Nephrol Dial Transplant (1996) 11 [Suppl 8]: 10-15
Nephrology
Dialysis
Transplantation
Urea, sodium, and water changes in profiling dialysis
H. Mann and S. Stiller
more permeable to water. Under steady-state conditions there is no great difference in osmolarity between
Control of osmolarity, as well as sodium, urea, and the intracellular (ICV) and extracellular (ECV) comwater balance in anuric patients under intermittent partments. This means that differences in osmolarity
haemodialysis therapy is fundamentally different from between the intra- and the extracellular compartments
subjects with normal kidney function. Whereas in induced by dialysis are very rapidly compensated for
subjects with normal kidney function excretion of by a shift of water. Differences in urea concentration
solutes and water is performed continuously, during are rapidly equilibrated by diffusion of urea. So it is
dialysis, within a short period of time most sodium mainly the change in extracellular sodium concentraand only a small amount of urea are removed convect- tion that has a strong influence on water shift between
ively with the ultrafiltration of water (1 litre of ultrafil- the compartments. Ten millimoles per litre of sodium
trate = 8.5 g sodium chloride and about 1.5 g urea). On chloride =18 mOsmol/l«350 mmHg. Because total
the other hand most urea and a small amount of extracellular osmolarity is more than 90% due to
sodium is removed by diffusion, depending on the sodium and the cellular membrane is nearly imperdialyser clearance and the difference in concentration meable to sodium, changes in osmolarity due to the
elimitation of urea do not cause a shift of water.
between plasma and dialysis fluid.
Therefore osmotic dysequilibrium is mainly induced
The relatively short period of treatment induces by decrease in sodium concentration and not by
acute changes in fluid volume, urea, and sodium con- changes in urea concentration (Figure 2).
centration as well as in plasma osmolarity, which in
healthy subjects never happen. The consequence are
side-effects of dialysis therapy such as osmotic dysequilibrium syndrome, muscle cramps, symptomatic hypo- Transport of urea during dialysis therapy
tension, and thirst.
Having no mechanism to excrete sodium during the Predialysis urea concentration depends on protein
long period between two dialyses, the anuric patient degradation and the distribution volume of urea which
only has the possibility to dilute a high sodium concen- is total body water. Predialysis blood urea concentratration by drinking or to minimize sodium ingestion. tion is usually between 20 and 40 mmol/1. Urea excreConsequently the amount of fluid ingestion depends tion mainly depends on dialyser blood flow. Dialysison the amount of sodium chloride ingestion by eating induced changes in osmolarity due to urea are up to
and probably on an increase in sodium concentration 30 mOsmol/1. Because of its rapid diffusion, there is
due to dialysis treatment itself.
Among other methods profiling of ultrafiltration
Cell Membrane
Cell Membrane
and sodium concentration in dialysis fluid has been
Concentrations [mmol/l]
rel. Permeabilities
proposed to optimize dialysis therapy. To evaluate the
benefit of profiling to the patient the basic conditions
150
Sodium
of water and solute distribution and exchange in
dialysis therapy have to be considered.
Introduction
Water
The physiological properties of the cell membrane
The cell membrane separates the intracellular from the
extracellular fluid compartment and maintains a small
concentration of sodium inside the cell by active transport, whereas sodium concentration in the extracellular
compartment is 30-fold greater (Figure 1). Whereas
the cell membrane is nearly impermeable to sodium it
is 100-fold more permeable to urea and about 1000-fold
Urea
intracellular
extracellular
Fig. 1. Physiological properties of the cell membrane. Left, concentration of urea and sodium in the intracellular and the extracellular
compartment; right, permeability of sodium, water, and urea through
the cell membrane.
