Review Articles

A Critical Review of Sodium Proling for Hemodialysis

Siegfried Stiller,* Edeltraud Bonnie-Schorn, Aileen Grassmann,
rwer, and Helmut Mann*
Ingrid Uhlenbusch-Ko
*Dialysis Center Aachen and renaSCOPE, Oberusel, Germany

ABSTRACT
In sodium proling, the sodium concentration in the dialysis
uid, instead of being constant, follows a time-dependent
prole over the course of a hemodialysis session. The main aim
of this manipulation is to avoid osmotic disequilibrium by
keeping plasma osmolality in the physiological range. Further
advantages of sodium proling are a reduction in the incidence
of muscle cramps, improved sodium removal, and improved
vascular stability. Many dierent proles have been used by
various investigators. However, if sodium proling is not
appropriately conducted, sodium accumulation with resulting
augmented thirst, increase of interdialytic weight gain, and
hypertension may result. Sodium accumulation may, in fact,

explain the reduced intradialytic morbidity reported in some

short-term sodium proling studies. Randomized, doubleblind studies meeting strict statistical criteria and providing a
careful control to maintain equivalent sodium balances
between the compared treatments are dicult to perform and
have not yet been published. However, because sodium
proling has potential benets, provided that sodium balance
is carefully controlled, it should nevertheless be regarded as a
tool that experienced nephrologists can use for the treatment of
patients who experience intolerable side eects during standard
dialysis.

One task of the dialysis machine is to prepare the

dialysis uid by mixing a concentrate and water to
produce a uid of predened electrolyte concentration. It
has taken years to develop reliable proportioning systems
that keep these concentrations within narrow limits,
especially sodium. The sodium content of dialysis uid
can be varied intentionally during the course of the
dialysis sessiona procedure called sodium proling.
The main aim of sodium proling is to minimize acute
declines in intradialytic plasma osmolality and its
associated symptoms (disequilibrium syndrome). A
second aim of sodium proling is its contribution to
improve plasma relling to help avoid problems associated with the large amounts of ultraltration that are
often necessary to normalize the body uid content of
dialysis patients.
This article reviews the proles used, their consequences regarding plasma sodium concentration, sodium
balance, and shift of body uids, and the clinical results
published to date.

trations are normally closely regulated. Independent

sensors control volume and osmolality; these are linked
via the actions of several hormones to the stimulation of
thirst and the excretion function of healthy kidneys in
order to keep body solute and water contents constant.
For a better understanding, a brief outline of normal
water and electrolyte distributions in the body is
provided.
The total amount of water in the body [total body
water (TBW)] represents about 60% of the adult
human body weight and is distributed between two
main uid compartments. Roughly three-fths of the
TBW is located in the intracellular (IC) space and twofths in the extracellular (EC) space. The EC space
consists of plasma water (7% of TBW), interstitial uid
(19% of TBW), and transcellular uid (2% of TBW)
(see Fig. 1).
The IC and EC uids dier in their electrolyte, protein,
and nonionic substance content (see Table 1) due to the
dierent permeabilities of cell membranes for the various
electrolytes. Remarkable are the great dierences
between the IC and EC concentrations of sodium,
potassium, and chloride: 10 versus 144, 155 versus 4, and
2 versus 100 mmol/L, respectively.
These dierences are mainly induced and maintained
by active carrier systems (Fig. 2). Sodium is the main
cation in the EC space, while chloride and bicarbonate
are the main anions. Only small concentrations of
potassium, calcium, magnesium, phosphate, sulfate,
and organic acid anions are present in this compartment.
Concentration dierences between plasma and interstitial spaces result from the Donnan eect. Potassium is

Electrolyte and Water Physiology

The amount of uid in the various compartments of
the healthy body and the dierent ionic solute concen-

Address correspondence to: Siegfried Stiller, Gruner Weg 8,

52349 Duren, Germany, or e-mail: JS.Stiller@t-online.de.
Seminars in DialysisVol 14, No 5 (SeptemberOctober)
2001 pp. 337347
337

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Stiller et al.

