Effects of an acute protein load in comparison to an acute load of essential amino acids on glomerular filtration rate, renal plasma flow, urinary albumin excretion and nitrogen excretion


Braendle, E.; Kindler, J.; Sieberth, H.G.

Nephrology, Dialysis, Transplantation 5(8): 572-578

2013


Pre- and postprandial changes of inulin and PAH clearance, urinary albumin excretion and nitrogen excretion after an acute load of 1.4 g/kg body-weight of essential aminoacids (EAA) were compared to the changes after a load of the same amount of proteins in ten healthy subjects. Six of the volunteers underwent the same procedure in a third set of experiments, receiving only a water load instead of a test meal (control group). Inulin clearance showed a maximal increase of 27.6 +/- 2.3% after the EAA load, compared to 31.7 +/- 3.8% after the protein load. Parallel to the increase in inulin clearance, PAH clearance increased to 34.1 +/- 3.8% (EAA) compared to 35.5 +/- 3.4% (proteins). Urinary nitrogen excretion increased from a preprandial value of 8.7 +/- 1.6 mg/min to a postprandial value of 13.7 +/- 3.5 mg/min after the EAA load, while it increased after the protein load from 8.1 +/- 3.1 mg/min to 15.4 +/- 3.3 mg/min. Urinary albumin excretion increased from a preprandial value of 4.8 +/- 1.7 microg/min to a maximum of 13.5 +/- 4.7 microg/min after the EAA load. After the protein load the albumin excretion increased to maximum of 14.4 +/- 5.4 microg/min. Increased albumin excretion was associated with an increase in diuresis. Comparing both test meals, the only significant difference was observed in the postprandial values of urinary nitrogen excretion. In the control group inulin and PAH clearance and urinary nitrogen excretion did not change significantly after the water load, while parallel to an increase in postprandial diuresis urinary albumin excretion increased to a maximum of 11.6 +/- 5.1 microg/min. In comparison to the control group urinary albumin excretion was significantly greater 120-180 min after both test meals, although no significant difference was observed in urinary flow.

Nephrol
Dial
Transplant
(1990)
5:
572-578
©
1990
European
Dialysis
and
Transplant
Association—European
Renal
Association
Nephrology
Dialysis
Transplantation
Original
Article
Effects
of
an
Acute
Protein
Load
in
Comparison
to
an
Acute
Load
of
Essential
Amino
Acids
on
Glomerular
Filtration
Rate,
Renal
Plasma
Flow,
Urinary
Albumin
Excretion
and
Nitrogen
Excretion
E.
Braendle,
J.
Kindler
and
H.
G.
Sieberth
Department
of
Internal
Medicine
II,
RWTH
Aachen,
West
Germany
Abstract.
Pre-
and
postprandial
changes
of
inulin
and
PAH
clearance,
urinary
albumin
excretion
and
nitrogen
excretion
after
an
acute
load
of
1.4
g/kg
body-weight
of
essential
aminoacids
(EAA)
were
compared
to
the
changes
after
a
load
of
the
same
amount
of
proteins
in
ten
healthy
subjects.
Six
of
the
volunteers
underwent
the
same
procedure
in
a
third
set
of
experiments,
receiving
only
a
water
load
instead
of
a
test
meal
(control
group).
Inulin
clearance
showed
a
maximal
increase
of
27.6
±
2.3%
after
the
EAA
load,
compared
to
31.7
±
3.8%
after
the
protein
load.
Parallel
to
the
increase
in
inulin
clearance,
PAH
clearance
increased
to
34.1
±3.8%
(EAA)
compared
to
35.5
+
3.4%
(proteins).
Urinary
nitrogen
excretion
increased
from
a
preprandial
value
of
8.7
±
1.6
mg/min
to
a
postprandial
value
of
13.7
+
3.5
mg/min
after
the
EAA
load,
while
it
increased
after
the
protein
load
from
8.1
±
3.1
mg/min
to
15.4
±
3.3
mg/min.
Urinary
albumin
excretion
increased
from
a
preprandial
value
of
4.8±
1.7
µg/min
to
a
maximum
of
13.5
+
4.7
µg/min
after
the
EAA
load.