© 1996 European Renal Association-European Dialysis and Transplant Association
Urea, sodium, and water changes in profiling dialysis
Convective Sodium Removal
Concentration and
Osmolaritiy Changes
20
i
15
I
- 10
d
o
3
0
r
/
//
f
a
-30
Urea
1
20 mmol/l
Sodium
5 mmol/l
t
j
Corresponding Volume Changes
extracellular
AVolume |
Diffusive Sodium Removal
-40
-
"
"
BV
intracellular
""X
Dialysis Time
Fig. 2. Dialysis-induced changes in ICV and ECV volume by changes
in urea and sodium concentration. Changes in osmolarity by decrease
in plasma urea concentration by 20 mmol/l and by decrease in
sodium concentration by 5 mmol/l (upper part). Change in ICV and
ECV exclusively due to change in sodium concentration: straight
line, urea; dotted line, sodium. As part of ECV blood volume (BV)
is also indicated.
almost no difference in concentration between the ICV
and the ECV and little shift of water between the
compartments. Therefore only extreme changes in
urea concentration could cause side-effects of dialysis therapy, e.g. osmotic dysequilibrium syndrome.
(Figure 2).
Transport of sodium during dialysis therapy
Sodium is mainly excreted by convection. Convective
sodium transport alone does not alter sodium concentration. But there are additional changes in sodium
concentration due to diffusive transport, which depends
on the difference in sodium concentration between
2
3
Ultratillration p]
5
0
1
2
3
4
5
API. Sodium Concentration [mmol/l]
Fig. 3. Amount of dialysis-induced removal of sodium chloride by
convection and by diffusion. Diffusive sodium removed is calculated
for a 65-kg patient, standard dialyser, and Qb = 200 ml/min, Qd
500 ml/min. Ordinate: amount of sodium chloride removed.
blood and dialysing fluid. Diffusive transport may be
positive or negative. Whereas convective sodium transport can more easily be estimated as indicated in
Figure 3, diffusive sodium transport is mostly
unknown. It can be calculated if concentrations of
sodium in blood and dialysis fluid are known or given.
As is shown in Figure 3, at a given difference in sodium
concentration of 5 mmol/l, the diffusive sodium transport during 5 h of dialysis treatment is about 10 g
NaCl [1]. Since the error of sodium concentration
provided by the proportioning unit of the dialysis
machine may be 2% (+3 mmol/l sodium) and the
variation of sodium concentration of the blood also
may be ±2%, the error of sodium gradient between
blood and dialysing fluid may be 6 mmol/l. This
unknown difference in sodium concentration is great
enough to induce side-effects such as osmotic dysequilibrium and the consecutive uncertainty of sodium balance is about 10 g NaCl.
This is also an explanation of why side-effects of
dialysis therapy are inconstant and may vary from one
treatment to another or from dialysis machine to
another because the sodium gradient also varies and
remains unknown.
This problem cannot be overcome by measuring
sodium concentration in blood and dialysing fluid at
the beginning of a dialysis session, because the error
of sodium measurement under optimum conditions is
±1%. Under clinical conditions it is about ±5%
(+7 mmol/l) and the uncertainty of diffusive sodium
transport may amount to 20 g NaCl, when the setting
of dialysis fluid sodium concentration is based on
inaccurate measurements.
So by clinical experience dialysis is best tolerated in
home-dialysis patients using their own proportioning
unit with always the same sodium concentration, with
a constant error of proportioning and conductivity
control, when the patients subconsciously adapt their
salt and fluid intake to present always the same blood
sodium concentration.
Clinical side-effects of dialysis therapy
There are some important side-effects of dialysis
therapy due to change in solutes and osmolarity that
happen in more or less every dialysis unit.
12
Osmotic dysequilibrium syndrome
Osmotic dysequilibrium syndrome is characterized by
headache, increasing nausea, high blood pressure, vomiting, and eventually cerebral cramping. After dialysis
treatment the symptoms need several hours to disappear. As can be shown by continuous telemetric recording of the electroencephalogram, osmotic dysequilibrium occurs when sodium concentration during dialysis decreases by more than 7 mmol/1 (Figure 4). It is
caused by increase of intracranial pressure caused by
fluid shift into the intracellular compartment. There is
no evidence that osmotic dysequilibrium is caused by
excretion of urea [2-5].