FIG. 1. Fluid compartments in the body. The water distribution

between the dierent compartments in healthy subjects is expressed
as percentages of the total body water (TBW). EC, extracellular;
IC, intracellular. Data from ref. 1.

the main cation found in the IC space, while organic

phosphate and protein are the main anions.
Osmotic equilibrium exists throughout the dierent
uid compartments because of the high hydraulic
permeability of cell membranes. Any change in the
concentration of osmotically active solutes in the EC or
IC spaces results in a passive water ux until osmotic
equilibrium is restored in both compartments. Certain
solutes, most notably urea, do not normally contribute to
these water shifts, as they permeate cell membranes
almost as freely as water. The consequences of a
disturbed salt and water balance are illustrated in Fig. 3.
Sodium and Water Balance
in Dialysis Patients
Sodium and water balance in anuric patients undergoing intermittent hemodialysis therapy is dierent in
principle from subjects with normal kidney function: the
latter excrete solutes and water continuously throughout
the day, while in the former the ingested sodium and

water of up to 3 days must be excreted within the few

hours of a dialysis session. The consequences are sodium
and water changes that never occur in healthy subjects
and the associated occurrence of typical side eects such
as muscle cramps, symptomatic hypotension, thirst, and
osmotic disequilibrium syndrome.
The excess sodium and water accumulated during the
interdialytic interval is primarily stored in the extracellular space, as cells can keep their volume nearly constant
over a longer period of time under physiologic conditions
(5). The two main subcompartments of the EC volume,
that is, the interstitial and intravascular spaces, have
storage capacity for surplus uid.
The plasma concentration and the total body sodium
content in dialysis patients therefore depend on salt and
water ingestion during the interdialytic interval and the
removal during dialysis treatment. Consequently sodium
and water balance in end-stage renal disease (ESRD)
patients can be restored if the individual salt and water
uptake is equal to the amount removed during the
subsequent dialysis session. As sodium easily permeates
dialysis membranes, the sodium concentration of dialysis
uid inuences the plasma sodium concentration and, in
turn, the resulting uid shift between the dierent body
uid compartments during hemodialysis.
Most of the excess sodium is removed by convection
together with the excess water (ultraltration). Pure
ultraltrate is protein-free and contains sodium in almost
the same concentration as in plasma; the ratio of plasma
to ultraltrate sodium is very close to 1 (6). Therefore
140 mmol of sodium is removed per liter of ultraltrate
when the plasma sodium concentration is 140 mmol/L.
However, the ultraltrate does not contain an equivalent
amount of chloride: only 120 mmol/L of chloride and 20
mmol/L anions, most of it bicarbonate, are present.
Consequently about 6.7 g of sodium chloride (NaCl) are
removed per liter of ultraltrate.
Diusive sodium transport depends on the dierence
between the sodium concentration in blood and dialysis

TABLE 1. Concentrations of various ions in the dierent body uid compartments. Values in brackets are concentrations multiplied by
the electric charge, corresponding to meg/L. No ranges are given for the sake of simplicity and to better demonstrate the presence of
electroneutrality in each compartment and iso-osmolality between the compartments. Trace elements are not listed.
Ions

Plasma

Interstitial uid

Intracellular uid

Cations (mmol/L)
Na+
K+
Ca2+
Mg2+

143
4
2.5 (5)
1.0 (2)

144
4
1.25 (2.5)
0.75 (1.5)

10
155
0.001
15 (30)

Sum

150.5 (154)

150 (152)

180 (195)

Anions (mmol/L)
Cl
HCO3
HPO42
SO42
Organic acids
Proteins

103
27
1 (2)
0.5 (1)
5
16

114
30
1 (2)
0.5 (1)
5
*

2
10
50 (100)
10 (20)
0
63

Sum

152.5 (154)

150.5 (152)

135 (195)

Osmolality (mosmol/L)

290

290

290

* The protein concentration in the interstitial uid is low and varies in dierent organ tissues. The anion concentrations of the
intracellular uid may also vary. Adapted from ref. 2.