After
the
protein
load
the
albumin
excretion
increased
to
maximum
of
14.4
+
5.414/min.
Increased
albumin
excretion
was
associated
with
an
increase
in
diuresis.
Comparing
both
test
meals,
the
only
significant
difference
was
observed
in
the
postprandial
values
of
urinary
nitrogen
excretion.
In
the
control
group
inulin
and
PAH
clearance
and
urinary
nitrogen
excretion
did
not
change
significantly
after
the
water
load,
while
parallel
to
an
increase
in
postprandial
diuresis
urinary
Correspondence
and
offprint
requests
to:
E.
Braendle,
Department
of
internal
Medicine
ii.
RWTH
Aachen.
5100
Aachen,
West-Germany.
albumin
excretion
increased
to
a
maximum
of
11.6±
5.1
µg/min.
In
comparison
to
the
control
group
urinary
albumin
excretion
was
significantly
greater
120-180
min
after
both
test
meals,
although
no
significant
difference
was
observed
in
urinary
flow.
Key
words:
Essential
aminoacids;
Protein-induced
hyper-
filtration;
Protein
load;
Urinary
albumin
excretion;
Urinary
nitrogen
excretion
Introduction
Since
the
kidney
is
the
major
excretory
organ
for
metabolic
end-products,
the
rationale
of
a
nutritional
therapy
in
chronic
renal
failure
should
be
to
minimise
the
uraemic
symptoms
by
reducing
intake.
On
the
other
hand,
this
therapy
should
also
maintain
an
optimal
nutritional
status.
In
order
to
achieve
this
goal,
various
therapeutic
regimes
have
been
introduced.
Bergstrom
et
al
[1]
were
the
first
to
propose
a
diet
containing
20-30
g
of
mixed
quality
proteins,
supplemented
with
essential
aminoacids
(EAA),
including
histidine.
On
the
other
hand,
protein
restriction
is
thought
to
slow
down
the
progression
of
chronic
renal
disease,
which
is
characterised
by
progressive
glomerulosclerosis
and
tubulointerstitial
scarring.
Systemic
hypertension
[2],
glomerular
hypertrophy
[3]
and
glomerular
hypertension
Effects
of
Protein
and
Essential
Amino
Acids
on
GFR
and
Excretion
Parameters
573
[4]
are
believed
to
be
important
factors
in
the
initiation
and
progressive
nature
of
glomerulosclerosis.
In
this
pathophysiological
concept,
these
three
factors
lead
to
an
increased
glomerular
tension
with
damage
of
the
glom-
erular
endothel
line,
leading
to
an
increased
passage
of
plasma
proteins
into
the
mesangium
[5].
This
hypothesis
is
based
mainly
upon
experiments
in
rats
with
subtotal
renal
ablation
or
diabetes
mellitus.
In
humans
there
are
only
indirect
observations
for
this
concept.
In
rats,
high
protein
intake
has
been
associated
with
an
accelerated
glomerulosclerosis,
an
increasing
proteinuria
and
progressive
decline
of
GFR,
while
restricting
protein
intake
has
prevented
further
nephron
destruction
and
has
prolonged
survival
[6].
Low-protein
diet
has
been
reported
to
have
a
similar
beneficial
result
in
humans,
mainly
in
those
with
primary
glomerular
disease
[7].
Different
mechanisms
have
been
held
responsible
for
this
effect,
among
them
the
alteration
of
glomerular
haemo-
dynamics
due
to
proteins
[8].
The
question
that
therefore
arises
is
to
what
extent
EAA
influence
glomerular
haemo-
dynamics.
The
present
study
was
designed
to
investigate
the
influence
of
an
acute
protein
load
compared
to
an
acute
load
of
EAA
on
GFR
and
RPF.
A
further
aim
was
to
investigate
whether
these
changes
were
associated
with
changes
in
urinary
albumin
excretion
and
nitrogen
excretion.
Patients
and
Methods
Ten
normal
subjects,
three
women
and
seven
men
(age:
21-28
years)
were
investigated.
None
had
any
history
of
renal
disease,
diabetes
mellitus,
or
hypertension.
