawasaki T, Otsuka K, Palatini P, Thijs L, Fagard R: Nocturnal blood pressure fall on ambulatory monitoring in a large international database. Hypertension 29:29-39, 1997 26. Schillaci G, Verdecchia P, Borgioni C, Ciucci A, Gattobigio R, Sacchi N, Benemio G, Porcellati C: Predictors of diurnal blood pressure changes in 2042 subjects with essential hypertension. J Hypertens 14: 1167- 1173, 1996 27. O’Brien E, Staessen J: Normotension and hypertension as defined by 24-hour ambulatory blood pressure monitoring. Blood Press 4:266-282, 1995 28. White WB: Hypertensive target organ involvement and 24-hour ambulatory blood pressure measurement, in Waeber B, O’Brien E, O’Malley K, Brunner H (eds): Ambulatory Blood Pressure Monitoring. New York, NY, Raven, 1994, pp 47-60 29. Mansoor GA, White WB: Ambulatory blood pressure and cardiovascular risk stratification. J Vast Med Biol 5:6168, 1994 30. Perloff D, Sokolow M, Cowan RM: The prognostic value of ambulatory blood pressures. JAMA 249:2792-2798, 1983 31. Perloff D, Sokolow M, Cowan RM, Juster RP: Prognostic value of ambulatory blood pressure measurements: Further analyses. J Hypertens 7:S3-SlO, 1989 (suppl 3) 32. Gosse P, Promax H, Durandet P, Clementy J: White coat hypertension; no harm for the heart. Hypertension 22:766-770, 1993 33. White WB, Schulman P, McCabe EJ, Dey HM: Average daily blood pressure, not office blood pressure, deter-

604 mines cardiac function in patients with hypertension. JAMA 261:873-877, 1989 34. Hoegholm A, Kristensen KS, Bang LE, Nielsen JW, Madsen NH: Left ventricular mass and geometry in patients with established hypertension and white-coat hypertension. Am J Hypertens 6:282-286, 1993 35. Hoegholm A, Bang LE, Kristensen KS, Nielsen JW, Holm J: Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension. Hypertension 24:101-105, 1994 36. Marchesi E, Perani G, Falaschi F, Negro C, Catalan0 0, Ravetta V, Finardi G: Metabolic risk factors in white coat hypertensives. J Hum Hypertens 8:475-479, 1994 37. Weber MA, Neutel JM, Smith DH, Graettinger WF: Diagnosis of mild hypertension by ambulatory blood pressure monitoring. Circulation 90:2291-2298, 1994 38. Hansen KW, Poulsen PL, Christiansen JS, Mogensen CE: Determinants of 24-h blood pressure in IDDM patients. Diabetes Care 18529-535, 1995 39. Lurbe A, Redon J, Pascual JM, Tacons J, Alvarez V, Bathe DC: Altered blood pressure during sleep in normotensive subjects with type 1 diabetes. Hypertension 21:227-235, 1993 40. Page SR, Manning G, Ingle AR, Hill P, Millar-Craig MW, Peacock I: Raised ambulatory blood pressure in type 1 diabetes with incipient microalbuminuria. Diabet Med 11:877-882, 1994 41. Gilbert R, Phillips P, Clarke C, Jerums G: Day-night blood pressure variation in normotensive, normoalbuminuric type 1 diabetic subjects. Diabetes Care 17:824-827, 1994 42. Fogari R, Zoppi A, Malamani GD, Lazzari P, Destro M, Corradi L: Ambulatory blood pressure monitoring in normotensive and hypertensive type 2 diabetics. Am J Hypertens 6:1-7, 1993 43. Chau NP, Bauduceau B, Chanudet X, Larroque P, Gautier D: Ambulatory blood pressure in diabetic subjects. Am J Hypertens 7:487-491, 1994 44. Poulsen PL, Hansen KW, Mogensen CE: Ambulatory blood pressure in the transition from normo- to microalbuminutia, Diabetes 43:1248-1253, 1994 45. Zeier M, Geberth S, Schmidt KG, Mandelbaum A, Ritz E: Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease. J Am Sot Nephrol 3:1451-1457, 1993 46. Portaluppi F, Montanari L, Massari M, Di Chiara V, Capanna M: Loss of nocturnal decline of blood pressure in hypertension due to chronic renal failure. Am J Hypertens 4:20-26, 1991 47. Cottone S, Panepinto N, Vadala A, Zagarrigo C, Galione P, Volpe V, Cerasola G: Sympathetic overactivity and 24-hour blood pressure pattern in hypertensives with chronic renal failure. Ren Fail 17:751-758, 1995 48. Baumgart P, Walger P, Gemen S, von Eiff M, Raidt H, Rahn KH: Blood pressure elevation during the night in chronic renal failure, hemodialysis and after renal transplantation. Nephron 57:293-298, 1991 49. Portaluppi F, Vergnani L, Manfredini R, degli Uberti EC, Fersini C: Time-dependent effect of isradipine on the