339

SODIUM PROFILING

FIG. 2. Active and passive transport processes at cell membranes. ATP-requiring carrier systems are responsible for the
existence of concentration gradients for sodium and potassium
between the intra- and extracellular spaces. The cell membrane is
freely permeable to water but nearly impermeable to sodium and is
about 100 times more permeable to potassium. Urea permeates cell
membranes very easily, so that urea levels are equal in the intra(IC) and extracellular (EC) spaces and can rapidly decrease in both
compartments during dialysis. From ref. 3.

Plasma water sodium concentration is 7% greater than

total plasma sodium concentration because of the
volume occupied by plasma proteins. Roughly canceling
this is the eect of negatively charged proteins (mainly
albumin) which cause a small electrical potential dierence across the membrane (negative on the plasma side)
that retards the movement of the positively charged
sodium ions (Donnan eect) (7).
If no signicant amount of sodium is gained or lost
by diusion the dialysis treatment can be called
isonatremic. In order to avoid a diusive loss of
sodium from plasma into the dialysis uid, the dialysis
uid sodium concentration should be approximately
2% higher than the plasma sodium concentration (7).
However, this value varies because the initial sodium
activity and dialysis dynamics (e.g., ultraltration rate,
sodium activity gradient, plasma protein concentration, and pH) dier from patient to patient and from
treatment to treatment, making the isonatric dialysate
sodium concentration dicult to predict (8). Consequently, in one report a dialysis uid sodium concentration averaging 2% lower than the plasma sodium
concentration was necessary to avoid sodium transport
by diusion (8). In clinical practice the sodium
concentration in the dialysis uid is mostly chosen to
be close or equal to the plasma sodium concentration,
althoughas discussed abovethis does not totally
guarantee some diusive sodium loss or gain during
the treatment.
Sodium Proling

FIG. 3. Disturbances in salt and water balance. Disturbances

16 can be caused by water and/or salt decits or excesses; restoration of iso-osmolality between extracellular (EC) space and
intracellular (IC) space is a compensatory process. An iso-osmotic
uid decit in the EC space (1) will only decrease, and an isoosmotic uid surplus (4) will only increase, the EC volume. Water
loss from the EC space (2) will lead to compensatory water shift
() from the IC to the EC space and a pure water gain (6) from the
EC to the IC space. A salt loss from the EC space (3) will lead to a
compensatory water shift from the EC to the IC space, and a salt
gain in the EC will result in a water shift from the IC to the EC
compartment. Data from ref. 4.

uid. By denition, it is exactly dependent on the sodium

activity in both uid streams. Not all the sodium ions
present are available to diuse through the dialysis
membrane (due to binding to proteins and other anions).
In dialysis uid, sodium activity is approximately 97% of
its concentration, but plasma sodium activity is approximately equal to its concentration due to two opposing
eects associated with the presence of plasma proteins.

In sodium proling the sodium content of the dialysis

uid is varied during the course of the dialysis treatment
in order to actively inuence plasma sodium levels.
Independent of the time course of a prole, an important
consideration is its inuence on the postdialysis plasma
sodium concentration; this results from diusive sodium
transport during the treatment and represents the
respective diusive sodium balance. The latter can be
either neutral (``balanced''), positive, or negative:
1. Sodium balance neutral: the prole is neutral with
respect to the diusive sodium balance. At the end
of the session neither plasma osmolarity nor uid
distribution between the IC and EC space is
changed.
2. Sodium balance positive: the prole enhances
plasma sodium levels. Plasma osmolarity is increased and uid is shifted from the IC to the EC
space.
3. Sodium balance negative: the prole leads to
diusive sodium loss. Plasma osmolarity is then
decreased, and uid is shifted from the IC to the
EC space.
The aim of sodium proling is to prevent osmotic
disequilibrium, which is responsible for a variety of
central nervous system disturbances during dialysis, and
to support plasma relling, and in this way to possibly
reduce the incidence of intradialytic hypotension.
The intradialytic decline in eective plasma osmolality is primarily due to plasma sodium loss. However,

340

Stiller et al.