During
the
examination
period
they
maintained
normal
blood
pressure
and
a
negative
dipstick
of
urinary
protein
and
glucose.
All
subjects
were
studied
following
their
normal
ad
libitum
protein
diets.
As
determined
by
dietary
history,
their
protein
intake
ranged
from
0.93
to
1.27
g/day
per
kg
body-weight.
Each
subject
underwent
two
investigations
at
an
interval
of
at
least
1
week.
During
the
first
investi-
gation
the
volunteers
received
a
test
meal
of
1.4
g/kg
body-weight
of
a
protein
concentrate
(Protein
88,
Wander
Pharma
GMBH,
Nurnberg,
West
Germany).
This
con-
tained
88%
non-hydrolised
milk
proteins
(calcium
casein),
1%
fat,
various
kinds
of
vitamins,
and
was
free
of
carbohydrate.
During
the
second
investigation
they
were
given
the
same
amount
of
EAA
(EAS
oral
Granulat,
Fresenius
AG,
Oberursel,
West
Germany),
as
are
nor-
mally
used
as
a
supplement
to
a
low-protein
diet
in
our
patients
with
chronic
renal
failure.
Both
test
meals
were
ingested
over
30
min
together
with
0.5
litres
of
water.
The
composition
and
nitrogen
content
of
both
test
meals
is
given
in
Table
1.
In
a
third
set
of
experiments,
six
of
the
ten
volunteers
(one
woman,
five
men)
were
investigated,
drinking
only
0.5
litres
water
instead
of
receiving
a
test
meal
(control
group).
The
experimental
procedure
was
the
same
in
all
three
sets
of
experiments.
The
investigation
started
after
a
12-h
fasting
period.
To
achieve
a
sufficient
urinary
flow,
1000
ml
0.9%
NaCl-solution
were
infused
over
50
min
via
an
indwelling
cannula
in
the
cubital
vein
at
the
beginning
of
each
experiment.
During
the
rest
of
the
experiment
the
subjects
received
a
constant
infusion
of
250
ml
0.9%
NaCl-solution
per
hour.
After
a
priming
dose
of
inulin
(50
mg/kg
body-weight;
Inutest;
Laevosan
Gesellschaft,
Linz,
Austria)
and
PAH
(6
mg/kg
body-weight;
Nephrotest;
Lich, West
Germany),
inulin
and
PAH
were
infused
at
a
constant
rate
in
order
to
keep
the
plasma
concentration
of
inulin
between
0.2
and
0.3
mg/ml
and
of
PAH
between
0.015
and
0.025
mg/ml.
After
an
equilibrium
period
of
1
h,
two
basal
collecting
periods
of
30
min
followed.
Immediately
afterwards,
the
subjects
received
the
test
meal
with
0.5
litres
of
water
over
a
period
of
30
min.
In
the
third
set
of
experiments
the
subjects
only
drank
0.5
litres
of
water.
After
the
test
meal
there
were
three
collecting
periods
of
60
min.
Urine
was
collected
by
spontaneous
voiding.
Blood
samples
were
obtained
in
the
middle
of
each
period.
Serum
analysis
of
inulin
and
PAH
were
performed
after
protein
precipitation
with
zinc
sulphate
[9].
PAH
in
serum
and
urine
were
measured
using
the
method
of
Fritsch
[10].
Inulin
in
urine
and
serum
was
determined
using
the
Resorchin-method
[11].
The
nitrogen
content
of
the
urine
was
analysed
according
to
the
method
of
Kjeldahl.
The
urinary
albumin
concentration
was
determined
by
a
nephelometric
method
(ICS
System;
Beckman
Instruments).
Calculations
Filtration
fraction
(FF)
=
Inulin-clearance*100/PAH-
clearance
(%).
Albumin
excretion
=
albumin
concentra-
tion*urine
volume/duration
the
collection
period.
Inulin
and
PAH
clearance
were
corrected
to
standard
normal
body
surface
area
(1.73
m
2
).
Statistical
Calculations
Values
are
shown
as
mean
+
standard
deviation.
