The role of glucocorticoids in sodium retention in cirrhotic patients: a double blind, randomized, crossover study


Højmark Hansen, M.; Kristensen, S.Skott.; Schaffalitzky de Muckadell, O.B.; Thiesson, H.Charlotte.; Andrew, R.; Dam Fialla, A.

Scandinavian Journal of Gastroenterology 47(8-9): 1030-1036

2013


Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol--by activation of the mineralocorticoid receptor--may contribute to the abnormal sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone--placebo) increased 55.1 (-26.4-168.7) mmol/day (median and range). No statistically significant differences (dexamethasone--placebo) were found in changes in body weight (0.00 (-0.45-2.20) kg/day), diuresis (0.56 (-0.35-1.43) L/day) or mean arterial pressure (8.33 (-16.0-41.3) mmHg) (median and range) in reference to the preceding 24 h basal period. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver.

Scandinavian
Journal
of
Gastroenterology.
2012;
47:
1030-1036
informa
healthcare
ORIGINAL
ARTICLE
The role
of
glucocorticoids
in
sodium
retention
in
cirrhotic
patients:
A
double
blind,
randomized,
crossover
study
MARTIN
HOJMARK
HANSEN
1
'
3
,
STEFFEN
SKOTT
KRISTENSEN
1
'
3
,
OVE
B.
SCHAFFALITZKY
DE
MUCKADELL
1
'
3
,
HELLE
CHARLOTTE
THIESSON
2
'
3
,
RUTH
ANDREW
4
&
ANNETTE
DAM
FIALLA
1
1
Department
of
Medical
Gastroenterology,
Odense
University
Hospital,
Odense
C,
Denmark,
2
Department
of
Medical
Nephrology,
Odense
University
Hospital,
Odense
C,
Denmark,
3
University
of
Southern
Denmark,
Odense
M,
Denmark,
and
4
Queen's
Medical
Research
Institute,
University
of
Edinburgh, Edinburgh,
UK
Abstract
Objective.
Cirrhotic
patients
have
an
increased
ratio
of
urinary
cortisol
to
cortisone
metabolites,
indicating
decreased
renal
11-13-hydroxysteroid
dehydrogenase
type-2
activity.
This
suggests
that
cortisol
by
activation
of
the
mineralocorticoid
receptor
may
contribute
to
the
abnormal
sodium
retention
evident
in
cirrhosis.
The
aim
was
to
elucidate
the
role
of
glucocorticoids
in
sodium
retention
in
decompensated
cirrhotic
patients.
Methods.
A
randomized,
double-blind,
placebo-
controlled,
crossover
study
was
performed
in
nine
patients
with
alcoholic
cirrhosis
of
the
liver.
A
washout
interval
of
14
days
separated
the
two
periods.
After
a
basal
period
of
36
h,
dexamethasone
(0.5
mg
every
6
h)
or
placebo
was
given
for
two
days.
Urine
was
collected
for
12
h
periods,
and
the
concentrations
of
sodium,
potassium,
creatinine,
cortisol
and
cortisol
metabolites
were
determined.
Blood
samples
for
hemoglobin,
glucose,
sodium,
potassium,
creatinine,
aldosterone
and
cortisol
were
obtained
daily.
Results.
Dexamethasone
treatment
decreased
S-cortisol
92.3%
(82.9-93.4%)
(median
and
range)
compared
with
that
in
the
basal
period.
Natriuresis
(dexamethasone
placebo)
increased
55.1
(-26.4-168.7)
mmol/day
(median
and
range).
No
statistically
significant
differences
(dexamethasone
placebo)
were
found
in
changes
in
body
weight
(0.00
(-0.45-
2.20)
kg/day),
diuresis
(0.56
(-0.35-1.43)
L/day)
or
mean
arterial
pressure
(8.33
(-16.0-41.3)
mmHg)
(median
and
range)
in
reference
to
the
preceding
24
h
basal
period.
Conclusion.
These
results
indicate
that
endogenous
glucocorticoids
contribute
to
the
sodium
retention
in
patients
with
alcoholic
cirrhosis
of
the
liver.
Key
Words:
11-13-hydroxysteroid
dehydrogenase
type
2,
cirrhosis,
cortisol,
liver,
mineralocorticoid
receptor,
sodium
retention
Introduction
The
prognosis
of
liver
cirrhosis
is
poor,
and
is
characterized
by
increased
morbidity
and
mor-
tality,
with
a
10-year
relative
survival
of
34%
[1].