reduction in plasma osmolality can be minimized by

modifying the sodium concentration in the dialysis
uid according to the patient's plasma sodium concentration. Sodium concentrations in dialysis uid that
are equal to or higher than those in the plasma
prevent a decline in extracellular osmolality and inhibit
intracellular water uptake (which predisposes the
patient to disequilibrium).
In addition to this, dialysis uid sodium concentrations can be selected not only to prevent intracellular
water uptake but also to support water transport into the
extracellular space, that is, to support plasma relling
(914). However, the eect of sodium proling on
preserving EC volume is small compared to the volume
depletion caused by ultraltration (11,15). For example,
a 1 mmol/L increase in the concentration of sodium in
the EC compartment (volume of approximately 10 L)
expands the EC space by 1.3% (130 ml) and the
intravascular compartment by only 30 ml. Consequently
a 5 mmol increase in the EC sodium concentration results
in an intravascular uid gain of only 150 ml. This is small
compared to the blood volume loss of approximately
6001000 ml generally caused per session by ultraltration (200300 ml/L ultraltrate) (11).
However, the negative consequences of high dialysis
uid sodium concentrations must also be taken into
consideration (16)the resulting sodium accumulation
in the patient frequently augments postdialysis thirst,
increases interdialytic weight gain, and favors the
development of hypertension. Such eects have also
been observed with the frequent use of hypertonic or
isotonic salt infusions following the occurrence of
hypotension. Sodium proling was developed to achieve
the benets of high plasma sodium levels (i.e., avoidance
of disequilibrium syndrome and support of plasma
relling) while simultaneously avoiding unnecessary
high, intradialytic sodium uptake by the patient with
the associated risk of sodium loading.
What Must Be Considered in Conducting
Sodium Proling?
Generally sodium proling can only be eective when
a measurable change in the plasma sodium concentration, within a physiologically safe range, is provoked by
the proling. This can only be achieved if the dierence
between the concentration of plasma sodium and dialysis
uid sodium (sodium diusive gradient) exceeds that
necessary for isonatremic dialysis.
The maximum possible change in plasma sodium
levels by proling should be limited to approximately 45
mmol/L. (Fresenius machines have a maximum dialysis
uid sodium concentration of 151 mmol/L for physiologic and technical reasons.) Furthermore, sodium
proling is only advantageous for the patient in the long
term if it results in a neutral sodium balance. An
unbalanced high dialysis uid sodium prole results in a
signicant increase in postdialysis plasma sodium and
consequently in sodium accumulation, as shown in
Fig. 4a. A balanced sodium prole, such as that depicted
in Fig. 4b, leads to a physiologic postdialysis plasma
sodium concentration (17).

FIG. 4. Alternating dialysis uid sodium (Na+) prole ()

and the induced change in plasma sodium concentration (- - -).
(a) Unbalanced prole leading to augmented sodium levels in the
patient; (b) balanced alternating proling. Adapted from ref. 17.

How and with What Result Has Sodium

Proling Been Performed in the
Clinical Setting?
A wide variety of sodium proles (i.e., decreasing,
increasing, and alternating) and diverse prole forms
(e.g., linear, stepwise, and exponential) have been used
for dierent clinical situations. The results of some major
studies on sodium proling were reviewed in detail in a
previous work (3); Table 2 provides an overview of these
results. The inuence of the dierent prole types and
forms on vascular instability, disequilibrium syndrome,
and the clinical signs of sodium accumulation (i.e., thirst,
intradialytic weight gain, and hypertension) are described, insofar as these were investigated.
Decreasing sodium proles were mostly employed.
Here advantage is taken of the positive eects of high
dialysis uid sodium concentrations on plasma osmolality and plasma relling at the beginning of the
treatment, when ultraltration is best tolerated. Indeed,
ultraltration may even be enhanced in this phase, as in
the case of simultaneous ultraltration proling. Alternating hyper-/hyponatremic dialysis uid sodium proles were proposed in the early 1980s; the aim was the
induction of an alternating uid shift across the cellular
membrane to improve the transport of uremic toxins out
of the cell by solvent drag (35). The incidence of
disequilibrium syndrome was found to be reduced
with the use of such proles (reviewed in refs. 24 and
28). Increasing sodium proles were less commonly

