Effects of acute protein loads of different sources on glomerular filtration rate


Dhaene, M.; Sabot, J.P.; Philippart, Y.; Doutrelepont, J.M.; Vanherweghem, J.L.

Kidney International. Supplement 22: S25-S28

1987


Three men and 3 women 24 to 31 years old eating a normal diet (protein 1.2 g/kg body weight) underwent pre- and postprandial creatinine clearance estimations after 2 acute protein loads: protein 2 g/kg body weight given in the form of beef or a dietetic preparation, Fortimel, repeated after 1 week. The main differences in protein loads were an absence of carbohydrate in meat, a greater amount of linoleic acid in Fortimel and different proportions of some amino acids. Per g protein meat contains more arginine (x 2), alanine (x 1.8) and glycine (x 2.5) but less proline (x 0.4) than Fortimel. Glomerular filtration rate was higher after red meat intake and postprandial urea excretion was similar after either treatment. After red meat intake there was a strong correlation between the postprandial increases in urea excretion and the increments in creatinine clearances.

Kidney
International.
Vol.
32.
Suppl.
22
(1987).
pp.
S-25-S-28
Effects
of
acute
protein
loads
of
different
sources
on
glomerular
filtration
rate
MICHEL
DHAENE,
JEAN-PIERRE
SABOT,
YVAN
PHILIPPART,
JEAN-MARC
DOUTRELEPONT,
and
JEAN-LOUIS
VANHERWEGHEM
Departments
of
Nephrology
and
Clinical
Chemistry,
University
Clinics
of
Brussels
and
Hopital
Erasme,
Brussels,
Belgium
Protein
intake
has
been
shown
to
raise
the
glomerular
filtra-
tion
rate,
and
recently
Bosch
et
al
[1,
2]
have
used
this
property
to
establish
the
maximal
renal
filtration
capacity
(that
is,
the
peak
of
glomerular
filtration
rate
following
an
acute
protein
load).
The
difference
between
peak
and
baseline
glomerular
filtration
rate
has
been
called
the
renal
reserve.
Since
vegetarians
have
been
shown
to
exhibit
a
lower
base-
line
glomerular
filtration
rate
[1],
it
may
be
asked
if
all
dietary
proteins
share
the
same
potency
to
raise
the
filtration
rate.
The
present
study
compares,
in
healthy
subjects,
the
effects
of
red
cooked
meat
and
of
a
dietetic
preparation
with
an
equivalent
amount
of
protein
but
with
another
distribution
of
amino
acids.
Subjects
and
methods
Six
healthy
subjects
(three
female,
three
male)
aged
24
to
31
years
and
ingesting
a
regular
diet
(1.2
g
protein/kg
body
weight)
underwent
pre-
and
postprandial
creatinine
clearance
measure-
ments
after
two
acute
protein
loads.
These
two
protein
rich
meals
each
averaged
2
g
protein/kg
body
weight,
and
were
given
at
a
one
week
interval
in
the
exclusive
form
of
red
cooked
meat
(beef)
or
of
a
dietetic
preparation
called
Fortimel
(Nutricia,
Bornem,
Belgium).
Respective
composition
of
both
meals
is
given
in
Table
1.
Subjects
were
fasting
and
began
the
protocol
by
drinking
20
ml/kg
of
water
in
30
minutes.
Subsequent
urine
volumes
were
replaced
in
equal
amounts
of
water.
Three
successive
45-minute
collections
of
urine
samples
were
obtained
before
the
protein
rich
meal.
Blood
samples
for
plasma
creatinine
measurements
were
taken
at
the
beginning
of
each
urine
collection
period
and
a
mean
plasma
value
was
calculated
for
each
period.
Baseline
glomerular
filtration
rate
was
calculated
as
the
mean
value
of
the
successive
creatinine
clearances.
Baseline
urea
excretion
was
the
mean
value
of
the
computed
urea
excretion
of
the
successive
collection
periods.
