DIALYSIS TECHNICAL NOTE

Evaluating Volume Status

in Hem,odialysis Patients
John K. Leypoldt and Alfred K. Cheung
Accurate determination of the volume and distribution of body fluids in end stage renal disease
patients will permit improved assessment of dry weight and strategies for optimal fluid removal.
Certain biochemical markers and anatomical measures have been proposed as markers of dry weight,
but these markers primarily reflect the volume of the intravascular compartment and may not reflect
total body volume status. Noninvasive determination of total body water and extracellular fluid
volumes using bioimpedance analyses has also been proposed for assessment of dry weight, but such
determinations do not yet have sufficient accuracy for routine use. Several devices have been recently
developed for continuously monitoring changes in blood volume on-line during routine hemodialysis.
Such blood volume monitors cannot be used to determine dry weight directly; however, continuous
monitoring of blood volume can be used to detect fluid overload because intradialytic changes in
blood volume are small in hemodialysis patients who are overhydrated. Furthermore, continuous
monitoring of blood volume can be used to predict symptoms resulting from intradialytic hypovole-
mia. The combined use of blood volume monitoring and time-dependent ultrafiltration and dialysate
sodium profiles will be used increasingly in the future to assist in the prevention of hypotension and
symptoms that result from intradialytic hypovolemia, especially when automated systems for
controlling intradialytic blood volume are individualized and shown to be safe and effective.
© 1998 by the National Kidney Foundation, Inc.
Index Words: Hemodialysis; bioimpedence; blood volume monitoring; dry weight; fluid overload;
intradialytic complications.

T he development of improved, especially

noninvasive and on-line, methods for de-
termining total body volume status and the
distribution of body fluids in end-stage renal
disease (ESRD) patients will permit improved
assessment of dry weight and strategies for
optimal fluid removal. The objectives of this
article are to review the distribution of fluids
within the body and to evaluate new ap-
proaches for determining volume status and
the distribution of body fluids in ESRD pa-
tients. Only limited references to the use of
such determinations in assessing urea distribu-
tion volume will be discussed. Further, empha-
sis will be placed on applications in chronic
hemodialysis (HD) patients, but certain stud-
ies in peritoneal dialysis (PO) patients will also
be described.
From the Research and MedIcal Services, Veterans Affairs
Medical Center; and Departments of Intemal Medicine and
Bioel1g11leering, University of Utah, Salt Lake City, UT.
Supported by DVA Merit Review Funds al1d the Dialysis
Research FoundatIOn, Ogdel1, UT.
Address correspondence to /olm K. Leypoldt, PhD, Dumke
Bu71d11lg 535, Ul1iversity of Utah, Salt Lake City, UT 84112,
© 1998 by the National Kidl1ey Foundation, 111c,
1073-4449/98/0501-0008$3,00/0
Fluid Distribution Within Normal
Individuals
Approximately 60% of the body is composed
of water; two thirds of total body water is
intracellular, and one third is extracellular (Fig
1).1,2 Extracellular fluid can be further divided
into the plasma compartment, the interstitial
compartment, and the transcellular com part-
ment.1 The transcellular compartment is nor-
mally a minor fraction of extracellular fluid
and is often neglected; however, it may be
important in ESRD patients because it in-
cludes fluid within the peritoneal cavity. Ap-
proximately one fifth of extracellular fluid is
located within plasma, and four fifths is lo-
cated extravascularly. The volume of total
body water can be determined with an accu-
racy of about 3% (:1::1.5 L) by determining the
dilution of a marker substance that distributes
throughout this space, such as isotopic water
or antipyrine.1,3 As measured by such tech-
niques, the fraction of body weight that con-
sists of water varies considerably among indi-
viduals and depends on several factors: age,
gender, body fat content, and the presence of
altered physiological or pathophysiological
states. 4 The determination of extracellular fluid
volume by dilution techniques is less rigorous
because there does not exist a marker sub-

64 Advances in Renal Replacement Therapy, Vol 5, No 1 (January),1998: pp 64-74

 Dialysis Technical Note: Volume in Dialysis Patients
Total Body Water (50-70% body weight)
Intracellular Water
(30-400/0 body weight)
Figure 1. The distribution of fluids within the body of a nonuremic individual.
stance that is exclusively confined within this
compartment. 4 Dilution techniques are, how-
ever, impractical for routine evaluation of
ESRD patients.
It is often assumed that the distribution of
body fluids within ESRD patients is similar to
that in normal individuals, but this contention
has not been extensively examined. Further-
more, when fluid is rapidly removed from the
vascular compartment during HD, intercom-
partmental shifting of intracellular and extra-
cellular fluids occurs. The changes that occur
in extracellular fluid volume can result in
disequilibrium syndrome, hypotension, and
other symptoms, and these complications re-
flect the physiological incompatibility of rapid
fluid removal during HD.
Assessment of Dry Weight and Fluid
Overload
Definitions of Dry Weight
The amount of fluid that should be removed
during HD is often difficult to evaluate and is
65
Extracellular Water
(20% body weight)
Interstitial
16%
clinically determined by assigning a dry weight
to each patient. From a conceptual standpoint,
dry weight is the postdialysis weight where
the patient is in a state of normohydration.