MANSOOR

AND

WHITE

nocturnal hypertension in chronic renal failure. Am J Hypertens 8:719-726, 1995 50. Rosansky SJ, Menachery SJ, Wagner CM, Jackson K: Circadian blood pressure variation versus renal function. Am J Kidney Dis 26:716-721, 1995 51. Luik AJ, Gladziwa U, Kooman JP, van Hooff JP, de Leeuw PW, van Bortel LM, Leunissen KML: Influence of inter-dialytic weight gain on blood pressure in hemodialysis patients. Blood Purif 12:259-266, 1994 52. Erturk S, Ertug AE, Ates K, Duman N, Aslan SM. Nergisoglu G, Diker E, Erol C, Karatan 0, Erbay B: Relationship of ambulatory blood pressure monitoring data to echocardiographic findings in hemodialysis patients. Nephrol Dial Transplant 11:2050-2054, 1996 53. Jones MA, Sharpstone P, Dallyn PE, Kingswood JC: Reduced nocturnal blood pressure fall is similar in continuous ambulatory peritoneal dialysis to that in hemodialysis and undialysed end-stage renal disease. Clin Nephrol42:273-275, 1994 54. Rodby RA, Vonesh EF, Korbet SM: Blood pressures in hemodialysis and peritoneal dialysis using ambulatory blood pressure monitoring. Am J Kidney Dis 23:401-411, 1994 55. 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, 1992 56. Ojanen S, Pietila K, Pastemack A: Plasma atria1 natriuretic peptide, body weight and twenty-four-hour blood pressure monitoring in chronic hemodialysis patients. Nephron 73:174-178, 1996 57. Peco-Antic A, Pejcic I, Stojanov V, Parezanovic V, Kostic M: Ambulatory blood pressure monitoring in chronic hemodialysis children with end-stage renal disease. Nephron 72~739-740, 1996 58. Clausen P, Feldt-Rasmussen B, Ladefoged J: Circadian variation of blood pressure in patients with chronic renal failure on continuous ambulatory peritoneal dialysis. Stand J Clin Lab Invest 55:193-200, 1995 59. Korzets Z, Erdberg A, Golan E, Bemheim J: Does diurnal variation in blood pressure exist in CAPD patients? Nephrol Dial Transplant 9:274-276, 1994 60. Kooman JP, Gladziwa U, Backer G, Wijnen JA, Bortel LV, Luik AJ, de Leeuw PW, Hooff JPV, Leunissen ML: Blood pressure during the inter-dialytic period in hemodialysis patients: Estimation of representative blood pressure values. Nephrol Dial Transplant 7:917-923, 1992 61. Nowicki M: Erythropoietin and hypertension. J Hum Hypertens 9:81-88, 1995 62. Van de Borne P, Tielemans C, Vanherweghem JL, Degaute JP: Effect of recombinant erythropoietin therapy on ambulatory blood pressure and heart rate in chronic hemodialysis patients. Nephrol Dial Transplant 7:45-49, 1992 63. Lebel M, Kingma I, Grose JH, Langlois S: Effect of recombinant human erythropoietin therapy on ambulatory blood pressure in normotensive and in untreated borderline hypertensive hemodialysis patients. Am J Hypertens 8:545551, 1995 64. Imai Y, Sekino H, Fujikura Y, Munakata M, Minami N, Hashimoto J, Sakuma H, Watanabe N, Misawa S, Nishiyama A, Abe K: Pressor effect of recombinant human eryth-

AMBULATORY

BP

MONITORING

IN RENAL

DISEASE

ropoietin: Results of ambulatory blood pressure monitoring and home blood pressure measurements. Clin Exp Hypertens 17:485-506, 1995 65. Jones MA, Kingswood JC, Dallyn PE, Andrew M, Cheetham A, Burwood R, Sharpstone P: Changes in diurnal blood pressure variation and red cell and plasma volumes in patients with renal failure who develop erythropoietin-induced hypertension. Clin Nephrol 44: 193-200, 1995 66. Tucker B, Fabbian F, Giles M, Thuraisingham C, Raine AEG, Baker LR: Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic renal failure. Nephrol Dial Transplant 12:724-728, 1997 67. Covic A, Goldsmith DJ, Georgescu G, Venning MC, A&ill P: Echocardiographic findings in long-term long-hour hemodialysis patients. Clin Nephrol 45:104-l 10, 1996

68. Lipkin GW, Tucker B, Giles M, Raine AE: Ambulatory blood pressure and left ventricular mass in cyclosporinand non-cyclosporin treated renal transplant recipients. J Hypertens 11:439-442, 1993 69. Gatzka CD, Schobel HP, Klingbeil AU, Neumayer HH, Schmieder RE: Normalization of circadian blood pressure profiles after renal transplantation. Transplantation 59:1270-1274, 1995 70. Hohage H, Bruckner D, Arlt M, Buchholz B, Zidek W, Spieker C: Influence of cyclosporine A and FK506 on 24h blood pressure monitoring in kidney transplant recipients. Clin Nephrol 45:342-344, 1996 7 1. Marx MA, Gardner SF, Ketel BL: Diurnal blood pressure variation in kidney-pancreas transplant recipients. Am J Hypertens 9:823-827, 1996