After
completion
of
the
baseline
collections,
a
total
protein
intake
of
2
g/kg
body
weight
was
ingested
in
45
minutes
in
the
form
of
either
red
meat
or
Fortimel.
The
whole
procedure
was
repeated
a
week
later
with
the
alternative
meal.
After
the
protein
load,
urea
excretion
and
creatinine
clearances
were
determined
on
four
successive
45-minute
collection
periods.
Received
for
publication
February
4,
1987
1987
by
the
International
Society
of
Nephrology
Postprandial
glomerular
filtration
rate
and
urea
excretion
were
calculated
as
the
mean
value
of
the
successive
measurements.
In
order
to
exclude
a
possible
influence
of
exogenous
creat-
inine
brought
by
the
cooked
meat
on
the
creatinine
clearances,
simultaneous
inulin
clearances
were
conducted
in
one
(Subject
#6)
of
the
six
healthy
subjects,
in
six
other
normal
volunteers,
and
in
three
patients
with
moderate
renal
insufficiency
before
and
after
the
red
meat
or
Fortimel
load.
Following
a
priming
bolus
of
50
mg/kg
body
weight,
inulin
was
infused
to
maintain
a
plasma
concentration
of
approximately
25
mg/c11.
Samples
were
drawn
and
clearances
calculated
as
described
above.
Creatinine
was
measured
by
means
of
the
Jaffe
rate
method,
and
urea
was
determined
by
means
of
the
enzymatic
conductivity
rate
method.
Inulin
levels
were
established
using
the
method
of
Heyrovsky
[3].
All
measures
of
clearances
are
expressed
per
1.73
m
2
of
body
surface
area.
Statistical
comparisons
were
made
using
a
paired
"Student's"
t-test,
and
results
were
expressed
as
mean
±
SEM.
Results
Figure
1
depicts
the
glomerular
filtration
response
to
both
protein
loads.
From
similar
baseline
levels,
glomerular
filtration
rate
reached
higher
levels
after
red
meat
intake.
This
is
clearly
illustrated
in
Figure
2;
from
a
mean
level
of
114.3
±
3.9
ml/min/1.73
m
2
,
the
filtration
rate
rose
significantly
to
146.7
±
6.7
ml/min/1.73
m
2
after
red
meat
intake.
With
Fortimel
inges-
tion,
the
mean
glomerular
filtration
rate
increased
from
119.5
±
5.3
to
a
postprandial
level
of
129.8
±
3.8
ml/min/1.73
m
2
.
Peak
filtration
was
thus
lower
than
after
red
meat
intake,
although
the
difference
did
not
reach
statistical
significance
(P
=
0.105).
However,
when
comparing
the
renal
reserve
elicited
by
both
meals
(32.4
±
4.8
versus
10.3
±
2.2
ml/min/1.73
m
2
),
the
difference
became
significant
(P
<
0.05).
Changes
in
urinary
urea
excretion
are
presented
in
Figure
3.
Baseline
levels
were
identical
in
both
experiments:
17.1
±
1.7
mg/min
and
17.3
±
1.4
mg/min.
Postprandial
urea
excretion
increased
in
the
same
manner
after
red
meat
or
Fortimel,
and
averaged
26.2
±
2.3
mg/min
and
26.4
±
1.3
mg/min,
respec-
tively.
No
correlation
was
found
between
urea
output
and
baseline
or
postprandial
glomerular
filtration
rate.
After
red
meat
intake,
a
strong
correlation
(r
=
0.97,
P
<
0.001)
was
demonstrated
between
the
postprandial
increases
of
urea
excretion
and
the
increments
in
creatinine
clearances
(Fig.
S-25
S-26
Dhaene
et
al
Table
1.