Survival
rate
is
lower
if
complications
such
as
ascites,
variceal
bleeding
or
encephalopathy
are
present
at
the
time
of
diagnosis
[2]
.
A
better
under-
standing
of
the
pathophysiology
leading
to
complica-
tions
may
lead
to
an
adequate
and
improved
treatment
[3].
According
to
the
forward
theory
of
ascites
formation,
a
relative
underfill
of
the
central
vascular
compartment
increases
the
activity
of
renin-angiotensin-aldosterone-
system
(RAAS)
and
other
anti-natriuretic
systems.
This
leads
to
increased
water
and
sodium
retention
causing
plasma
volume
expansion
leading
to
ascites
formation
[4].
In
addition
a
forward
increase
in
splanchnic
cap-
illary
pressure
leads
to
increased
lymph
production
which
contributes
to
the
ascites
formation
[3,5].
How-
ever,
not
all
cirrhotic
patients
have
increased
levels
of
aldosterone
when
accumulating
ascites
[6].
Correspondence:
Ove
B.
Schaffalitzky
de
Muckadell,
Afdeling
for
Medicinske
Mavetarmsygdomme
S,
Odense
Universitetshospital,
Sdr.
Boulevard
29,
5000
Odense
C,
Denmark.
E-mail:
sdm@ouh.regionsyddanmark.cik
Martin
Hejmark
Hansen
and
Steffen
Skott
Kristensen
contributed
equally.
(Received
27
February
2012;
revised
18
April
2012;
accepted
16
April
2012)
ISSN
0036-5521
print/ISSN
1502-7708
online
©
2012
Informa
Healthcare
DOI:
10.3109/00365521.2012.690044
Contacted:
37
{
Excluded:
175
J
Declined:
25
V
[
Accepted:
12
J
Excluded:
3
2
due
to
previously
unknown
diabetes
1
lost
to
follow
up
Glucocorticoids
and
sodium
retention
1031
E
'N
Total
number
of
cases:
212
Completed:
9
Figure
1.
Screening
process.
Aldosterone
is
a
steroid
hormone
which
acts
on
the
nuclear
mineralocorticoid
receptor
(MR),
thus
lead-
ing
to
an
increased
synthesis
of
a
number
of
proteins.
Most
important
is
the
epithelial
sodium
channel
(ENaC),
which
increases
sodium
reabsorption
in
the
distal
tubule
and
the
collecting
ducts.
This
leads
to
an
osmotic
gradient
across
the
epithelium,
which
in
turn
causes water
to
be
reabsorbed
[7].
Cortisol
is
another
steroid
hormone
produced
in
the
adrenal
glands.
Chemically
cortisol
resembles
aldosterone
and
is
able
to
act
on
the
MR.
Further-
more,
the
affinity
of
cortisol
to
the
MR
is
similar
to
that
of
aldosterone
but
cortisol
exists
in
a
100-1000
times
higher
concentration
in
plasma.
The
selective
access
of
aldosterone
to
MR
is
ensured
by
the
enzyme
11-P-hydroxysteroid
dehydrogenase
type
2
(11-1i-
HSD2),
which
converts
cortisol
into
the
inactive
metabolite,
cortisone,
and
thus
protects
MR
from
activation
mediated
by
cortisol
[8,9].
In
patients
lack-
ing
active
11HSD2,
inappropriate
occupation
of
MR
by
cortisol
can
be
attenuated
by
administration
of
dexamethasone,
a
synthetic
glucocorticoid
drug
[8].
Dexamethasone
has
low
affinity
to
the
MR
[10]
but
exerts
negative
feedback
effects
on
the
hypothalamic-
pituitary-adrenal
axis
via
the
glucocorticoid
receptor,
reducing
the
production
of
cortisol
[11].
The
renal
glucocorticoid-metabolizing
enzyme
11-1i-HSD2
is
downregulated
in
bile
duct-ligated
cirrhotic
rats
and
it
has
recently
been
shown
that
cirrhotic
patients
have
an
increased
ratio
of
urinary
cortisol
to
cortisone
metabolites,
indicating
decreased
renal
11-1i-HSD2
activity
(unpublished
observa-
tions).
Furthermore,
it
has
been
demonstrated
that
in
bile
duct-ligated
rats,
urinary
sodium
excretion
level
increased
when
the
rats
were
treated
with
dexa-
methasone
[12].