For
each
clinical
variable
mentioned
above,
statistical
analysis
of
changes
in
time
inside
one
experimental
set
and
statistical
comparison
between
the
effects
of
different
test
meals
at
different
points
of
time
was
performed
by
a
Holm
[12]
procedure.
Using
two-tailed
Pitman
permutation
tests
for
dependent
samples,
this
test
prodedure
is
based
on
all
pairwise
comparisons
between
the
effects
at
dif-
ferent
points
of
time
inside
an
experimental
set
(baseline
574
E.
Braendle
et
al
Table
I.
Composition
of
100
g
protein
concentrate
and
essential
aminoacids
(EAA)
Protein
concentrate
(g)
EAA
(g)
Glycine
L-alanine
1.8
3.0
L-valine
6.5
13.5
L-leucine
8.3
16.0
L-isoleucine
5.5
10.6
L-proline
9.9
L-phenylalanine
4.5
11.1
L-tyrosine
5.6
5.4
L-trytophan
1.5
4.2
L-serine
5.6
L-threonine
4.4
9.6
L-cystine
0.3
L-methionine
2.9
9.3
L-arginine
3.7
L-histidine
2.8
6.8
L-lysine
7.3
13.5
L-aspartic
acid
6.3
L-glutanic
acid
20.1
Nitrogen
content
16
12.8
value
0-60
min
vs
60-120
min;
60-120
min
vs
120-
180
min
after
one
load).
On
the
other
hand,
in
the
same
test
procedure
pairwise
comparisons
between
the
effects
of
different
test
meals
at
fixed
points
of
time
after
the
load
were
performed
(EAA
vs
protein
concentrate,
EAA
vs
control
group,
protein
concentrate
vs
control
group).
The
nominal
level
of
significance
for
each
multiple
test
pro-
cedure
was
chosen
to
be
alpha
=
10%.
The
advantage
of
permutation
tests
is
that
(1)
they
do
not
assume
normally
distributed
measurements,
and
(2)
they
are
more
efficient
than
other
non-parametric
tests.
Results
Inulin
clearance
(Table
2,
Fig.
1).
Inulin
clearance
increased
from
a
basal
value
of
95.8
±
8.7
ml/min
per
1.73
m
2
up
to
a
maximum
of
127.1
+
15.4
ml/min
per
1.73
m
2
in
the
second
postprandial
collecting
period
after
an
acute
protein
load. After
an
acute
EAA
load,
a
maxi-
mum
of
123.6
+
12.2
ml/min
per
1.73
m
2
was
achieved.
Comparing
both
test
meals,
no
significant
difference
was
found
between
maximal
GFR
increase
and
between
the
time
courses
of
postprandial
GFR
changes.
In
the
con-
trol
group,
inulin
clearance
increased
from
a
baseline
of
98.3
+
13.8
ml/min
per
1.73
m
2
to
a
maximum
of
102.7±
13.1
ml/min
per
1.73
m
2
in
the
first
postprandial
collecting
period.
This
increase
was
not
significant.
In
comparison
to
the
control
group,
all
postprandial
values
after
both
test
meals
were
significantly
greater.
PAH
clearance
(Table
2).
PAH
clearance
increased
after
the
protein
load
from
a
baseline
of
530
+
84
ml/min
per
1.73
m
2
to
maximum
of
710
+
68
ml/min
per
1.73
m
2
60-120
min
after
the
test
meal.
After
the
EAA
load,
PAH
clearance
increased
from
535
±
78
ml/min
per
1.73
m
2
to
735
+
81
ml/min
per
1.73
m
2
in
the
same
time.
The
differ-
ences
between
the
postprandial
values
of
both
test
meals
were
not
significant.
In
the
control
group,
PAH
clearance
increased
slightly
but
not
significantly
in
the
first
post-
prandial
collecting
period
from
a
basal
value
of
551
±97
ml/min
per
1.73
m
2
to
595
±
115
ml/min
per
1.73
m
2
.
Comparing
the
control
group
with
both
test
meals,
there
were
no
significant
differences
in
the
first
postprandial
collecting
period,
while
the
differences
in
both
the
second
and
third
postprandial
periods
were
significant.
Filtration
fraction.
No
significant
differences
were
obtained
between
pre-
and
postprandial
filtration
fraction
in
any
of
the
three
groups.