19

15

39

15

10

21

22a,b

23

13

14

24

20

10

18

a,b

Reference

150

130

160

138

140

e.g.,
142

138

e.g.,
141

190

150

From

Individualized

Individualized

137

140

146

149

e.g.,
137

146

e.g.,
137

140

130

To

Dialysis uid sodium

(mmol/L) and form of prole

140

141

138

140

e.g.,
140

138

140

146

140

Compared
to xed

Cramps

Cramps

Weight gain
Predial. bloodpressure
Pre- and postdial. serum
sodium

Thirst
Weight gain
Predial. blood pressure
Size of left ventricle

Cramps
Loss of osmolality

9 weeks

1 HD-session

5 days

Upto 6 months

6 weeks

Weight gain Postdial.

serum sodium

1 HD-session

1 HD-session

Postdial. serum sodium 1 week

No dierence between the 3 prole forms

Cramps

Intradial. hypotension
Early decrease of
Blood volume reduction
osmolality
Heart rate
Use of mannitol and saline

Blood volume reduction

Intradial. hypotension
Heart rate

Intradial. hypotension
Blood volume reduction
Plasma relling

Intradial. hypotension
Intradial. saline

Follow up period

Weight gain
14 days
Predial. blood pressure

Eect on
Signs of sodium
disequilibrium syndrome accumulation

Intradial. hypotension
Cramps
Increase of HR
Headache
Variation of cardiac output

Blood volume reduction

Plasma relling
Intradial. hypotension

Intradial. hypotension
Intradial. saline
Increase of HR

Intradial. hypotension
Use of mannitol

Intradial. hypotension

Eect on
cardiovascular system

TABLE 2. Clinical results of sodium proling

SODIUM PROFILING

341

16

11

12

22

16

19

18

25

12a

4a

27

28c

9a

29a

26

Reference

155

160

e.g.,
144

160
155

137

150

e.g.,
151

148

From

Individualized

Individualized

135

140

e.g.,
138

140

128

140

e.g.,
134

138

To

Dialysis uid sodium

(mmol/L) and form of prole

140

140

142

140

137

140

140

138

Compared
to xed
Cramps
(best linear prof.)
Headache
(only linear and
stepped prof.)
Nausea
Loss of osmolality

Intradial. hypotension
use of saline
Postdial-standing blood
pressure

Plasma volume reduction

Intradialytic hypotension
(stepped prole had better
eect in early, linear in
late dialysis)

Intradial. hypotension

Intradial. hypotension

Intradial. hypotension
Blood volume reduction

Intradial. hypotension
Plasma relling

Blood volume reduction

Intradial. hypotension

Cramps
Headache
Nausea

Cramps
Headache
Nausea

Anorexia

2 weeks

1 HD-session

2 weeks

8 weeks

Follow up period

Weight gain
Dry weight
Antihypertensive
medication

Sodium retention

3.5 months

1 HD-session

Weight gain
4 months
Predial. blood pressure

Thirst Weight gain

36 months
Predial. blood pressure

Thirst
Weight gain
Postdial. sodium

Sodium mass
balance

Thirst
(only stepped
prof.)

Eect on
Signs of sodium
disequilibrium syndrome accumulation

Postdial. fatigue and dizziness

Intradial. hypotension
Use of saline
Postdial. hypotension
(stepped prof. was best)

Eect on
cardiovascular system

TABLE 2. Continued

342
Stiller et al.

Individualized
computer
assisted

Equal sodium balance

between proled
and standard HD

e.g.,
?

10%
more
than
target Individ.
computer
value
assisted

e.g.,
?

155

160

e.g.,
?

10%
below
target
value

e.g.,
?

140

Individ.