Because the volume status of ESRD patients
cannot be directly measured, dry weight is
instead defined clinically to minimize the oc-
currence of signs and symptoms indicating
overhydation or underhydation.
With one approach, dry weight is defined as
the postdialysis weight at which the blood
pressure is lowered into the presumed normal
range «150 mmHg systolic or <90 mmHg
diastolic), if possible, without the develop-
ment of intradialytic hypotension. In addition,
the patient should not exhibit signs of pulmo-
nary or peripheral edema. The emphasis of
this approach is on the blood pressure, but the
postdialysis weight may be greater than that
representing a state of normohydration. The
failure to remove sufficient fluid when using
this approach could be detrimental because
chronic fluid overload adds burden to the
heart.
66 Leypoldt and Cheung
In another approach recently summarized
by Charra et al, 5postdialysis weight is progres-
sively decreased and fluid removal is progres-
sively increased during long (5 to 6 hours) HD
treatments until symptoms of intradialytic hy-
povolemia and hypotension are consistently
observed. Severe muscle cramps frequently
occur during this process. After several weeks,
however, blood pressure gradually decreases
to a level at which all antihypertensive medica-
tions can be eliminated, and a dry weight is
established. This process has been called prob-
ing for dry weight and can be an unpleasant
experience for both the patient and the medi-
cal staff.5 The main advantage of this approach
is that total body fluid volumes are reduced to
levels that avoid overhydration. Whether this
is advantageous for patient survival has not
been tested in controlled clinical trials, but the
excellent outcome of dialysis patients in Tas-
sin,6 where this approach is used extensively,
should not be discounted. This approach is
only used at some dialysis centers; the use of
the former approach is more widespread, espe-
cially when short «4 hours) treatment times
are used.
Clinical wisdom suggests that dry weight is
often not assessed accurately during routine
HD therapy, and this notion is supported by
the observation that hypertension is present in
a significant fraction of chronic HD patients.7,s
Although the mechanisms leading to hyperten-
sion are multifactorial, fluid overload is fre-
quently cited as a major contributing factor. 9,10
Therefore, several approaches are being devel-
oped to more accurately assess dry weight and
HD patient volume status.
Biochemical Markers of Dry Weight
Plasma levels of atrial natriuretic peptide
(ANP) are elevated in HD patients,11 and
extracorporeal removal of fluid has been shown
to reduce plasma ANP levels.1 2 This relation-
ship between fluid removal and plasma ANP
levels resulted in the proposal that postdialy-
sis plasma levels of ANP can be used to assign
patient dry weightP More recently, Lauster et
al have suggested that postdialysis plasma
levels of the ANP second messenger, cyclic
guanosine 3',5'-monophosphate (cGMP), may
be a more reliable index of dry weight and that
HD patients with a postdialysis plasma level
of cGMP less than 20 pmol / mL are at their dry
weights. 14,15 When postdialysis weight was
lowered in HD patients who had postdialysis
plasma levels of cGMP greater than 20 pmol/
mL, a decrease in the postdialysis plasma level
of cGMP was observed in virtually all pa-
tients. 15 Consistent with the hypothesis that
cGMP is a useful dry weight marker, clinical
signs of fluid overload (such as edema in the
legs, distended jugular veins, or pulmonary
rales on auscultation) in continuous ambula-
tory peritoneal dialysis (CAPD) patients were
also observed to be associated with elevated
plasma levels of cGMP.1 6 These observations
suggest that plasma cGMP levels may be
related to volume status in ESRD patients and
therefore used to assess dry weight.
There are several concerns with the use of
plasma levels of cGMP to assess ESRD patient
volume status. First, cGMP is excreted by the
kidney; therefore, plasma levels of cGMP may
be influenced by residual renal function, Sec-
ond, cGMP is dialyzed to a certain extent
across both the peritoneal and HD mem-
branes. Third, results of laboratory biochemi-
cal tests are not immediately available and
cannot be easily adapted for routine clinical
evaluation of volume status. Fourth, plasma
cGMP levels are probably influenced only by
intravascular but not extravascular volume
status. Finally, Leunissen et aP7 have sug-
gested that because both ANP and cGMP are
released by myocytes of the left atrium, their
plasma levels can only be used to assess
volume status in patients with normal left
atrial hemodynamics.
Anatomical Measures of Dry Weight
Cheriex et aPS have shown that the diameter of
the inferior vena cava, measured noninva-
sively using ultrasound, is nonlinearly related
to mean right atrial pressure in HD patients.
Because central venous pressure and right
atrial pressure are considered indicators of
right ventricular function and body volume
status, these investigators proposed that the
diameter of the vena cava could be used to
evaluate dry weight in HD patients. It should
be noted, however, that central venous pres-
sure may not be a reliable indicator of overall
volume status, because it only reflects the
volume of the intravascular compartment.
 Dialysis Technical Note: Volume in Dialysis Patients
Work by Tetsuka et aP9 has indeed shown
that inferior vena cava diameter depends
largely on blood volume. These investigators
measured blood volume and inferior vena
cava diameter during and after HD and noted
that these parameters correlated closely with
each other both during and after HD therapy.
Similar findings have been reported more
recently by Katzarski et aI.2° To be an effective
indicator of dry weight, however, the diameter
of the vena cava at the end of HD must reflect
total body water volume, not simply blood
volume.