The
filtration
fraction
varied
between
16.9
+
4.3%
and
18.7
+
3.4%.
Urinary
nitrogen
excretion
(Table
2,
Fig.
1).
After
the
acute
protein
load
urinary
nitrogen
elimination
increased
continuously
and
significantly
from
a
basal
value
of
8.1
+
3.1
mg/min
to
a
maximum
of
15.4
+
3.3
mg/min
in
the
third
postprandial
collecting
period.
After
the
acute
EAA
load,
a
significant
increase
from
a
preprandial
value
of
8.7
±
1.6
mg/min
to
13.7
±
3.5
mg/min
120-180
min
after
the
test
meal
was
obtained.
In
comparison
to
the
protein
load,
the
urinary
nitrogen
excretion
was
significantly
less
after
the
EAA
load.
In
the
control
group,
nitrogen
excretion
increased
slightly,
but
not
significantly,
in
the
first
postprandial
collecting
period,
from
a
baseline
of
8.2
+
2.7
mg/min
to
9.4
±
3.9
mg/min,
decreasing
afterwards.
Urinary
albumin
excretion
(Table
2,
Fig.
1).
After
the
protein
load
urinary
albumin
excretion
increased
signifi-
cantly
in
the
first
postprandial
collecting
period
from
a
basal
value
of
4.4±
1.9
tig/min
to
13.5
+
4.7
µg/min,
decreasing
afterwards
to
a
final
value
of
8.3
±
2.3
µg/min
in
the
last
postprandial
collecting
period.
The
values
of
the
third
postprandial
period
were
significantly
greater
than
those
of
the
preprandial
period.
After
the
EAA
load,
urinary
albumin
excretion
also
increased
significantly
in
the
first
postprandial
period
from
a
baseline
of
4.8±
1.7
µg/min
to
14.4
+
5.4
µg/min.
Afterwards,
albu-
min
excretion
decreased
continuously
to
a
value
of
7.8
±
3.2
µg/min.
This
value
was
significantly
greater
than
the
preprandial
one.
In
the
control
group
urinary
albumin
excretion
increased
significantly
from
a
preprandial
value
of
5.0
±
1.9
µg/min
to
a
maximum
of
11.6
+
5.1
µg/min
in
the
first
postprandial
period.
In
the
following
period,
albumin
excretion
declined
continuously
to
a
final
value
of
4.8
±
1.9
µg/min.
Albumin
excretion
in
the
first
and
third
postprandial
collecting
periods
after
both
test
meals
was
significantly
greater
than
in
the
control
group.
No
significant
differences
were
found
in
the
postprandial
albumin
excretion
between
both
test
meals.
Diuresis
(Table
2,
Fig.
1).
After
the
protein
load
diuresis
increased
significantly
from
a
basal
value
of
C
hang
e
fro
m
bas
a
l
va
lues
(
'6)
Effects
of
Protein
and
Essential
Amino
Acids
on
GFR
and
Excretion
Parameters
Table
2.
Inulin-,
PAH-clearance,
albumin
excretion,
nitrogen
excretion
and
diuresis
after
an
acute
oral
load
of
1.4
g/kg
body-
weight
EAA
or
proteins
Basal
Basal
0-60
min
60-120
min
120-180
min
575
Inulin
clearance
(ml/min
per
1.73
m
2
)
Protein
95.8+8.7
n.s.
97.2+9.6
EAA
99.1±10.7
n.s.
95.6±
11.2
Control
98.3
+13.8
n.s.
96.7
±
12.1
PAH
clearance
(ml/min
per
1.73
m
2
)
Protein
530±84
n.s.
542
±
57
EAA
535±78
n.s.
561
±
87
Control
551
+97
n.s.
531
+99
Urinary
albumin
excretion
(µg/min)
Protein
4.4±1.9
n.s.
4.7
±1.5
EAA
4.8+1.7
n.s.
5.1+
1.8
Control
5.0±1.9
n.s.
4.6±1.7
Urinary
nitrogen
excretion
(mg/min)
Protein
8.1
+
3.1
n.s.
8.3
+
1.7
EAA
8.7+
1.6
n.s.
