Glomerular filtration rate in response to an acute protein load


von Herrath, D.; Saupe, J.; Hirschberg, R.; Rottka, H.; Schaefer, K.

Blood Purification 6(4): 264-268

1988


The effect of a protein load on the glomerular filtration rate (measured as creatinine clearance) was studied in normal subjects, healthy vegetarians, patients with advanced liver disease, patients with moderate renal failure and in normal volunteers being pretreated with aspirin or sulindac. Only patients with liver disease were not capable of increasing their glomerular filtration rate after the protein challenge, a finding which suggests that the liver might be of importance for the adequate renal reserve. It is of note that neither the application of nonsteroidal anti-inflammatory drugs nor the existence of a moderate renal failure modify the response to a protein load.

01988
S.
Karger
AG,
Basel
Blood
Purification
6:
264-268
(1988)
0253-5068/8810064-026452.7510
Glomerular
Filtration
Rate
in
Response
to
an
Acute
Protein
Load'
D.
von
Herrath
a
,
J.
Saupea,
R.
Hirschberga,
H.
Rottkab,
K.
Schaefer"
Medizinische
Abteilung
IL
St.
Joseph-Krankenhaus
1.
and
b
Institut
ftir
Sozialmedizin
and
Epidemiologic.
Bundcsgesundhcitsamt,
Berlin
Key
Words.
Protein
load
Vegetarians
Liver
cirrhosis
Nonsteroidal
anti-inflammatory
drugs
Functional
renal
reserve
Abstract.
The
effect
of
a
protein
load
on
the
glomerular
filtration
rate
(measured
as
cre-
atinine
clearance)
was
studied
in
normal
subjects,
healthy
vegetarians,
patients
with
advanced
liver
disease,
patients
with
moderate
renal
failure
and
in
normal
volunteers
being
pretreated
with
aspirin
or
sulindac.
Only
patients
with
liver
disease
were
not
capable
of
increasing
their
glomerular
filtration
rate
after
the
protein
challenge,
a
finding
which
suggests
that
the
liver
might
be
of
importance
for
the
adequate
renal
reserve.
It
is
of
note
that
neither
the
application
of
nonsteroidal
anti-inflammatory
drugs
nor
the
existence
of
a
moderate
renal
failure
modify
the
response
to
a
protein
load.
The
profound
influence
of
dietary
com-
position
and
feeding
pattern
on
renal
func-
tion
has
been
repeatedly
stressed
in
recent
literature
[1-3].
Data
on
the
influence
of
an
acute
protein
challenge
on
the
glomerular
fil-
tration
rate
(GFR)
in
humans,
however,
are
surprisingly
scarce.
In
1983,
Bosch
et
al.
[4]
reported
for
the
first
time
that
an
acute
pro-
This
paper
was
presented
at
the
International
Symposium
'Diet
and
the
Progression
of
Renal
Dis-
ease',
Berlin
1986.
2
We
thank
Mrs.
D.
Weisselberg
for
typing
the
manuscript.
tein
load
induced
an
increase
in
the
GFR.
More
recently,
similar
findings
have
been
communicated
by
Vanrenterghem
et
al.
[5]
and
Mansy
et
al.
[6].
Hostetter
[7]
observed
not
only
in
increase
of
the
GFR
but
also
an
increased
natriuresis
and
an
augmented
ex-
cretion
of
cyclic
GMP
in
10
volunteers
after
a
meat
meal.
We
were
interested
in
testing
the
effect
of
a
protein
load
not
only
in
nor-
mal
subjects
but
also
in
healthy
vegetarians
[8].
We
assumed
that
changes
occurring
in
the
GFR
would
be
more
easily
demonstrated
in
a
population
which
had
been
shown
to
have
a
lower
GFR
than
nonvegetarian
sub-
Glomerular
Filtration
Rate
after
Protein
Loading
265
jects.
Furthermore,
it
seemed
of
interest
to
study
whether
or
not
nonsteroidal
anti-in-
flammatory
drugs
(NSAID)
would
prevent
the
increase
in
the
GFR
in
healthy
subjects,
as
it
has
recently
been
claimed
that
prosta-
glandins
might
be
involved
in
the
renal
re-
sponse
to
a
protein
load
[9].
Finally,
data
will
be
reported
on
the
GFR
response
after
a
protein
load
in
patients
suffering
from
se-
vere
liver
disease
[10].