These
findings
suggests
that
corti-
sol
by
activation
of
MR
may
play
a
role
in
the
abnormal
sodium
retention
evident
in
cirrhosis.
The
aim
of
this
study
was
to
elucidate
the
role
of
glucocorticoids
in
sodium
retention
in
decompen-
sated
cirrhotic
patients.
Methods
Screening
process
The
study
was
performed
according
to
the
Declara-
tion
of
Helsinki
and
approved
by
the
local
ethics
committee
(VF20040245).
The
participants
were
recruited
from
among
patients
with
alcoholic
liver
cirrhosis
from
the
Department
of
Medical
Gastroen-
terology
at
Odense
University
Hospital.
The
patients
were
either
seen
in
the
outpatient
clinic
in
the
period
January
2010—July
2011
and
identified
by
the
ICD-10
diagnostic
code
K70.3,
cirrhosis
hepatitis
Day
1
Check
in
Day
2
Blood
samples
12
h
urine
Day
2
Blood
samples
12
h
urine
Adm.
capsule
Day
4
Blood
samples
12
h
urine
Adm.
capsule
Day
5
Blood
samples
12
h
urine
Adm.
capsule
Figure
2.
This
figure
demonstrates
the
main
events
in
a
study
period.
For
detailed
description
see
the
Method
section.
1032
M.
H.
Hansen
et
al.
Table
I.
Patient
characteristics.
Baseline
equals
the
basal
period
from
the
first
admission
regardless
of
treatment.
Baseline
Number
of
participants
N
9
Age
Years
56
(43-68)
Male/Female
N
8/1
B-Hgb
mmol/L
8.2
(5.35-9.55)
INR
/U
1.3
(1-1.9)
P-Albumin
gIL
33
(28-49)
P-Bilirubin
µmon
22
(10-115)
P-Na
mmol/L
138.5
(126-141.5)
P-K
mmol/L
3.85
(2.95-4.65)
P-Creatinine
µmon
83.5
(54.5-132.5)
Child
Pugh
Score
(A/B/C)
N
2/6/1
MELD
Score
Points
8
(0-16)
Ascites
Yes/No
N
7/2
Heart
Rate
BeatsImin
70.3
(57.33-93.67)
Sodium
excretion
mmol/day
142.5
(12.14-282.9)
Diuretics
Yes/No
N
8/1
Spironolactone
Yes/No
N
7/2
Furosemide
Yes/No
N
7/2
Amiloride
Yes/No
N
1/8
alcoholica,
or
as
inpatients
in
the
periods,
February—
April
and
August—October
2011.
In
total,
212
patients
were
screened
through
a
systematic
review
of
patient
files.
Only
37
patients
were
eligible
and
contacted
as
possible
participants
(Figure
1).
Inclusion
criteria
were
patients
with
alcoholic
liver
cirrhosis
and
age
above
18
with
presence
of
ascites
or
diuretic
treatment
due
to
ascites.
Exclusion
criteria
were
diagnosed
diabetes
mellitus,
suspicion
of
hyper-
corticism,
transjugular
intrahepatic
portosystemic
1
00-
50-
0
N
E
c
o
0
E
.E
E
-50
c
a)
rn
ca
.c
—1
00-
shunt,
dialysis
due
to
renal
insufficiency,
abdominal
cancers,
or
non
cooperation.
Patients
who
fulfilled
the
criteria
were
given
verbal
and
written
information
about
the
study
design
and
the
participant's
written
consent
was
obtained.
An
abdominal
ultrasound
examination
was
subsequently
performed
in
order
to
verify
the
presence
of
ascites.
Study
design
The
study
was
a
randomized
double-blind
crossover
design.
A
washout
interval
of
fourteen
days
separated
the
periods.
Each
period
consisted
of
five
days
(Figure
2).
On
day
1,
height
and
blood
pressure
were
measured.
On
day
3,
after
a
basal
period
of
36
h,
the
patient
was
given
either
dexamethasone
or
a
placebo.
The
tablets
were
encapsulated
in
white
opaque
capsules
to
secure
double
blinding.
One
cap-
sule
was
administered
every
6
h
until
day
5
at
2
a.m.
The
patients
were
randomized
to
receive
dexameth-
asone
or
placebo
in
period
one,
and
thus
placebo
or
dexamethasone
in
period
two.
Patients
were
instructed
to
attempt
identical
sodium
intake,
using
diet
sheets,
in
the
two
periods.