8.4
+2.4
Control
8.2±2.7
n.s.
7.9
+
2.5
Diuresis
(ml/min)
Protein
1.6+1.4
n.s.
1.8±1.2
EAA
1.4±1.0
n.s.
1.7
±
1.3
Control
1.3+1.2
n.s.
1.9
±
0.8
s.
s.
109.9±12.3
112.3
±10.2
s.
s.
127.1
+
15.4
123.6
±
12.2
s.
s.
114.9+13.9
110.8±8.8
n.s.
102.7±
13.1
n.s.
100.7
±
16.2
n.s.
97.2
±12.6
s.
607
±
70
s.
710
±
68
s.
615
±80
s.
616
±
74
s.
735±81
s.
604
±
91
n.s.
595±
115
n.s.
579±
124
n.s.
546±82
s.
13.5±4.7
s.
10.5
±
3.4
s.
8.3±2.3
s.
14.4+5.4
s.
11.9+4.8
s.
7.8
+3.2
s.
11.6±5.1
n.s.
9.2
+
3.7
s.
4.8±1.9
s.
12.8
±2.9
n.s.
13.4
+
2.5
s.
15.4±3.3
n.s.
10.8
+3.7
n.s.
11.2
±
3.4
s.
13.7
±
3.5
n.s.
9.4±3.9
n.s.
8.9
±
3.1
n.s.
8.6
±2.8
s.
5.4+2.2
n.s.
5.3
±
2.3
s.
3.5
±1.6
s.
5.2
±
2.9
n.s.
5.0
+
2.6
s.
3.2
±
1.7
s.
3.8±2.6
n.s.
4.0
±
2.8
n.s.
2.8±2.4
In
the
control
group
(control),
these
parameters
are
shown
after
an
acute
water
load.
Using
two-tailed
Pitman
permutation
tests,
pairwise
comparisons
of
the
effects
at
different
time
before
and
after
the
administration
of
the
load
were
performed
(basal
value
vs
basal
value,
basal
value
vs
0-60
min,
0-60
min
vs
60-120
min,
60-120
min
vs
120-180
min).
S.
(=significant)
respectively
n.s.
(=
not
significant)
is
related
to
a
nominal
multiple
level
of
significance
of
alpha
=10%
for
each
test
(see
also
Methods).
Control
group
Protein
load
EAA
load
250
Inulin
clearance
o
Nitrogen
excretion
I
200
Albumin
excretion
r
-
-c
I
*
o
Diuresis
IT\
\
I
i
\
Ii
\
i
f
\
150
\
ik
1
i '
\
\
I
i
i‘
\
II
Ii
t\
Ii
\
100
If
.
ti
\
b
\
q
a
f
‘.
‘,
I
Ii
%
....
cr
Ail
No
f
\
sr
.
1
\
1
-.
1
.-•
50
-
i
.1
.
%.
i
/ ,
-'•
..0.
.
:::::11::,
4
--
0
4
-
4
-4
1
-
,.11.
.
-4
-
2
-;-
.24
1--
9
-
4
-
-,
e
-
1
'".
9
4
,--
.
b
b
60
120
180
b b
60
120
180
b b
60
120
180
Time
(min)
Time
(min)
Time
(min)
Fig.
I.
Inulin
clearance,
nitrogen
excretion,
albumin
excretion,
and
diuresis
after
an
acute
oral
load
of
1.4
g/
kg
body-weight
EAA
or
proteins
in
comparison
to
an
oral
water
load
(control
group)
b,
basal
collecting
periods
of
30
min
before
the
test
meal;
60
min,
120
min,
180
min
indicate
the
time
after
the
test
meal.
576
E.
Braendle
et
al
1.6±
1.4
ml/min
to
a
value
of
5.4
+
2.2
ml/min
in
the
first
postprandial
period,
declining
afterwards
to
a
final
value
of
3.5
±
1.6
ml/min.
After
the
EAA
load
diuresis
increased
from
1.4±
1.0
ml/min
to
5.2
+
2.9
ml/min.
In
the
last
period
diuresis
was
3.2
±
1.7
ml/min.