Patients
and
Methods
The
investigations
were
conducted
in
two
differ-
ent
modes:
clearance
studies
(creatinine
clearance,
CrCI)
were
carried
out
either
by
collecting
urine
over
24
h
(study
A,
vegetarians:
study
B,
patients
with
liver
disease),
or
alternatively
by
collecting
urine
at
30-min
intervals
(study
C,
normal
subjects
with
and
without
NSAID;
study
D,
patients
with
mild
renal
failure).
The
serum
and
urinary
creatinine
values
were
mea-
sured
using
standardized
methods.
The
values
were
corrected
for
body
weight
and
body
surface.
The
sta-
tistical
evaluation
of
the
data
was
carried
out
using
the
t
test
for
comparison
of
paired
observations.
In
all
studies
a
milk
protein
load
of
about
1.5
g/kg
body
weight
was
received
by
all
investigated
subjects
after
a
control
clearance.
In
studies
C
and
D,
a
continuous
urine
flow
was
maintained
by
administering
20
ml/kg
body
weight
fluid
to
all
subjects
60
min
before
the
clearance
studies
were
initiated.
To
test
the
effect
of
NSAID,
a
therapy
with
either
1,500
mg
of
acetylsali-
cyclic
acid
(ASA)
or
300
mg
of
sulindac
(SU)
was
started
24
h
before
the
protein
challenge.
The
drugs
were
also
administered
on
the
morning
the
CrC1
stud-
ies
took
place.
Informed
consent
was
obtained
from
all
investigated
subjects.
Results
The
mean
CrC1
of
the
investigated
vege-
tarians
was
65.5
±
22.3
ml/min
and
in-
creased
to
77.8
±
15.7
ml/min
after
the
pro-
tein
load.
It
is
of
note,
however,
that
only
5
NR
E
7
5
E
;-*
15
25
C
ro
8'
0
B
A
Fig.
I.
Effect
of
a
protein
load
in
healthy
vegetar-
ians.
R
=
Responders;
NR
nonrcsponders;
B
before
protein
load;
A
=
after
protein
load.
of
9
investigated
subjects
showed
a
signifi-
cant
increase
in
the
GFR,
whereas
the
re-
maining
4
subjects
even
revealed
a
slight
reduction
(fig.
1).
The
serum
creatinine
con-
centrations
remained
entirely
normal
in
all
vegetarians
and
likewise
showed
no
differ-
ences
between
the
responders
and
nonre-
sponders.
The
effects
of
the
protein
load
on
the
GFR
after
protein
challenge
in
patients
with
severe
liver
disease
are
presented
in
figure
2.
It
can
be
seen
that
the
majority
(5
of
8)
of
patients
could
not
increase
their
GFR
fol-
lowing
the
protein
challenge.
The
results
of
study
C
are
depicted
in
fig-
ure
3.
It
can
be
seen
that
all
healthy
subjects
but
I
showed
an
increase
in
the
GFR
ranging
between
3.0
and
21.0%
(mean
10.8
±
6.7%),
whereas
only
I
subject
showed
a
slight
de-
crease
of
4.5%
(fig.
3b).
With
regard
to
the
administered
NSAID,
it
is
noteworthy
that
neither
ASA
nor
SU
induced
significant
125
-
100
-
\
\
••••
\
\
A
75
-
\\
\
V
b
p
50
-
25
-
0
30
20
-
10
-
Crea
t
in
ine
c
lea
ra
nc
e,
¶.
c
ha
ng
e
0
-10-
30-
b
20-
to
-
0
1
-20-
266
von
Herrath/Saupe/H
irschberg/Rottka/Schaefer
Fig.
2.
Effect
of
a
protein
load
in
patients
with
severe
liver
disease.
B
Before
protein
load;
A
=
after
protein
load.
Fig.
3.
Effect
of
a
protein
load
in
healthy
subjects
before
(open
bars)
and
after
pretreatment
(hatched
bars)
with
acetylsalicylic
acid
(a)
or
SU
(b).
3
changes
in
the
GFR
response
after
a
protein
load,
as
4
subjects
were
still
able
to
augment
their
GFR
after
the
administration
of
the
NSAID.
In
addition,
the
results
do
not
allow
any
judgement
as
to
the
effect
of
ASA
com-
pared
to
SU.
Figure
4
shows
the
effect
of
a
protein
load
in
patients
suffering
from
renal
insufficien-
cy.