Direct Determination of Fluid
Compartment Volumes
The feasibility of using direct measurements of
total body water volume and body composi-
tion in HD patients depends on two factors.
First, the accuracy of the method for assessing
the fluid compartment volume is critically
important because small alterations in hydra-
tion status relative to the total volume of fluid
can be clinically significant. Second, it is neces-
sary to compare the measured fluid compart-
ment volumes with those predicted for an
individual patient to determine hydration sta-
tus because normal body fluid content is vari-
able from patient to patient. Previous work
has focused primarily on the former concern.
Determination of total body water volume: Bio-
impedance analyses. Total body water volume
in ESRD patients can be estimated by several
different formulas. For example, this volume
has been frequently estimated simply as a
fraction of body weight, such as 58% of body
weight. Alternatively, total body water can be
more accurately estimated by anthropometric
equations that account for age, gender, height,
and weight, such as those described by Hume
and Weyers 21 and Watson, Watson, and Batt. 22
Nevertheless, such calculations only estimate
average values and are inaccurate for many
clinical applications because of considerable
interpatient variability and because the appli-
cability of these equations to ESRD patients is
unclear.
There is increasing interest in using the
electrical properties of the body to determine
fluid compartment volumes. The resistance to
current flow through the body is proportional
to the geometry of the current pathway and
67
can be used to determine total body water
volume and the distribution of body water
into extracellular and intracellular compart-
ments. When using this approach, a low ampli-
tude alternating current is typically applied
across the body using electrodes attached to
the arms and legs, and the voltage drop across
the electrodes is measured to calculate the
resistance to current flow. Because alternating
currents are used, the resistance to current
flow includes both capacitive and resistive
elements; thus, the term impedance is more
accurate than resistance and this approach is
called bioelectrical impedance or bioimped-
ance.
When a single high-frequency current is
used (single frequency bioimpedance), only
total body water volume can be calculated.
When a range of frequencies is used (multiple
frequency bioimpedance or bioimpedance
spectroscopy), it is possible to calculate both
total body water and extracellular fluid vol-
ume. The principle underlying bioimpedance
spectroscopy is that current at very high fre-
quencies penetrates cell membranes, and the
impedance at high frequencies therefore re-
flects total body water volume, whereas cur-
rent at very low frequencies should not pen-
etrate cell membranes, and the impedance at
low frequencies therefore reflects the volume
of extracellular fluids. The measured imped-
ance values from bioimpedance spectroscopy
are first extrapolated to infinitely high and
infinitely low frequencies, and the correspond-
ing resistances are related to total body water
volume and extracellular fluid volume, respec-
tively. A conceptual model of body tissues
may also be used to calculate body volumes
directly from the determined resistance values
as performed by the commercial instrument
from Xitron Technologies (San Diego, CA).
Single frequency bioimpedance has been
validated against the dilution volume of isoto-
pic water in normal and obese individuals. 23,24
Recent work in both HD25,26 and PD27,28 pa-
tients has shown that single frequency bio-
impedance estimates of total body water vol-
ume correlate highly with those determined
by the dilution of marker substances; however,
single frequency bioimpedance underesti-
mates the total body water volume in HD
patients. 25,26 Furthermore, the standard devia-
68 Leypoldt and Cheung
tion between bioimpedance and dilution vol-
umes was high, approximately 3 L.25,26 It has
therefore been suggested that single frequency
bioimpedance estimates of total body water
volume are too insensitive to be clinically
useful for estimating dry weight29 or urea
volume for the assessment of the dose of PDP
It should be noted that the above studies were
performed at a current frequency of 50 kHz, a
value that is not high enough to completely
penetrate cells. Ho et apo tested a range of
frequencies for determining total body water
volume and showed that a frequency of 148
kHz gave the best agreement with dilution
volumes. Although total body water volumes
determined at this frequency were not statisti-
cally different from those determined by dilu-
tion of isotopic water, the variability between
the two techniques was considerable (half of
the differences were greater than 2 L). The
above description of single frequency bioelec-
trical impedance refers to measurements per-
formed under equilibrated conditions, not dur-
ing HD. During a HD treatment, changes in
impedance are affected more by changes in the
composition of blood than by alterations in
total body fluid content. 31 Indeed, changes in
total body water during a single HD treatment
are overestimated by single frequency bio-
impedance at 50 kHz when compared with
changes in body weight. 25,26
Determination of total body water and extracel-
lular fluid volumes: Bioimpedance spectroscopy.
Bioimpedance spectroscopy has been applied
for simultaneously determining total body
water and extracellular fluid volumes in
chronic HD patients by several investiga-
torS. 32-38 The pioneering work of Kouw et aP2
first showed that this approach could be used
to calculate total body water and extracellular
fluid volumes before and after HD by measur-
ing electrical conductivity across a segment of
the lower leg to multiple current frequencies.
These investigators reported that calculated
values of intracellular fluid volume were lower
in HD patients than in normal controls and
that the postdialysis extracellular fluid volume
was similar in HD patients to that in normal
controls.