In
the
control
group
diuresis
also
increased
significantly
from
a
basal
value
of
1.3±
1.2
ml/min
to
4.0
+
2.8
ml/min
in
the
first
postpran-
dial
period,
declining
to
a
final
value
of
2.8
+
2.4
ml/min.
Comparing
the
test
meals
to
the
control
group,
the
values
of
both
test
meals
during
the
first
and
second
postprandial
collecting
periods
were
significantly
greater,
while
in
the
third
period
the
differences
between
these
groups
were
not
significantly
different.
The
differences
between
both
test
meals
during
all
postprandial
periods
were
not
significant.
Discussion
In
this
study
we
demonstrated
how
an
acute
load
of
EAA
increase
both
glomerular
filtration
rate
and
renal
plasma
flow
to
the
same
extent
as
an
acute
oral
load
of
proteins..
The
same
results
were
obtained
in
studies
with
5/6
nephrectomised
rats
[13].
In
our
results
the
maximal
increment
was
observed
60-120
min
after
both
meals.
The
postprandial
values
obtained
after
120-180
min
were
significantly
less
than
those
after
60-120
min.
The
same
amount
and
same
time
course
of
changes
in
glomerular
filtration
rate
were
obtained
by
other
authors
using
aminoacids
solutions
or
protein
concentrates
as
an
acute
oral
load
[14,15].
On
the
other
hand
the
time
course
of
changes
in
glomerular
fil-
tration
rate
seem
to
be
different
if
red
cooked
meat
is
used
as
an
acute
oral
load.
The
glomerular
filtration
rate
sig-
nificantly
increased
60
min
after
the
load
of
red
cooked
meat,
remaining
at
that
level
for
more
than
2
h
[14,16].
A
possible
explanation
for
this
different
time
course
could
be
the
slower
digestion
and
resorption
of
red
cooked
meat.
Nevertheless,
other
factors
may
also
play
a
role.
The
physiological
mechanism
involved
in
the
increase
in
glomerular
filtration
rate
after
an
acute
protein
load
is
still
unknown.
Our
results
suggest
that
the
amount
of
nitrogen
consumed
as
well
the
urinary
nitrogen
excretion
is
not
responsible
for
the
increase
in
glomerular
filtration
rate.
The
following
facts
support
this
suggestion:
Inulin
and
PAH
clearance
increased
to
the
same
extent
after
both
test
meals,
although
(1)
The
amount
of
nitrogen
consumed
was
less
with
EAA
than
with
proteins;
(2)
urinary
nitrogen
excretion
after
the
EAA
load
was
signifi-
cantly
less
than
after
the
protein
load;
and
(3)
in
the
third
postprandial
collecting
period,
glomerular
filtration
rate
decreased,
while
nitrogen
excretion
still
increased.
The
increase
in
urinary
nitrogen
excretion
is
caused
mostly
by
a
greater
production
and
elimination
of
urea
after
ingestion
of
proteins
or
aminoacids
[17].
In
this
way,
a
similar
finding
was
observed
by
O'Connor
and
Summerill
[18]
in
dogs.
They
demonstrated
that
feeding
urea
in
quantities
equivalent
to
those
produced
by
a
stan-
dard
meal
could
not
reproduce
the
acute
GFR
elevation
induced
by
meat
meal.
Glucagon
is
thought
to
play
an
important
role
as
a
mediator
in
protein-
or
aminoacid-induced
glomerular
hyperfiltration
[19,20].
Rocha
et
al
[21]
showed
that
cer-
tain
aminoacids
stimulate
the
secretion
of
glucagon
to
a
different
degree
in
dogs.
Although
according
to
Rocha
et
al,
EAA
(with
the
exception
of
phenylalanine)
have
the
least
glucagen-stimulating
activity,
in
our
experiments
EAA
increased
glomerular
filtration
rate
to
the
same
extent
as
a
mixture
of
aminoacids
with
a
greater
glucagon-
stimulating
activity.
On
the
other
hand,
Dhaene
et
al
[22]
demonstrated
a
greater
increase in
glomerular
filtration
rate
after
red
cooked
meat
than
after
an
aminoacid
solution
with
the
same
composition
as
red
cooked
meat,
except
for
glycine
and
alanine.