Symptomatic hypotension
Symptomatic hypotension is mostly induced when
ultrafiltration exceeds refilling of the intravascular
compartment. It is intensified when simultaneously
fluid shifts to the intracellular compartment because
of decreasing extracellular sodium concentration.
Therefore symptomatic hypotension may also happen
when the so-called dry weight of the patient is not
attained. But not all episodes of symptomatic hypotension during dialysis are caused by change in fluid and
osmolarity. There are also other reasons such as cardiac
arrhythmia or insufficiency of the autonomic nervous
system.
Muscle cramps
Muscle cramps occur mainly towards the end of a
dialysis session. They are more pronounced in patients
who require excessive ultrafiltration. They quickly disappear after injection of some grams of hypertonic
solutes such as sodium chloride or glucose, although
sodium chloride is more effective than glucose or other
substances. Cramps also may happen while the patient
is still fluid overloaded.
Thirst
Thirst is very severe in some patients. It often has its
greatest intensity directly after termination of dialysis
treatment. In some cases dialysis patients drink much
more than ever in their life before. There is no doubt
that thirst is associated with ingestion of salt and rapid
increase in sodium concentration by dialysis [6-8].
Sometimes patients drink much more than necessary
for dilution of increased sodium concentration. A
vicious cycle may develop where the patient overdilutes
his sodium concentration by drinking, and sodium
concentration during dialysis increases, or because of
muscle cramps is even further increased by injections
of hypertonic sodium chloride, which forces him to
drink more. The amount of retained sodium chloride
after bolus injection to treat muscle cramps is mostly
underestimated. In Figures 5 and 6 the absolute and
relative retention of sodium chloride is shown, e.g.
about 78% of the injected sodium at 1 h before the
end of dialysis is retained by the patient.
H. Mann et al.
Profiling as a means of optimizing dialysis therapy
There is no need for profiling of urea, since under
normal conditions side-effects of dialysis treatment are
not caused by urea or by changes in osmolarity due to
urea. To optimize dialysis only ultrafiltration rate and
sodium concentration in dialysis fluid may be altered,
corresponding to a certain profile.
Concerning ultrafiltration, there is much practical
experience that higher rates of ultrafiltration at the
beginning of treatment are better tolerated by patients
than constant ultrafiltration rates throughout the whole
period of treatment. At the end of dialysis there is less
danger of symptomatic hypotension when the ultrafiltration rate is low. In any case the whole amount of
fluid to be removed should be known at the beginning
of the treatment to calculate the profile. Since even
with ultrafiltration-profiled dialysis the ultrafiltration
may exceed vascular refilling, it is better to control
ultrafiltration rate by continuous measurement of circulating blood volume. There are at present several
methods of continuous recording of blood volume
[9-11] and it is also possible to establish a control
system in which ultrafiltration rate is adapted to a
given profile of circulating blood volume. Figure 7
shows the difference between controlled and uncontrolled ultrafiltration: in both cases there is the same
amount of total ultrafiltration. In the case of constant
ultrafiltration rate there is variable blood volume, and
in the case of blood-volume-controlled ultrafiltration
(lower part of the figure) there is variable ultrafiltration. It can be shown that side-effects are lower in
controlled ultrafiltration than in uncontrolled ultrafiltration [12].
Profiling of sodium concentration might be suitable
to shift water from the intracellular to the extracellular
compartement to make it a viable for ultrafiltration,
but it has to be kept in mind that sodium profiling
should not be the cause of sodium ingestion and
subsequent thirst of the patient. So temporary increase
of sodium concentration must be compensated for by
subsequent adequate reduction in sodium concentration.
In Figure 8 there is hourly variation of dialysis fluid
sodium concentration between 160 and 140 mmol/1.