A significant concern with the use of bio-
impedance spectroscopy to assess fluid com-
partment volumes is that it has not been
validated in healthy subjects nor in ESRD
patients. Total body water and extracellular
fluid volumes calculated using bioimpedance
spectroscopy correlate highly with volumes
determined by the dilution of marker sub-
stances, but good agreement between volume
estimates is not always observed. 33,38 The re-
sults recently published by Katzarski et aP6 are
shown in Table 1. These investigators deter-
mined total body water and extracellular fluid
volume in chronic HD patients and showed
that these volumes measured postdialysis in
normotensive HD patients were similar to
those measured in control subjects, observa-
tions that are consistent with those reported by
Kouw et aI.32 These investigators further
showed that postdialysis values of total body
water and extracellular fluid volume in hyper-
tensive HD patients were higher than those in
normotensive HD patients, suggesting that
fluid overload is a significant cause of hyper-
tension in chronic HD patients. Based on
expected values (compare Table 1 with Fig 1),
Katzarski et aP6 concluded that bioimpedance
spectroscopy underestimated total body water
volume and overestimated extracellular fluid
volume, a contention consistent with results
from other recent studies. 33,38 Bioelectrical spec-
troscopy is noninvasive and easily applied in
the HD clinic; however, further studies are
necessary before this approach can be recom-
mended for routine determination of total
Table 1. Total Body Water (TBW) and
Extracellular Fluid Volume (ECV) Determined by
Bioimpedance Spectroscopy of Normotensive and
Hypertensive Chronic HD Patients
Hemodialysis Patients
Nonnal
Normotensive Hypertensive Subjects
%TBWbefore
HD 47.6 ± 5.8 50.3 ± 6.5
%TBWafter
HD 45.7 ± 6.4 48.8 ± 7.8 48.1 ± 5.0
% ECVbefore
HD 26.8 ± 3.5 29.4 ± 3.6
% ECV after
HD 24.6 ± 3.5 27.0 ± 4.0 25.4 ± 2.3
NOTE: Values are expressed in percentage of body weight.
Mean ~ SD are shown.
Reprinted by permission of Oxford University Press from
Katzarski K, Charra B, Laurent G, et al: Multifrequency
bioimpedance in assessment of dry weight in haemodialy-
sis. Nephrol Dial Transplant 11:20-23, 1996 (supp12).36
 Dialysis Technical Note: Volume in Dialysis Patients
body water and extracellular fluid volume to
assess dry weight.
Evaluation of hydration status. Before such
determinations of fluid compartment volumes
can be used to assess hydration status and
therefore dry weight, they must be compared
with independent estimates of the expected
volume for each patient when normohy-
drated. Kouw et aP2 proposed that HD pa-
tients could be categorized as underhydrated,
normohydrated, or overhydrated based on the
postdialysis volume of extracellular fluid com-
pared with that in control subjects. This ap-
proach is limited because it does not account
for the normal variability in body composition
among individual patients. Others39Ao have
estimated patient hydration status by compar-
ing total body water volumes determined in
HD patients with those calculated by an anthro-
pometric method. Dionisio et al40 have also
estimated patient hydration status as the differ-
ence between total body water determined by
bioimpedance and that estimated by the an-
thropometric equation of Watson, Watson, and
Batt.22 The accuracy of these estimates of hydra-
tion status is difficult to evaluate but is crucial
when using this approach to assess dry weight.
Continuous Monitoring of Blood Volume
Several devices have been recently developed
to continuously monitor changes in blood
volume during HD,41 and the physical prin-
ciples of the different types of devices have
been recently reviewed and compared. 42 Some
devices offer certain advantages over others
based on practical considerations, but each
device can be used to determine changes in
intradialytic blood volume.
Detection of fluid overload. Recent work has
shown that continuous blood volume monitor-
ing can be used to detect fluid overload caused
by overestimation of dry weight. Similar to the
caveats described above for biochemical and
anatomical parameters, it must be emphasized
that measurements of changes in blood vol-
ume during HD may not always be an accu-
rate reflection of extravascular volume status.
During routine HD, where fluid removal rates
often exceed the vascular rate of refilling,
changes in blood volume and extracellular
volume are often not proportional. Although it
has been proposed that extracellular volume
acts as a single compartment during HD,43 this
69
is rarely observed. Therefore, changes in blood
volume by themselves cannot be used to deter-
mine dry weight.
Lopot et al44 have recently proposed that
continuous blood volume monitoring can be
used to identify chronic HD patients who are
believed to be at dry weight as assessed by
routine physical examination but in fact are
fluid overloaded. These investigators hypoth-
esized that dry weight was too high if no
significant decrease in intradialytic blood vol-
ume occurred, because refilling of the intravas-
cular compartment is rapid when extracellular
tissues are overhydrated. 45 In their study, 21
out of 66 (32%) chronic HD patients exhibited
no significant decrease in blood volume dur-
ing the entire HD session. Additional measure-
ments of inferior vena cava diameter and data
obtained using bioimpedance spectroscopy
(vide supra) suggested that extracellular fluid
volume in these patients at the end of the
session was indeed high, consistent with the
concept that these patients were fluid over-
loaded.
This hypothesis is consistent with the known
relationship between blood volume and extra-
cellular volume (Fig 2).2 When extracellular
volume is normal, deviations in blood volume
from normal are proportional to those in the
extracellular compartment. When extracellu-
lar volume is excessive and edema is present,
for example as a result of renal failure, re-
moval of fluid from blood will produce only
small changes in blood volume because of
rapid refilling from the extracellular space
(plateau phase of the curve). It should be
noted that this relationship applies when the
blood and extracellular fluid compartments
are in equilibrium and may only be approxi-
mate in HD patients when fluid removal is
rapid.