Intake
of
fluid
was
standardized
to
2
L.
During
both
periods
the
patients
received
their
normal
daily
med-
icine,
which
was
identical
in
the
two
periods.
The
patient
was
weighed
every
morning
at
8
a.m.
using
an
electronic
scale.
The
blood
pressure
and
heart
rate
were
measured
two
times
a
day,
at
8
a.
m.
and
8
p.m.
using
an
electronic
blood
pressure
monitor.
Urine
collection
Urine
was
collected
into
12
h
samples.
The
volume
was
determined
by
weight
measurement.
The
urine
600
-
450
-
300
-
150
-
S-
Cor
t
iso
l
(nmo
VL)
0
—150-
Placebo
Dexamethasone
0
1
2
3
4
5
Measurements
(nr)
Figure
3.
Change
in
urinary
sodium
excretion
in
the
placebo
and
dexamethasone
period
(p
<
0.05,
n
=
9).
Figure
4.
Median
cortisol
levels
during
the
placebo
(,)
and
dexamethasone
( )
period
(p
<
0.05,
n
=
9).
Glucocorticoids
and
sodium
retention
1033
So
d
iu
m
ina
t
ke
(mmo
l
/day
)
300
250
200
-
1
150
100
5
0
0-
1
2
3
4
5
Patients
7
8
9
Figure
5.
Sodium
intake.
Individual
sodium
intake
in
the
placebo
(0)
and
the
dexamethasone
( )
period
(p
>
0.05).
was
analyzed
for
sodium,
potassium,
creatinine,
and
cortisol
by
standard
automated
procedures
and
metabolites
of
cortisol.
Metabolites
were
deter-
mined
by
gas
chromatography-mass
spectrometry
[13].
This
enabled
us
to
estimate
the
activity
of
11-1i-HSD2,
given
as
urinary
cortisol
and
cortisone
ratio
[14].
Cortisol
metabolites
were
calculated
as
the
sum
of
a-cortolone,
b-cortolone,
a-cortol,
b-cortol,
cortisone
(E),
cortisol
(F),
5b-tetrahydrocortisol
(THF),
5a-tetrahydrocortisol
(a-THF),
and
tetrahy-
drocortisone
(THE).
0.9
-
0.6
-
0.3
-
0.3
-
0.6
-
0.9
-
Placebo
Dexamethasone
Figure
6.
Change
in
diuresis
in
the
placebo
and
dexamethasone
period
(p
>
0.05,
n
=
9).
Blood
samples
The
blood
samples
were
collected
every
morning
at
8
a.m.
Each
sample
was
analyzed
for
hemoglobin,
glucose,
sodium,
potassium,
creatinine,
cortisol,
and
aldosterone.
S-aldosterone
was
measured
using
a
commercial
kit
(Coat-A-Count).
On
day
2
samples
were
further
analyzed
for
bilirubin,
INR,
albumin,
and
coagulation
factors
in
order
to
calculate
MELD
score
and
Child
Pugh
Score
[15-17].
Statistics
and
calculations
All
calculations
and
graphic
design
were
performed
using
Microsoft
Office
Excel
2007.
To
compare
the
dexamethasone
period
with
the
placebo
period,
Wilcoxon
signed
rank
test
was
used.
Mann
Whitney
test
was
performed
in
order
to
rule
out
the
possibility
of
carry-over
effects
and
period
effects.
Levels
of
significance
were
p
<
0.05.
Results
are
unless
otherwise
stated
presented
as
median
and
range.
Results
Twelve
patients
participated
in
the
study.
Three
were
later
excluded:
two
due
to
previously
unknown
diabetes
mellitus
and
one
did
not
wish
to
complete
the
study.
Of
the
remaining
nine
patients
the
Child
Pugh
score,
at
the
time
of
inclusion,
was
A
in
two
patients,
B
in
six
patients
and
C
in
one
patient.
Other
patient
characteristics
are
shown
in
Table
I.
No
carry-over
effect
or
period
effects
were
demonstrated.
Chang
e
in
diures
is
(
L
/day
)
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0,
C'
00
Crl
4:
5
Crl
N.
CT
N.1
t.!
E
E
a
E
°
E
E
In
in
41
Ta
ble
II.
Resu
lts
from
day
3
an
d
day
5
in
t
he
tw
o
p
er
io
ds.
1034
M.
H.
Hansen
et
al.