All
investigated
patients
showed
a
rise
in
GFR
of
between
9
and
76.5%
(mean
30.0
±
23.8%).
Discussion
The
results
obtained
from
our
studies
in-
dicate
that
almost
all
healthy
subjects
and
all
investigated
patients
with
mild
to
moderate
renal
failure
showed
an
increase
in
GFR
after
an
acute
oral
protein
load.
Further-
more,
the
administration
of
NSAID
was
not
consistently
capable
of
preventing
the
in-
crease
in
GFR.
The
investigated
vegetarians
revealed
a
significantly
reduced
GFR
under
normal
conditions;
after
a
protein
load
only
55
%
of
them
showed
an
adequate
rise
in
the
GFR
and
the
others
did
not
react
at
all.
Finally,
it
is
of
note
that
the
majority
of
patients
with
advanced
liver
disease
are
not
capable
of
increasing
their
GFR
after
a
pro-
tein
challenge.
Only
a
limited
number
of
studies
report
on
the
effect
of
a
protein
load
on
the
GFR
in
humans
under
the
conditions
we
have
cho-
sen
[4-7,
I
I].
Bosch
et
al.
[4]
observed
an
increase
in
the
GFR
of
more
than
40
ml/min
eo
70
-
Cr
Cr
2
10
Cr
2.90
Cr
395
375
2
30
a;
rp
20
-
a.
'
‘A'10
-
C
Glomerular
Filtration
Rate
after
Protein
Loading
267
Fig.
4.
Effect
of
a
protein
load
in
patients
with
moderate
renal
failure.
Cr
Serum
creatinine.
approximately
2
h
after
a
protein
load.
Oth-
ers
have
reported
a
rise
in
the
GFR
only
after
a
meat
load
[11
],
findings
which
have
not
been
confirmed,
however.
A
comparable
rise
in
the
GFR
was
observed
by
two
groups
[5,
6]
after
meat
protein
and
nonmeat
(milk)
protein.
Hostetter
[7]
investigated
the
effect
of
a
meat
meal
and
found
an
average
GFR
increase
of
28%
after
3
h.
Furthermore,
he
did
not
observe
any
change
in
prostaglandin
E
excretion,
a
finding
which
does
not
sup-
port
the
view
that
the
increase
in
the
GFR
might
be
due
to
alterations
in
the
prostaglan-
din
system.
Our
results
likewise
do
not
seem
to
support
the
hypothesis
that
prostaglan-
dins
might
be
of
major
importance
in
adap-
tation
of
the
GFR
after
a
protein
load.
It
is
of
note,
however,
that
others
have
recently
re-
ported
that,
in
subtotally
nephrectomized
rats,
an
acute
infusion
of
indomethacin
re-
duced
the
single
nephron
filtration
rate
by
decreasing
the
glomerular
plasma
flow
rate
and
the
ultrafiltration
coefficient
[9].
Alve-
strand
and
Bergstrom
[12]
have
suggested
that
patients
with
severe
liver
disease
might
suffer
from
a
deficiency
of
a
hormone,
glo-
merulopressin,
which
is
synthesized
by
the
liver
and
raises
the
GFR.
They
suggested
that
apart
from
hepatocellular
dysfunction,
the
chronic
protein
depletion
observed
in
many
patients
with
severe
liver
disease
might
be
of
some
importance
in
explaining
the
reduced
production
of
glomerulopressin
[12].
Our
data
demonstrate
that
such
pa-
tients
cannot
increase
their
GFR
after
a
pro-
tein
challenge,
which
could
imply
that
a
nor-
mal
liver
function
is,
in
fact,
necessary
for
the
kidney
to
augment
the
GFR
when
chal-
lenged
with
a
protein
load.
It
is
of
interest
that
Dratwa
et
al.
[13]
also
recently
reported
that
severe
liver
disease
prevents
the
rise
in
the
GFR
after
protein
loading.
A
lack
of
any
increase
in
the
GFR
was
also
observed
in
4
of
our
investigated
vegetarians.
However,
as
5
of
them
did
increase
their
GFR,
it
remains
speculative
whether
or
not
the
failure
to
increase
the
GFR
reflects
a
reduced
func-
tional
reserve
of
the
kidney
as
suggested
by
Bosch
et
al.
[4].