Steuer et al46 directly tested this hypothesis
of Lopot et al. They identified 10 chronic HD
patients who had less than a 5% decrease in
intradialytic blood volume but were consid-
ered at dry weight as reflected by maintenance
of blood pressure as low as possible without
consistent symptomatic hypotension and the
absence of peripheral or pulmonary edema.
For the next 6 weeks, dry weight was intention-
ally decreased in O.5-kg-per-session incre-
ments in these patients. This intervention led
to increased ultrafiltered volume by an aver-
70 Leypoldt and Cheung
7
6
o between blood volume and
o 10 20
Extracellular Volume (liters)
age of 47% and a decreased dry weight in 6 of
the 10 patients by 0.80 ± 0.62 (SD) L, without a
significant increase in intra dialytic symptoms.
Wilkie et al47 have reported similar but more
impressive results. They intentionally in-
creased fluid removal in 11 out of 28 patients
who initially had little to no decrease in intra-
dialytic blood volume and observed a reduc-
tion in dry weight of 2.7 kg in the subsequent 2
to 9 dialysis sessions. They also reported a
reduction in antihypertensive medications in 2
of their study patients. It should be noted that
in both of the above studies, there were some
patients who had only small changes in blood
volume during HD yet could not tolerate
increased fluid removal. This could be because
of severely compromised cardiac function and
therefore an inability to tolerate even small
changes in blood volume without hypoten-
sion. Nevertheless, these observations suggest
that continuous blood volume monitoring is
helpful in detecting fluid overload in patients
who are considered to be at dry weight as
assessed by routine physical examination.
Prediction and Prevention of Symptoms
During Hemodialysis
Intradialytic hypotension is attributed, at least
in part, to decreases in blood volume. 48 During
Figure 2. The relationship
extracellular volume when
30 40 these compartments are in
equilibrium. Reprinted and
adapted with permission
from Guyton and Hal1. 2
the past decade, interest in understanding the
role of changes in blood volume in governing
complications during HD has been revived
because of the development of noninvasive
and on-line devices for monitoring intradia-
lytic changes in blood volume. Early, prelimi-
nary results were promising and suggested
that varying the ultrafiltration rate according
to intradialytic changes in blood volume could
be used to reduce the incidence of hypotension
and muscle cramps.49
More recent studies have examined whether
changes in blood volume can be used to
predict hypotension or other symptoms dur-
ing chronic HD therapy. For example, de Vries
et al reported that the magnitude of the de-
crease and the rate of decrease in blood vol-
ume, both normalized for ultrafiltration vol-
ume, were greater in HD patients who
experienced hypotensive events than in pa-
tients who did not experience such events. 50,51
Additional studies by these same investigators
showed that intra dialytic changes in blood
volume were related to total body volume
status. 52 The intra dialytic decrease in blood
volume was small for overhydrated patients
and large for dehydrated patients, as expected
because tissue hydration is a major determi-
nant of the plasma refilling rate. 45,53 Further-
more, the frequency of hypotensive episodes
 Dialysis Technical Note: Volume in Dialysis Patients
in the dehydrated patients was significantly
greater than that in normohydrated or overhy-
drated patients. 52 It should be noted, however,
that these investigators determined hydration
status using bioimpedance spectroscopy, the
accuracy of which has been questioned (vide
supra). Similar findings have been reported by
others, 54 whereas some investigators were un-
able to identify a relationship between intradia-
lytic changes in blood volume and dialysis-
induced hypotension. 55
Steuer et al 56 continuously monitored intra-
dialytic changes in hematocrit, as a reflection
of changes in blood volume, and correlated
these findings with intradialytic morbid events
(IMEs), defined as hypotension, muscle
cramps, and lightheadedness. It was observed
that the rate of change in blood volume imme-
diately preceding the IME was indeed higher
in chronic HD patients who experienced intra-
dialytic morbidity than in patients who did
not. The correlation between the magnitude of
the change in blood volume and IMEs was,
however, variable from patient to patient, as
illustrated in Table 2. IMEs occurred in certain
patients with a change of only 4 hematocrit
units (11 % decrease in blood volume), but in
others IMEs did not occur until the hematocrit
increased by 12 units (35% decrease in blood
volume). These investigators hypotheSized that
intradialytic morbidity occurred at a patient-
specific blood volume or hematocrit threshold,
Table 2. Hematocrit (H) Threshold When
IMEs Occurred
MeanH
Change Before
Patient No.ofIMEs [ME From Start
No. During Study H Threshold of Treatment
1 9 40 ± 1.6
2 6 38 ± 1.3
3 7 31 ± 2.7
4 4 46 ± 1.9
5 2 44 ± 0.5
6 3 38 ± 2.2
7 9 44 ± 0.5
8 3 40 ± 1.2
9 6 38 ± 0.4
3 49 ± 0.9
10
11 2 36 ± 0.5
12 7 49 ± 2.2
NOTE. H threshold value given as mean :!: SD.
Abbreviation: IME, intradialytic morbid events.