Urinary
sodium
excretion
increased
significantly
(p
<
0.05)
in
the
dexamethasone
period
compared
with
the
placebo
period.
The
increase
was
55.1
(-26.4-168.7)
mmol/day
(dexamethasone
-
placebo)
(Figure
3).
During
the
placebo
period
S-cortisol
was
within
normal
range
and
did
not
change
significantly,
the
median
being
495.0
(314.0-654.0)
nmol/L
in
the
basal
period
and
436.0
(193.0-676.0)
nmol/L
on
day
5.
In
the
dexamethasone
period
S-cortisol
chan-
ged
significantly
from
455.5
(252.5-843.0)
nmol/L
in
the
basal
period
to
40.0
(17.0-80.0)
nmol/L
on
day
5,
indicating
significant
suppression
of
cortisol
production.
The
relative
decrease
in
S-cortisol
was
92.3%
(82.7-93.4%)
(Figure
4).
In
accordance
with
this,
urinary
excretion
of
cortisol
meta-
bolites
declined
significantly
during
treatment
with
dexamethasone.
No
significant
difference
was
found
in
sodium
intake
(Figure
5).
As
per
the
patients'
diet
sheets
the
median
sodium
intake
in
the
placebo
period
was
118.0
(74.5-227.0)
mmol/day.
In
comparison,
the
median
sodium
intake
in
the
dexamethasone
period
was
109.3
(72.2-247.0)
mmol/day.
When
comparing
the
dexamethasone
period
with
the
placebo
period
the
levels
of
B-glucose
increased
statistically
significant
0.4
(-0.4-1.7)
mmol/L/day.
Median
B-glucose
level
on
day
5
in
the
dexametha-
sone
period
was
6.3
(5.5-9.6)
mmol/L.
S-aldosterone,
urine
Na/K-ratio,
urine-cortisol-
cortisone
ratio,
body
weight,
mean
arterial
pressure
and
diuresis
(Figure
6)
did
not
change
significantly
when
comparing
the
dexamethasone
period
with
the
placebo
period.
S-aldosterone
levels
at
baseline
were
359.5
(32-970.06)
pg/mL
(normal
range
in
the
-d
recumbent
position
being
10-160
pg/mL).
a
Discussion
o
In
this
study
the
aim
was
to
elucidate
the
role
of
2
glucocorticoids
in
sodium
retention
in
decompensated
cirrhotic
patients,
and
thereby
the
possible
actions
of
glucocorticoids
on
the
MR.
To
our
knowledge
this
hypothesis
has
not
previously
been
examined.
This
was
;.7
accomplished
by
suppressing
cortisol
in
plasma
by
(9)
administration
of
dexamethasone.
We
found
that
the
urinary
sodium
excretion
increased
O
significantly
when
S-cortisol
was
suppressed.
This
indicates
that
the
renal
sodium
handling
in
patients
with
decompensated
cirrhosis
is
dependent
upon
the
presence
of
endogenous
glucocorticoids.
O
The
change
in
sodium
handling
was
not
caused
by
different
levels
of
sodium
intake
in
the
two
.0
periods.
Estimated
from
the
patients'
diet
sheets,
the
difference
between
the
two
periods
was
small
Glucocorticoids
and
sodium
retention
1035
and
could
not
account
for
the
increase
in
sodium
excretion.
Other
parameters
which
might
affect
sodium
handling
were
S-aldosterone
and
the
activity
of
renal
11-1i-HSD2.
These
did
not
change
significantly
after
administration
of
dexamethasone
and
thus
unlikely
to
account
for
the
increase
in
urinary
sodium
excretion.
The
biological
activity
of
MR
is
indirectly
measured
as
urinary
Na/K-ratio.
This
was
increased
indicating
decreased
activation
of
the
MR
during
dexameth-
asone
treatment,
however,
not
within
the
limits
of
statistical
significance.
This
supports
the
hypothesis
that
cortisol
in
cirrhotic
patients
activates
the
MR
even
though
some
cirrhotic
patients
may
exhibit
adre-
nal
insufficiency
[18].
The
median
S-aldosterone
level
indicates
that
our
patients
as
a
group
have
hyper-
aldosteronism.
However,
two
patients
had
normal
levels
of
S-aldosterone.
In
both
patients
the
change
in
natriuresis
was
within
the
lower
quartile.