140

138

140

141

Cramps
Headache
Nausea
Vomitting

Stroke volume reduction

Intradialytic hypotension

Intradial. hypotension

Blood volume reduction

Cardiac output reduction
Stroke volume reduction
Heart rate
Intradialytic blood pressure
reduction

Cramps

No dierence between the 2 prole forms

Intradial. hypotension

Blood volume reduction

Intradial. hypotension
Heart rate

, increased; , decreased; , no change; ? information not available from publication; n, number of patients.
Studies including ultralteration proling.
b
Studies using computerized programs for individualized sodium proling.
c
Studies including biofeedback technology.

34b

33c

32

11

23

31

10

30b

4 weeks

Sodium balance
Mean arterial sodium

4 HD-sessions

4 HD-sessions

2 HD-sesions
Sodium balance by
individualized procedures
(computer assisted)

Thirst Weight gain

Fatigue Hypertensive
episodes

1 HD-session
Sodium balance by
individualized procedures
(computer assisted)

SODIUM PROFILING

343

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Stiller et al.

employed; they were used to preserve the plasma volume

during the last period of dialysis in cases where the
ultraltration is still high. These have been reported to be
especially benecial in reducing the incidence of muscle
cramps (13,21), probably because of reduced sodium
removal (28).
The eect of linear (9,23,25,31), stepwise (2,23,25,31),
and exponential (23,25) prole forms have also been
examined in some studies. Postdialysis hypotension (23)
and early intradialytic hypotension (11) were best attenuated by decreasing, stepped proles; linear proles
sometimes reduced muscle cramps (25) and late intradialytic hypotension (11). However, such eects were not
observed in other studies (23,31).
Patients of various ages have been studied: sodium
proling reduced dialysis-related symptoms in two
children, but was associated with an increase in predialysis blood pressure and interdialytic weight gain (19);
proling was found to be mostly advantageous in young
adults (25) and in geriatric patients (9).
Studies of sodium proling published to date (see
Table 2) have three important weak points. First, the
overall patient numbers and the numbers of dierent
patient subgroups (age, comorbid factors) studied were
often small. Second, details of the dierent proles
applied varied considerably. Such details were the
concentrations of sodium used in the dialysis uid; the
proling type, that is, alternating, increasing, or decreasing; the proling form, for example, linear, stepwise, or
exponential; and the constant sodium levels with which
the proles are compared. An appropriate comparison of
sodium proles with standard dialysis (or with dierent
proles) requires that patients lose the same amount of
sodium with each treatment mode. This diculty is
further complicated by the fact that patients do not have
the same baseline plasma water sodium concentration
and often require dierent ultraltration amounts
(reviewed in ref. 36). The consequence is uncertainty
about whether the clinical ndings reect the application
of a specic prole, or whether they are simply the result

of dierences in absolute sodium removal (example

discussed in ref. 37). Third, from Table 2 it is apparent
that the majority (9,12,13,18,19,21,2325,27,31,33,
3841) of proles used (17 of 23) add sodium by
diusion. They thus increase plasma sodium concentration during dialysis; this may partly explain the reported
short-term benets.
What Are the Potential Benets and Risks
of Sodium Proling?
The results from the 22 studies cited in Table 2 are
summarized in Table 3, independent of the proling
form, type, and level. A reduced incidence of clinical
symptoms associated with intradialytic osmotic disequilibrium was found in nine of the studies. However, in two
of these studies muscle cramps but not other important
clinical symptoms, such as nausea and hypotension, were
inuenced. Less vascular instability was observed in 14
studies, but was not observed in 8 studies.
With regard to the possibility of proling causing
sodium accumulation, it is worth noting that there was
no follow-up of predialysis and/or postdialysis sodium
levels or of clinical signs of sodium accumulation in six of
the studies (12, 2022, 24,33). Clinical or laboratory signs
of sodium accumulation were found in eight studies
(9,13,19,23,25,27,29,31) but not in the other eight cases
(4,14,18,26,28,30,32,34). In one of these investigations
(4), a decreasing sodium prole reduced serum sodium
levels to normal or even hyponatremic values and led to a
decrease in thirst and interdialytic weight gain. Some
investigations (e.g., refs. 9 and 25) found sodium proling
to be benecial for the majority of patients, while others
concluded that it was only clearly benecial for a small
group of patients (e.g., 22% in ref. 31) identiable only by
trial and error. All reports focused on potential shortterm eects; data regarding long-term consequences of
sodium proling are not yet available (45).
In summary, the eects of sodium proling on osmotic
disequilibrium and on vascular instability appear to be