Reprinted with permission from Steuer et al. 56
71
which is similar to the proposal by Kim et al
that symptomatic hypotension during HD oc-
curred when blood volume reached a critical
minimum value. 48 Furthermore, these data
suggested that intradialytic morbidity could
be minimized if the treatment could be tai-
lored such that the hematocrit threshold was
avoided.
The possibility of reducing intradialytic mor-
bidity by using continuous monitoring of blood
volume was subsequently tested using an
experimental protocol that was conducted in
two phases. 57 During the first phase, each
patient was monitored in consecutive treat-
ment sessions, and symptoms with respect to
intradialytic hematocrit readings were re-
corded. The hematocrit threshold for each
patient was therefore established in this phase.
During the second phase, the ultrafiltration
rate was varied throughout the session such
that the intradialytic hematocrit was targeted
below the individualized hematocrit thresh-
old. This experimental intervention resulted in
a 50% reduction in intradialytic symptoms
without altering the total amount of fluid
removed during the session. The results from
this study suggested that the hematocrit thresh-
old concept is valid and may be useful in
reducing symptoms caused by intradialytic
hypovolemia. It should be emphasized, how-
ever, that this study was limited to only 5
patients and that further studies will be neces-
sary to determine what fraction of the HD
population may benefit from this technique
and how to identify such patients.
Other investigators have used automatic
feedback control systems to guide fluid re-
moval during HD based on changes in intradia-
lytic blood volume. 58,59 Figure 3 shows an
8 example of changes in blood volume during
4 HD guided by such a system and demon-
4
strates the feasibility of this approach. Such
12
10 systems are not yet commercially available but
8 will ultimately use ultrafiltration and dialysate
6 sodium profiling to produce optimal changes
4 in blood volume during HD.59-62 Two aspects
5
11
of this approach deserve further emphaSiS.
6 The first concern relates to the definition of the
9 optimal blood volume profile during HD.
Based on the studies by Steuer et al56 described
immediately above, this optimal blood vol-
ume profile should be patient specific. The
72 Leypoldt and Cheung

Blood 8.8
volume
changes [ Actual BV changes
(%) -5.8

-18.8
Desired BV
changes

8 68 128 188 248

TIME (",ins)
Figure 3. The dependence of blood volume on time during HD when using a system to automatically control
the blood volume profile. The desired and actual changes in blood volume are shown as indicated. The actual
changes in intradialytic blood volume were controlled by varying the ultrafiltration rate and dialysate sodium
concentration. Reprinted by permission of Oxford University Press from Santoro A, Mancini E, Paolini F,
Zucchelli P: Blood volume monitoring and control. Nephrol Dial Transplant 11:42-47,1996 (suppI2).59

second concern is that minimizing the de-
crease in blood volume during HD by increas-
ing dialysate sodium may increase total body
sodium content and result in enhanced inter-
dialytic fluid intake and hypertension. 63 There-
fore, demonstration of such automatic control
systems should ideally include long-term
evaluation of dry weight, sodium balance,
hypertension control, and cardiac function.
Acknowledgment
We are grateful to W. Cameron Chum lea, PhD from
Wright State University, Columbus, OH, and Kras-
simir Katzarski, MD and Jonas Bergstrom, MD from
the Karolinska Institute, Stockholm, Sweden for
their helpful suggestions.
References
1. Val tin H, Schafer JA: Renal Function (ed 3). Boston,
MA, Little, Brown and Company, 1995
2. Guyton AC, Hall JE: Textbook of Medical Physiology
(ed 9). Philadelphia, PA, Saunders, 1996
3. Pitts RF: Physiology of the Kidney and Body Fluids
(ed 3). Chicago, IL, Year Book Medical Publishers,
1974
4. Fanestil DD: Compartmentation of body water, in
Narins RG (ed): Clinical Disorders of Fluid and
Electrolyte Metabolism (ed 5). New York, NY, McGraw-
Hill, 1994, pp 3-20
5. Charra B, Laurent G, Chazot C, et al: Clinical assess-
ment of dry weight. Nephrol Dial Transplant 11:16-19,
1996 (suppI2)
6. Charra B, Calemard E, Ruffet M, et al: Survival as an
index of adequacy of dialysis. Kidney Int 41:1286-
1291,1992
7. Cheigh JS, Milite C, Sullivan JF, et al: Hypertension IS
not adequately controlled in hemodialysis patients.
Am J Kidney Dis 19:453-459, 1992
8. Salem MM: Hypertension in the hemodialysis popula-
tion: A survey of 649 patients. Am J Kidney Dis
26:461-468,1995
9. Mailloux LU, Bellucci AG, Napolitano B, Mossey RT:
The contribution of hypertension to dialysis patient
outcomes. Apoint of view. ASAIO J 40:130-137, 1994
10. Fisbane S, Natke E, Maesaka JK: Role of volume
overload in dialysis-refractory hypertension. Am J
Kidney Dis 28:257-261,1996
11. Saxonhofer H, Gnadinger MP, Weidmann P, et al:
Plasma levels and dialysance of atrial natriuretic
peptide in terminal renal failure. Kidney Int 32:554-
561, 1987
12. Petersen J, Li Cc, Bishop-Abney N, Seniw CM: Hemo-
dynamic and atrial natriuretic peptide responses to
fluid removal and reinfusion in hemodialYSis patients.