Composition
of
red
cooked
meat'
and
fortimel
Red
meat
Fortimel
Fortimel
Red
cooked
meat
Carbohydrates
glg
protein
Lipids
gig
protein
Linoleic
acid
Sodium
mglg
protein
0.93
0.22
0.11
5.0
0
0.65
0.015
5.0
Amino
acids
mgig
protein
L-isoleucinee
L-leucine`
L-lysine`
L-methionine
46
92
75
24
48
81
89
27
L-cystine
8
13
L-phenylalaninec
52
44
L-tyrosine
46
36
L-threonine
42
46
L-tryptophan`
14
11
L-valinec
56
50
L-arginine
32
63
L-histidinec
26
34
L-alanine
33
58
L-asparticacid
74
90
L-glutamic
acid
216
153
glycine
L-proline
19
88
49
38
L-serine
56
40
a
From
WEBER
C,
POST
GB,
and
SWAGER
TW
in:
Informatorium
voor
voeding
en
dietetiek,
edited
by
Samson,
Holland,
p.
Vila
11:
1976.
b
From
Nutricia
Bornem
Belgium
Essential
amino
acids
160
150
140
130
120
110
-
100
Protein
load
Time
Fig.
1.
Effects
of
acute
protein
loads
r•
red
cooked
meat,
0
Fortimel)
on
glomerular
filtration
rate.
(mean
:t
sEm).
4).
No
relationship
was
appreciable
between
these
parameters
after
Fortimel
ingestion.
The
relationship
of
creatinine
clearance
to
inulin
clearance
is
shown
in
Figure
5.
The
inulin
clearance
values
agreed
well
with
the
respective
creatinine
clearances
(r
=
0.94)
for
the
three
experimental
designs
(basal
values,
postprandial
values
with
red
cooked
meat,
and
postprandial
levels
with
Fortimel).
Even
when
considering
only
measurements
with
red
cooked
meat,
no
differences
between
pre—
and
postprandial
values
were
found
(r
=
0.95
versus
r
=
0.96)
and
the
ratio
of
inulin
clearance
to
creatinine
clearance
remained
unchanged
for
each
subject.
Pre-
Post
Post-
Protein
load
60
-
40
-
°
:H
20
-
Red
meat
Fortimel
Fig.
2.
E
f
fects
of
both
acute
protein
loads
on
glomerular
filtration
rate
pre-
and
postprandial
mean
values
in
six
normal
subjects.
Renal
reserve
elicited
by
red
meat
and
Fortimel
intake.
Discussion
This
study
was
designed
to
compare
the
effects
of
different
acute
protein
loads
on
glomerular
filtration
rate.
Increases
in
glomerular
filtration
rate
elicited
by
red
cooked
meat
appeared
to
be
significantly
more
important
than
those
following
protein
intake
of
a
different
origin.
Table
I
gives
the
respective
com-
positions
of
red
meat
and
Fortimel.
On
the
basis
of
an
equal
quantity
of
protein
given
with
both
meals,
the
main
differences
consist
of
an
absence
of
carbohydrate
in
red
meat,
a
greater
proportion
of
linoleic
acid
in
Fortimel,
and
different
proportions
of
some
amino
acids.
Per
gram
of
protein,
red
meat
contains
more
arginine
(2
x
),
alanine
(1.8
x),
and
glycine
(2.5
x)
but
less
proline
(0.4
x)
than
Fortimel.
Nutritive
value
in
regard
to
essential
amino
acids
is
comparable.
Aside
from
the
possible
role
of
the
nature
of
the
proteins,
other
factors
could
explain
the
present
observations.
First,
a
delayed
or
less
complete
digestive
absorption
of
Fortimel
could
account
for
a
smaller
effect
of
glomerular
filtration
rate.
How-
ever,
since
postprandial
urea
output
was
the
same
following
red
meat
or
Fortimel
ingestion,
this
hypothesis
can
be
ruled
out.
Another
potential
factor
could
have
been
an
artifactual
increase
in
postprandial
creatinine
clearances
introduced
by
the
exoge-
nous
creatinine
from
cooked
red
meat
[4,
5,
6].