The
effect
of
dexamethasone
on
sodium
excretion
has
previously
been
studied
in
healthy
subjects
given
dexamethasone
for
five
days.
In
this
trial
dexameth-
asone
also
caused
increased
urinary
sodium
excre-
tion.
However,
the
dosage
used
was
8
mg/day
(four
times
higher
dosage
than
given
in
our
study).
Fur-
thermore,
the
increase
in
natriuresis
was
only
attained
after
4
days
of
treatment
[19].
This
suggests
a
differ-
ent
mechanism
than
the
one
seen
in
our
study.
In
addition,
dexamethasone
does
not
functionally
bind
to
the
MR
in
vivo
and
does
not
influence
the
activity
of
the
epithelial
sodium
channels
[20].
Consequently,
a
direct
effect
of
dexamethasone
on
natriuresis
is
unlikely.
Along
with
increased
urinary
sodium
excretion
one
would
expect
an
increase
in
the
diuresis.
In
this
study
we
found
no
statistically
significant
changes.
There
was,
however,
a
clear
tendency
of
increased
diuresis
when
dexamethasone
was
adminis-
tered
(Figure
6).
A
larger
study
might
demonstrate
a
significant
difference.
In
the
present
study
we
saw
a
small,
but
statistically
significant
increase
in
B-glucose
levels.
This
is
a
known
side
effect
of
dexamethasone
treatment.
One
might
fear
that
increased
B-glucose
levels
would
lead
to
osmotic
diuresis,
but
the
median
increase
being
0.4
mmol/L
it
is
unlikely
to
be
of
importance.
How-
ever,
one
patient
attained
a
B-glucose
level
of
9.6
mmolfL
on
day
5.
This
value,
when
combined
with
a
meal,
may
have
caused
mild
osmotic
diuresis.
This
does
not
seem
to
be
the
case,
since
this
patient's
increase
in
diuresis
equals
the
median
increase.
It
is,
therefore,
unlikely
that
the
increased
natriuresis
was
due
to
glucosuria.
The
increased
natriuresis
could
also
be
caused
by
an
increase
in
blood
pressure.
However,
there
was
no
significant
difference
in
mean
arterial
pressure
thus
demonstrating
no
contribution
to
the
increase
in
natriuresis.
The
importance
of
11-1i-HSD2
is
illustrated
by
the
clinical
consequences
of
loss
of
function
mutation
in
the
11-1i-HSD2
gene,
which
lead
to
the
syndrome
of
apparent
mineralocorticoid
excess,
a
rare
form
of
juvenile
hypertension
caused
by
activation
of
MR
by
glucocorticoids.
Established
treatment
of
this
dis-
order
includes
dexamethasone
[21],
which
support
the
importance
of
our
findings
in
this
study.
Thus
the
effect
of
dexamethasone
on
sodium
han-
dling
in
cirrhosis
could
be
of
clinical
significance.
It
is
well
known
that
treatment
with
MR
antagonists
increases
urinary
sodium
excretion
significantly
[22].
Most
patients
(eight
out
of
nine)
in
this
study
already
received
diuretics.
This
treatment
was
iden-
tical
for
each
patient
in
the
two
periods
and
changes
in
medication
cannot
be
the
cause
of
the
increased
sodium
excretion
seen
in
this
study.
The
effect
is,
therefore,
additional
to
the
treatment
with
diuretics.
As
seven
out
of
nine
patients
received
an
MR
antag-
onist,
the
observed
natriuresis
after
dexamethasone
probably
represented
a
blunted
effect.
In
summary
this
study
demonstrated
an
increased
renal
sodium
excretion
in
patients
with
decompen-
sated
cirrhosis
when
S-cortisol
level
was
suppressed
by
the
administration
of
dexamethasone.
The
effect
was
not
due
to
changes
in
S-aldosterone
or
renal
11-1i-HSD2
activity.
This
suggests
that
the
action
of
glucocorticoids
on
the
MR
plays
a
significant
role
in
the
renal
sodium
retention
in
patients
with
alcoholic
cirrhosis
of
the
liver.
The
impact
of
gluco-
corticoids
in
sodium
retention
should
be
investigated
further
in
a
larger
and
perhaps
more
heterogeneous
group
of
cirrhotic
patients
and
compared
with
the
impact
on
sodium
handling
in
normal
subjects.
Declaration
of
interest:
The
authors
report
no
conflicts
of
interest.
The
authors
alone
are
responsible
for
the
content
and
writing
of
the
paper.
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