Trans ASAIO 34:509-511, 1988
13. Talartschlik J, Eisenhauer T, Voth E, et al: Ist der
Plasma-ANP-Spiel ein Index fur die Volumenexpan-
sion bei Dialysepatienten? Z Kardiol 77:72-77, 1988
(suppl)
14. Lauster F, Gerzer R, Weil J, et al: Assessment of dry
body-weight in haemodialysis patients by the bio-
chemical marker cGMP. Nephrol Dial TrarlSplant 5:356-
361, 1990
 Dialysis Technical Note: Volume in Dialysis Patients
15. Lauster F, Hille H-J, Gerzer R, Schiff! H: The posdia-
lytic plasma cyclic guanosine 3':5'-monophosphate
level as a measure 9f fluid overload in chronic hemodi-
alysis. J Am Soc NephroI2:1451-1454, 1992
16. Lauster F, Heim JM, Drummer C, et al: Plasma cGMP
level as a marker of the hydration state in renal
replacement therapy. Kidney Int 43:557-559, 1993
(suppI41)
17. Leunissen KML, Kouw P, Kooman JP, et al: New
techniques to determine fluid status in hemodialyzed
patients. Kidney Int 43:550-S56, 1993 (suppI41)
18. Cheriex EC, Leunissen KML, Janssen JHA, et al:
Echography of the inferior vena cava is a simple and
reliable tool for estimation of' dry weight' in haemodi-
alysis patients. Nephrol Dial Transplant 4:563-568,
1989
19. Tetsuka T, Ando Y, Ono S, Asano Y: Change in inferior
vena caval diameter detected by ultrasonography
during and after hemodialysis. ASAIO J 41:105-110,
1995
20. Katzarski KS, Nisell J, Randmaa I, et al: A critIcal
evaluation of ultrasound measurement of inferior
vena cava diameter in assessing dry weight in normo-
tensive and hypertensive hemodialysis patients. Am J
Kidney Dis 30:459-465, 1997
21. Hume R, Weyers E: Relationship between total body
water and surface area in normal and obese subjects. J
clin PathoI24:234-238, 1971
22. Watson PE, Watson ID, Batt RD: Total body water
volumes for adult males and females estimated from
simple anthropometric measurements. Am J Clin Nutr
33:27-39,1980
23. Kushner RF, Kunigk A, Alspaugh M, et al: Validation
of bioelectrical-impedance analysis as a measurement
of change in body composition in obesity. Am J Clin
Nutr 52:219-232, 1990
24. Segal KR, Burastero 5, Chun A, et al: Estimation of
extracellular and total body water by multiple-
frequency bioelectrical-impedance measurement. Am
J Clin Nutr 54:26-29,1991
25. Kong CH, Thompson CM, Lewis CA, et al: Determina-
tion of total body water in uraemic patients by
bioelectrical impedance. Nephrol Dial Transplant 8:716-
719, 1993
26. Chertow GM, Lowrie EG, Wilmore DW, et al: Nutri-
tional assessment with bioelectrical impedance analy-
sis in maintenance hemodialysis patients. J Am Soc
NephroI6:75-81, 1995
27. Wong K-C, Xiong D-W, Kerr PG, et al: Kt /V in CAPD
by different estimations of V. Kidney Int 48:563-569,
1995
28. de Fijter WM, de Fijter CWH, Oe PL, et al: Assessment
of total body water and lean body mass from anthro-
pometry, Watson formula, creatinine kinetics, and
body electrical impedance compared with antipyrine
kinetics in peritoneal dialysis patients. Nephrol Dial
Transplant 12:151-156,1997
29. Kushner RF, de Vries PMJM, Gudivaka R: Use of
bioelectrical impedance analysis measurements in the
clinical management of patients undergoing dialysis.
Am J Clin Nutr 64:5035-509S, 1996 (suppl)
30. Ho LT, Kushner RF, Schoeller DA, et al: Bioimpedance
73
analysis of total body water in hemodialYSIS patients.
Kidney lnt 46:1438-1442,1994
31. Sinning WE, de Oreo PB, Morgan AL, Brister EC:
Monitoring hemodialysis changes with bioimped-
ance. What do we really measure? A5AIO J 39:M584-
M589, 1993
32. Kouw PM, Olthof CG, ter Wee PM, et al: Assessment
of post-dialysis dry weight: An application of the
conductivity measurement method. Kidney Int 41:440-
444, 1992
33. Smye SW, Norwood HM, Buur T, et al: Comparison of
extra-cellular fluid volume measurement in children
by 99'fcm -DPTA clearance and multi-frequency imped-
ance techniques. Physiol Meas 15:251-260, 1994
34. Cha K, Chertow GM, Gonzalez J, et al: Multifrequency
bioelectrical impedance estimates the distribution of
body water. J Appl Physiol 79:1316-1319, 1995
35. Jabara AE, Mehta RL: Determination of fluid shifts
during chronic hemodialysis using bioimpedance spec-
troscopy and an in-line hematocrit monitor. ASAIO J
41:M682-M687, 1995
36. Katzarski K, Charra B, Laurent G, et al: Multifre-
quency bioimpedance in assessment of dry weight in
haemodialysis. Nephrol Dial Transplant 11:20-23,1996
(suppI2)
37. Fisch BJ, Spiegel DM: Assessment of excess fluid
distribution in chronic hemodialysis patients using
bioimpedance spectroscopy. Kidney lnt 49:1105-1109,
1996
38. De Lorenzo A, Andreoli A, Matthie J, Withers P:
Predicting body cell mass with blOimpedance by
using theoretical methods: A technological review. J
Appl PhysioI82:1542-1558, 1997
39. Thylen P, Ericsson F, Odar-Cederlof I, Kjellstrand CM:
Hypertension profiling by total body water (TBW)
determinations in patients on chronic hemodialysis.