TABLE 3. Reported risks and benets of sodium proling

Reported benets

Reported risks

Reduced incidence of intradialytic osmotic disequilibrium (nausea, headache, cramps)

Yes: 13 (cramps), 18 (cramps), 31 (cramps), 2123, 25, 27, 33
No: 13 (headache, nausea), 31 (headache, nausea)

Increase in predialysis sodium concentration

Yes: 10, 19, 23
No: 27, 2931

Reduced incidence of vascular instability syndrome

Yes: 9, 13, 1823, 26, 28, 3133, 36
No: 4, 12, 14, 24, 27, 29, 30, 34

Thirst
Yes: 25, 31 (stepwise decreasing prole), 27
No: 25 (linear, exponentially decreasing prole)

Optimal individual sodium removal and sodium balance

Yes: 10, 28, 33, 42
No: 9, 19, 23

Increase in interdialytic weight gain

Yes: 19, 31
No: 18, 23, 27, 29

Less saline administration during HD

Yes: 10, 20, 23, 25
No: 29

Hypertension
Yes: 19, 31
No: 18, 23, 27, 29

Assistance in the prevention of hypotensive episodes in conjunction with

ultraltration proling
Yes: 11, 13, 20, 22, 24, 26, 39, 43, 44
No:

Decrease in cardiac performance

Yes: 19 (left ventricular dilatation)
No: 34

Study results are summarized irrespective of the particular proles used (see Table 2 for details of the proles). Benets mostly resulted
from modulation of intradialytic sodium removal; risks are the consequences of sodium accumulation.

SODIUM PROFILING

promising. However, attention should be focused on the

likelihood that sodium accumulation may account for
some of the observed benets, as high sodium proles
were applied in the vast majority of cases; this aspect was
often neglected.
Sodium proling may, if done correctly, preserve the
benets of higher dialysis uid sodium concentrations
and avoid the risks of sodium accumulationthis is of
particular relevance for hypotension-prone patients. The
incidence of osmotic disequilibrium syndrome, vascular
instability syndrome, and the need for intradialytic saline
administration can potentially be reduced. In addition,
sodium proling may be employed to optimize the
individual sodium removal. Sodium proling may be
particularly useful in preventing hypotensive episodes
when used in conjunction with ultraltration proling:
high dialysis uid sodium concentrations should be
employed when the ultraltration rates are high. Risks of
sodium proling emerge from the danger of sodium
accumulation, with subsequent thirst, augmented interdialytic weight gain, and hypertension.

345

Evidence of the blood pressure stabilizing eect of ultraltration proling alone and in combination with sodium
proling has already been published (10,16,40,55,56), but
long-term benets of proled dialysis have yet to be
established.
An example of a clinical application of combined
ultraltration and sodium proling is given in Fig. 5.
Combined proling resulted in improved blood pressure
stability without increasing the postdialysis sodium
levelbenets that have been conrmed in many studies
(e.g., refs. 1013,20,22,38,40). A reduction in the need for
antihypertensive medication has also been reported (29).
In summary, combined ultraltration and sodium
proling may be a further step toward an optimal,
individualized dialysis therapy, especially for hypotension prone patients. Both proles have to be chosen for
the individual patient according to the particular water
and sodium balances required, and must take intra- and
postdialysis symptoms into account. High dialysis uid
sodium concentrations are recommended in combination with high ultraltration rates (and vice versa),
an approach that optimizes plasma relling when