In
conclusion,
our
studies
have
demon-
strated
that
not
only
normal
subjects
but
even
patients
with
moderate
renal
failure
are
capable
of
augmenting
in
their
GFR
when
an
acute
protein
load
is
administered,
a
finding
which
was
also
observed
by
Bosch
et
al.
[4].
Furthermore,
our
data
have
not
revealed
any
evidence
that
the
rise
in
the
GFR
after
an
acute
protein
load
is
mediated
by
prostaglan-
dins
in
normal
subjects.
However,
addi-
tional
findings
suggest
that
the
liver
might
be
of
importance
for
the
adequate
renal
reserve
as
patients
suffering
from
severe
liver
failure
are,
in
spite
of
normal
scrum
creatinine,
incapable
of
increasing
their
GFR
after
a
protein
load.
268
von
Herrath/Saupe/Hirschberg/Rottka/Schaefer
References
I
Brenner.
B.M.;
Mcmcr,
T.W.;
Hostetter.
T.H.:
Dietary
protein
intake
and
the
progressive
nature
of
kidney
disease.
New
Engl.
J.
Mcd.
307:
652-
659
(1982).
2
Brenner,
B.M.:
Ncphron
adaptation
to
renal
in-
jury
or
ablation.
Am.
J.
Physiol.
249:
F324-F324
(1985).
3
Mitch,
W.E.;
Brenner,
B.M.;
Stein,
J.H.:
The
pro-
gressive
nature
of
renal
disease
(Churchill
Living-
stone,
New
York
1986).
4
Bosch,
J.P.;
Saccaggi.
A.;
Lauer.
A.;
Ronco,
C.;
Belledonne,
M.;
Glabman,
S.:
Renal
functional
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in
humans.
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of
protein
intake
on
glo-
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filtration
rate.
Am.
J.
Med.
75:
943-950
(1983).
5
Vanrentcrghem,
Y.;
Verberckmocs.
R.;
Roels.
L.;
Michielsen,
P.:
Glomerular
filtration
response
to
acute
protein
load.
Lancet
ii:
1360
(1985).
6
Mansy,
H.;
Tapson,
J.S.;
Fernandez,
J.;
Tapster,
S.;
Wilkinson,
R.:
Glomerular
filtration
response
to
acute
protein
load.
Lancet
ii:
1360
(1985).
7
Hostetter,
T.H.:
Human
renal
response
to
a
meat
meal.
Am.
J.
Physiol.
250:
F613-F618
(1986).
8
Hirschberg,
R.;
Rottka,
H.;
Herrath,
D.
von;
Pauls,
A.:
Schaefer,
K.:
Effect
of
an
acute
protein
load
on
the
creatinine
clearance
in
healthy
vege-
tarians.
Klin.
Wschr.
63.•
217-220
(1985).
9
Nath.
K.A.;
Chmielewski,
D.;
Hostetter,
T.H.:
Regulatory
role
of
prostaglandins
in
the
remnant
glomerulus.
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int.
29:
341
(1986).
10
Hirschberg,
R.;
Herrath,
D.
von;
PauIs,
A.;
Schaefer.
K.:
No
rise
in
glomerular
filtration
rate
after
protein
load
in
severe
liver
disease.
Lancet
ii:
1047-1048
(1984).
11
Jones,
G.;
Lee,
K.;
Swaminathan,
R.:
Glomerular
filtration
response
to
acute
protein
load.
Lancet
838
(1985).
12
Alvestrand,
A.;
Bergstrom,
J.:
Glomerular
hyper-
filtration
after
protein
ingestion,
during
glucagon
infusion,
and
in
insulin-dependent
diabetes
is
in-
duced
by
a
liver
hormone:
deficient
production
of
this
hormone
in
hepatic
failure
causes
hepatorenal
syndrome.
Lancet
i:
195-197
(1984).
13
Dratwa,
M.;
Van
Gossum,
M.;
Burette,
A.;
Wens,
R.;
Charlier,
L.;
Tielemans,
C.;
Conan,
F.;
Del-
tenrc,
V1.:
No
increase
in
glomerular
filtration
rate
after
protein
loading
in
cirrhotics
(Abstract).
1Vth
International
Congress
on
Nutrition
and
Metabo-
lism
in
Renal
Disease,
Williamsburg
1985.
D.
von
Herrath,
MD
Medizinische
Abteilung
II
St.
Joseph-Krankenhaus
I
Baumerplan
24
D-1000
Berlin
42