Int J Artif Organs 14:18-22, 1991
40. Dionisio P, Valenti M, Bergia R, et al: Influence of the
hydration state on blood pressure values in a group of
patients on regular maintenance hemodialysis. Blood
Purif 15:25-33,1997
41. Schneditz D, Levin NW: Non-invasive blood volume
monitoring during hemodialysis: Technical and physi-
ological aspects. Semin Dial 10:166-169, 1997
42. Polaschegg H-D, Levin NW: Hemodialysis machines
and monitors, in Jacobs C, Kjellstrand CM, Koch KM,
Winchester JF (eds): Replacement of Renal Function
by Dialysis (ed 4). Dordrecht, Netherlands, Kluwer
Academic, 1996, pp 333-379
43. Mishkin GJ, Bosch JP, Velasquez MT, et al: Quantifica-
tion of dry weight (DW) by continuous hematocrit
(HCT) monitoring in hemodialysis patients. J Am Soc
NephroI7:1522, 1996 (abstr)
44. Lopot F, Kotyk P, Blaha J, Forejt J: Use of continuous
blood volume monitoring to detect inadequately high
dry weight. Int J Artif Organs 19:411-414,1996
45. Koomans HA, Geers AB, Mees EJD: Plasma volume
recovery after ultrafiltration in patients with chronic
renal failure. Kidney Int 26:848-854,1984
46. Steuer R, Germain M, Leypoldt J, Cheung A: En-
hanced fluid removal guided by blood volume moni-
74 Leypoldt and Cheung
toring during chronic hemodialysis. ASAIO J 42:83,
1996 (abstr)
47. Wilkie ME, Li~dley EJ, Edwards L, et al: Improved
ultrafiltration control using an online blood volume
monitor (BVM). Nephrol Dial Transpl 11:A202, 1996
(abstr)
48. Kim KE, Neff M, Cohen B, et al: Blood volume changes
and hypotension during hemodialysis. Trans ASAIO
16:508-514, 1970
49. Stiller S, Wirtz D, Waterbar F, et al: Less symptomatic
hypotension using blood volume controlled ultrafiltra-
tion. Trans ASAIO 37:M139-M141, 1991
50. de Vries J-PPM, Olthof CG, Visser V, et al: Continuous
measurement of blood volume during hemodialysis
by an optical method. ASAIO J 38:M181-M185, 1992
51. de Vries JPPM, Donker AJM, de Vries PMJM: Preven-
tion of hypovolemia-induced hypotension during he-
modialysis by means of an optical reflection method.
Int J Artif Organs 17:209-214, 1994
52. de Vries J-PPM, Kouw PM, van der Meer NJM, et al:
Non-invasive monitoring of blood volume during
hemodialysis: Its relation with post-dialytic dry weight.
Kidney Int 44:851-854, 1993
53. Wizeman V, Leibinger A, Mueller K, Nilson A: Influ-
ence of hydration state on plasma volume changes
during ultrafiltration. Artif Organs 19:416-419, 1995
54. Rockel A, Abdelhamid S, Fiegel P, et al: Characteriza-
tion of "refilling types" by continuous blood volume
monitoring during hemodialysis. Kidney Int 43:S67-
S69, 1993 (suppI41)
55. Maeda K, Morita H, Shinzato T, et al: Role of hypovo-
lemia in dialysis-induced hypotension. Artif Organs
12:116-121, 1988
56. Steuer RR, Leypoldt JK, Cheung AK, et al: Hematocrit
as an indicator of blood volume and a predictor of
intradialytic morbid events. ASAIO J 40:M691-696,
1994
57. Steuer RR, Leypoldt JK, Cheung AK, et al: Reducing
symptoms during hemodialysis by continuously mom-
toring the hematocrit. Am J Kidney Dis 27:525-532,
1996
58. Santoro A, Mancini E, Paolini F, et al: Automatic
control of blood volume trends during hemodialysis.
ASAIO J 40:M419-M422, 1994
59. Santoro A, Mancini E, Paolini F, Zucchelli P: Blood
volume monitoring and control. Nephrol Dial Trans-
plant 11:42-47, 1996 (suppI2)
60. Mann H, Stefanidis I, Reinhardt B, Stiller S: Prevention
of haemodynamic risks by continuous blood volume
measurement and control. Nephrol Dial Transplant
11:48-51, 1996 (suppI2)
61. Kelly TD: Kinetics of intradialytic disequilibria: The
problem, the causes, and new methods for the allevia-
tion of patient morbidity. Nephrol Dial Transplant
11:3-9, 1996 (suppI8)
62. Cheung AK: Stages of future technological develop-
ments in haemodialysis. Nephrol Dial Transplant
11:52-58, 1996 (suppI8)
63. Mees EJD: Volaemia and blood pressure in renal
failure: Have old truths been forgotten? Nephrol Dial
Transplant 10:1297-1298,1995