What New Developments Support

Sodium Proling?
Accurate sodium proling requires the ability to
predict the nal plasma sodium concentration provoked
by a particular prole, as well as techniques to accurately
follow the changes in plasma sodium levels during the
session. Mathematical models are available for these
predictions (e.g., 32,4547). Techniques for on-line
determination of sodium ux between dialysis uid and
plasma during dialysis (48) are also available. Some are
based on the positioning of two ion selective electrodes in
a ow-through cell; this is coupled with a microprocessor
controlled hydraulic unit that continuously pumps a
small amount of dialysis uid through the cell. Determination of plasma sodium concentrations based on
dialysis uid conductivity measurements has also been
reported (26,28,33,42,49). These noninvasive techniques
allow automatic optimization of dialysis uid sodium
concentration and may, in the future, permit an exact
removal of accumulated water and sodiumindividual
postdialysis dry weights and plasma water conductivities
will be prescribed by the physician (28,32,33,42,49).
Existing systems for monitoring sodium removal
during treatment (50), computerized sodium balancing
and modeling (10,28,30,42,46,51,52), and biofeedback
technology must be integrated into more and precise
studies.
Combined Ultraltration and Sodium Proling
Ultraltration proling has been shown to be successful (much more than sodium proling) in alleviating
intradialytic complications due to hypovolemia (e.g.,
hypotension). It also does not carry the risk of a high
postdialysis plasma sodium concentration (11,53,54).
Dialysis machines capable of performing combinations
of both ultraltration and sodium proling using sodium
balancing are available and gaining acceptance (11,55).

FIG. 5. Comparison between standard and computer proled

dialysis: modication of (a) ultraltration rate and dialysis uid
sodium concentration, (b) plasma volume, and (c) serum osmolality. During standard dialysis ultraltration rate (UFR) was
1 L/hr and the dialysis uid contained 143 mmol/L sodium. During
computer modulated dialysis the UFR was 1.4 L/hr during the rst
30 minutes, and was stepwise reduced to 0.2 L/hr during the last
30 minutes; the dialysis uid sodium concentration in the special
prole shown here started at 134 mmol/L, reached a maximum of
150 mmol/L at 1.01.5 hours, and decreased to 135 mmol/L at the
end. Adapted from ref. 44.

346

Stiller et al.

ultraltration-induced plasma volume (PV) reductions

are highest. Combined proling should not be employed
as a tool to shorten dialysis time, but should be seen as an
approach to reducing intradialytic morbidity during
sessions of adequate length while avoiding sodium
accumulation in the patient. Some monitoring methods
for blood volume and plasma sodium concentration
during dialysis are already available (e.g., continuous
blood volume monitors and on-line plasma sodium
monitors), while others are subjects of on-going research.
Conclusion
Many of the benets of sodium proling that have
been claimed in the literature have not yet been fully
proven. Some of the reported benets can be attributed
to the use of high-sodium proles which increase serum
sodium concentration during dialysis. Many studies were
of insucient length (less than 2 weeks) to allow
conclusions to be drawn about the long-term eects of
sodium proling. Randomized, double-blind studies
meeting strict statistical criteria and a careful control of
sodium balances between the compared treatments are
dicult to perform and have not yet been published.
The future of sodium proling is promising. Techniques to accurately follow the changes in plasma sodium
levels during the session, measure sodium ux between
dialysis uid and plasma on-line during dialysis, as well as
the application of existing mathematical algorithms for
the prediction of the postdialysis plasma sodium levels
provoked by proling are available or on the horizon
for clinical use. They will make sodium proling
more reliable in avoiding sodium accumulation. Modern
dialysis machines oer the possibility of choosing
between dierent predened proles and facilitate the
conduction of balanced neutral sodium proles by partial
integration of the above mentioned new techniques.
Results of a recent questionnaire reveal that 26% of
2400 international nephrologists were in favor of sodium
proling for all patients, 33% for patients with excessive
weight gains, and 38% for only a few selected patients
(53). This reects a considerable interest in sodium
proling, perhaps as a medium to achieve dry weight
during a symptom-free or almost symptom-free dialysis
withoutand this is the most important point
inducing a positive sodium balance. However, because
of the remaining risks and the still unsatised need for
comprehensive and precise studies supporting sodium
proling, this technique should currently be regarded as a
tool for nephrologists treating patients who experience
intolerable side eects during standard dialysis.
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