The resulting sodium concentration in blood increases
from 140 to 152 mmol/1. In the case of zero ultrafiltration this is equivalent to ingestion of about 25 g of
sodium chloride to the patient.
Figure 9 shows a balanced sodium profile where the
patient's blood sodium concentration is not changed
by profiling.
Conclusions
Most acute unwanted side-effects of haemodialysis
therapy are induced by ultrafiltration and changes in
osmolarity.
Changes in osmolarity due to elimination of urea
Urea, sodium, and water changes in profiling dialysis
H. Mann et al.
14
Bolus of NaCI During Dialysis
Relative Blood Volume Versus Time
Vb/Vb,s
24.04.90
144
ri
138
136
r—— —
*UFR [ml/mln]
I
T r
12000
I
2.1g
NaCI
2
3
Dialysis Time [h]
Fig. 5. Retention of sodium chloride injected by bolus (20%) for
treatment of muscle cramps. Increase in sodium concentration by
injection of 2 g NaCI 20% at 2 and 3 h after dialysis start. Retained
amount of sodium chloride is 2.1 g.
UFR [ml/mln]
-1-2000
NaCI Added by Bolus During Dialysis
¥1<
•5
14:15
Fig. 7. Difference in blood volume and ultrafiltration rate in controlled and uncontrolled ultrafiltration. Upper part, controlled ultrafiltration. Blood volume follows a predefined curve, whereas
ultrafiltration rate is variable. Lower part, constant ultrafiltration
rate. Blood volume (dotted line) is variable.
80
60
I
40
20:
4[h]
1
Influence of a Sodium Profile
on Plasma Sodium Cone.
16Q
2
3
Dialysis Time [h]
Fig. 6. Percentage of retained amount of sodium chloride injected
by bolus depending on the time of dialysis. All data are calculated
for a patient of 65 kg, blood and dialysate sodium concentration of
140 mmol/1, and standard dialysis data.
have no influence on fluid shift between the extracellular (ECV) and intracellular (ICV) fluid compartments.
Only changes in osmolarity from alterations of
sodium concentration strongly influence fluid distribution between ECV and ICV.
Side-effects such as osmotic dysequilibrium, cramps,
symptomatic hypotension, and thirst are mainly
induced by exchange of sodium.
Profiling dialysis consists in deliberately changing
ultrafiltration and dialysis fluid sodium concentration
in order to avoid side-effects.
Continuous measurement and control of blood
volume seems to be the best method of avoiding
symptomatic hypotension.
Temporary increase of plasma sodium concentration
by profiling induces fluid shift from the ICV to the
ECV. This may facilitate ultrafiltration.
Profiling of sodium should not be the cause of
150
8
8
140
o 130
CO
120,
2
3
4
Dialysis Time [h]
Fig. 8. Influence of a high-sodium profile on patient plasma sodium
concentration calculation for a 65-kg patient: Qb, 200 ml/min; Qd,
500 ml/min. Dotted line, resulting plasma sodium concentration.
positive sodium balance. It only can be recommended
when diffusive sodium balance is comparable to constant sodium concentration in dialysis fluid.
The error in diffusive sodium balance in conventional
haemodialysis varies up to 10 g sodium chloride
per session.
Any intentional change in dialysis fluid sodium
concentration based on sodium measurements under
Urea, sodium, and water changes in profiling dialysis
Influence of a Balanced Sodium
Profile on Plasma Sodium Cone.
160
150
140
i
130
120
2
3
Dialysis Time [h]
Fig. 9. Influence of a balanced sodium profile on patient plasma
sodium concentration.
clinical conditions depends largely on the accuracy of
the measuring device, and may be uncontrollable.
Sodium profiling needs more precise sodium delivery
in dialysis fluid.
The benefits of sodium profiling to the patients have
still to be proved.
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15
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concentration on body fluid distribution during hemodialysis.
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