In
agreement
with
the
results
of
Bosch
et
al
[2],
our
comparison
of
simulta-
G
F
R,
m
l
/m
in
/1.
7
3m
2
G
F
R,
m
l/m
in
/
1.
73m
2
160
-
150
-
140
130
-
120
-
110
100
-
Protein
intake
and
glomerular
filtration
rate
S
-
27
Crea
t
in
ine
c
learance,
m
l/m
in
Ure
a
e
xc
re
t
io
n,
mg
/m
in
27
-
23
-
19
-
15
-
Pre-
Post-
Pre-
Post-
Protein
load
Fig.
3.
Effects
of
red
meat
(right)
and
Fortimel
(left)
intake
on
urea
excretion
in
six
normal
subjects.
Pre-
and
postprandial
mean
values
±
SEM.
100
-
y
0.58
3.7
80
-
r
-
0.97
P<0.001
60
-
40
-
20
-
0
20
40
60
80
100
Increase
of
urea
excretion,
%
Fig.
4.
Relationship
between
postprandial
increases
in
urea
excretion
and
creatinine
clearances,
expressed
in
percent
relative
to
their
base-
line
levels.
Symbols
are:
(•)
postprandial
increases
following
red
meat
ingestion,
(x)
postprandial
increases
following
Fortimel
ingestion.
neous
measurements
of
inulin
and
creatinine
clearances
elimi-
nate
this
possibility.
As
already
suggested
by
Bosch
et
al,
this
shows
endogenous creatinine
clearance
to
be
a
reliable
indica-
tor
of
the
changes
in
glomerular
filtration
rate
occuring
after
a
protein
rich
meal,
even
a
meal
in
the
form
of
red
cooked
meat.
According
to
Brenner
et
al
[7],
protein
induced
hyperfiltration
would
be
the
result
of
a
decreased
vascular
resistance
affecting
mainly
the
afferent
arterioles.
The
mechanisms
underlying
these
hemodynamic
alterations
are
still
unknown.
Amino
acids
are
known
to
increase
renal
blood
flow
and
glomerular
filtration
rate
in
animals
and
humans
[8-12].
However,
during
perfusion
of
isolated
rate
kidney
by
a
solution
of
amino
acids,
effects
on
glomerular
filtration
rate were
smaller
[13]
or
even
absent
[14]
despite
evident
intrarenal
vasodilatation.
This
lack
of
effect
had
been
attributed
to
a
filtration
disequilibrium
due
to
the
experi-
mental
conditions
[14].
An
important
feature
is
that,
at
physio-
logical
concentrations,
some
amino
acids,
particularly
those
known
to
be
extracted
by
the
kidney
in
vivo
[15],
appeared
to
produce
an
increase
in
renal
blood
flow
while
other
amino
acids
had
no
effect
[14].
This
vasodilatory
action
seems
to
be
linked
180
-
160
-
y
0.9
24.4
r
0.94
x
140
-
O
120
-
100
-
X•
x•
80
-
60
-
40
-
20
-
0
20
40
60
80
100
Inulin
clearance,
mlimin
Fig.
5.
Relationship
between
inulin
and
creatinine
clearances.
Sym-
bols
are:
(•
baseline
clearances.
(x)
postprandial
clearances
(red
cooked
meat),
(0)
postprandial
clearances
(Fortimel).
to
the
use
of
these
amino
acids
as
metabolic
substrates
by
the
kidney
[14].
In
vivo,
renal
uptake
of
amino
acids
involves
glutamine,
proline,
glycine,
and
alanine.
The
amino
acid
com-
position
of
red
meat
and
Fortimel
are
similar,
except
for
alanine,
glycine,
proline,
and
arginine.
It
is
thus
possible
that
the
relative
distribution
of
these
amino
acids,
and
especially
the
higher
content
of
glycine
and
alanine
in
red
meat.
may
play
a
role
in
the
variable
postprandial
increases
in
glomerular
filtra-
tion
rates
following
red
meat
or
Fortimel
intake.
Instead
of
a
direct
effect
on
renal
hemodynamics,
amino
acids
could
also
be
active
through
the
release
of
the
hypothetical
liver
hormone
(the
so-called
glomerulopressin)
[16].
On
the
other
hand,
a
close
correlation
has
been
noted
between
increases
in
urea
excretion
and
increases
in
creatinine
clearances
following
red
meat
in-
take.
The
absence
of
a
similar
correlation
after
ingestion
of
Fortimel
confirms
that
the
hemodynamic
effects
observed
are
not
simply
the
result
of
a
greater
amount
of
protein,
but
that
other
qualitative
factors
are
operative.
Carbohydrates
are
present
in
Fortimel
and
not
in
red
meat.
Their
role,
if
any,
could
thus
be
inhibitory,
but
up
to
the
present
little
data
support
such
an
action.
On
the
contrary,
glucose
infusion
has
been
shown
to
raise
glomerular
filtration
rate
[17,
18]
Red
meat
fat
content
is
about
thrice
that
of
Fortimel.
It
has
been
suggested
that
progression
of
chronic
renal
failure
may
also
be
mediated
by
lipids
[19].
Evidence
in
favor
of
this
hypothesis
remains
very
weak.
On
the
other
hand,
linoleic
acid
has
been
shown
to
preserve
renal
function
in
rat
remnant
Inc
reas
e
o
f
c
rea
t
in
ine
c
lea
ra
nce,
%
120
140
S-28
Dhaene
et
al
kidney
[20]
and
in
marine
apoferritin-induced
immune
complex
nephritis
[21].
A
possible
interference
with
glomerular
filtration
cannot
thus
be
totally
discarded.
According
to
Brenner
et
al
[7],
reduction
of
all
protein
intake
should
be
recommended
for
the
treatment
of
chronic
renal
insufficiency.
Our
findings
would
imply
that
all
proteins
do
not
share
the
same
capacity
to
induce
glomerular
hyperfiltration.
Thus,
the
nature
of
the
proteins
has
to
be
taken
into
account
in
the
dietetic
prescription.
Further
studies
are
required
to
grade
different
proteins
according
to
their
propensity
to
provoke
glomerular
hyperfiltration.
Acknowledgments
The
skillful!
assistance
of
Brigitte
Prekwoski
and
Marie
Barea,
dietitians,
and
the
secretarial
assistance
of
Chantal
Tholet
are
gratefully
acknowledged.
Reprint
requests
to
Michel
Dhaene,
Cliniques
Universitaires
de
Bruxelles,
Hopital
Erasme—Service
Nephrologie,
Route
de
Lennik
808,
1070
Brussels,
Belgium.
References
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1984
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Exp
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1982
10.
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GW,
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178:165-167,
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11.
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LIE
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J
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N
Engl
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13.
MAACK
T,
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V,
TATE
SS,
MEISTER
A:
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(AA)
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(abstract)
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M,
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FH:
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in
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Am
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JJ,
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DE:
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FC
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PA
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A,
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Glomerular
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after
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during
glucagon
infusion
and
in
insulin-depend-
ent
diabetes
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by
a
liver
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1984
17.
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Acta
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in
normal
man
and
in
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21:368-373,
1981
19.
MOORHEAD,
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EL-NAHAS
M,
CHAN
MK.
VARGHESE
Z:
Lipid
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in
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progressive
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and
tubulo-inter-
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Lancet
2:1309-1311,
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20.
BARCELLI
V,
WEISS
H,
POLLAK
VE:
Effects
of
a
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glandin
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on
the
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of
experimentally
induced
chronic
renal
failure.
J
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100:786:787,
1982
21.
KHER
V,
BARCELLI
V,
WEISS
M,
POLLAK
VE:
Effect
of
dietary
linoleic
acid
enrichment
on
induction
of
immune
complex
nephritis
in
mice.
Nephron
39:261-266,
1985