With
respect
to
this
hypothesis
that
both
these
aminoacids
play
a
special
role
in
the
protein-induced
hyperfiltration,
it
is
important
to
note
that
in
our
exper-
iments
EAA
increased
glomerular
filtration
rate
to
the
same
extent
as
proteins,
although
EAA
did
not
contain
glycine
and
alanine.
Therefore,
besides
these
suggested
mechanisms,
others
have
to
be
discussed.
A
significant
postprandial
increase
in
urinary
albumin
excretion
was
noticed
in
all
three
sets
of
our
experiments,
associated
in
all
cases
with
increased
urinary
flow.
Viberti
et
al
[23]
showed
that
increased
diuresis
leads
to
an
augmentation
of
albumin
excretion
after
both
the
acute
and
chronic
water
load,
and
this
was
observed
only
during
the
first
90
min
after
the
load.
This
observation
is
in
accordance
to
our
data.
In
the
control
group
albumin
excretion
decreased
to
normal
values
again
120-180
min
after
the
water
load,
although
diuresis
was
still
increased.
Therefore
we
think
that
most
of
the
increase
in
urinary
albumin
excretion
that
we
observed
in
both
the
first
and
second
postprandial
collecting
periods
was
due
to
an
increased
diuresis.
Besides
the
increase
in
diuresis,
other
mechanisms
may
play
a
role
by
increasing
albumin
excretion
after
both
test
meals.
In
contrast
to
the
control
group
albumin
excretion
after
both
test
meals
was
still
elevated
in
the
third
post-
prandial
collecting
period,
during
which
no
significant
difference
in
diuresis
was
found
between
these
groups
and
the
control
group.
This
increase
in
albumin
excretion
during
the
third
postprandial
collecting
period
after
both
test
meals
can
not
be
explained
by
increased
diuresis,
because
our
data
and
these
of
Viberti
et
al
[23]
show
that
albumin
excretion
is
no
longer
influenced
by
diuresis
in
the
third
postprandial
collecting
period.
We
therefore
need
to
consider
other
additional
mechanisms
for
the
increase
of
urinary
albumin
excretion
after
the
test
meals.
One
possibility
could
be
a
decreased
tubular
reabsorp-
tion
of
albumin
due
to
an
increase
of
glomerular-filtered
Effects
of
Protein
and
Essential
Amino
Acids
on
G
FR
and
Excretion
Parameters
577
aminoacids.
Mogensen
et
al
[24]
showed
that
after
intra-
venous
administration
of
aminoacids,
urinary
albumin
excretion
and
B
2
-microglobulin
excretion
increased
in
dose-dependent
manner.
They
suggested
that
these
increases
are
due
to
an
inhibition
of
tubular
reabsorption
of
these
proteins.
On
the
other
hand,
Rafoth
et
al
[17]
showed
that
after
ingestion
of
protein
the
plasma,
amino-
acid
concentration
increased
in
a
dose-dependent
manner.
Therefore
it
could
be
assumed
that
after
a
test
meal
the
greater
plasma
aminoacid
concentration
increased
urinary
albumin
excretion
by
the
same
mechanism
suggested
by
Mogensen
et
al.
On
the
other
hand,
Soiling
et
al
[14]
and
Chan
et
al
[25]
did
not
observe
an
augmentation
of
urinary
albumin
excretion
after
an
acute
protein
load.
But
it
is
noticeable
that
Soiling
observed
an
increase
in
B
2
-microglobulin
excretion
and
Chan
a
significant
increase
in
urinary
IgG-
immunoglobulin
excretion
after
the
test
meal.
A
possible
reason
why
the
authors
were
not
able
to
observe
an
augmentation
of
the
urinary
albumin
excretion
may
be
a
dose-dependent
problem.
Alternatively,
changes
in
glomerular
filtration
of
albumin
due
to
an
acute
protein
load
could
also
be
responsible
for
a
postprandial
increase
in
urinary
albumin
excretion.
Chan
et
al
[25]
observed
no
change
in
glomeru-
lar
size
selectivity
after
an
acute
load,
but
the
mechanism
by
which
an
acute
protein
load
modifies
urinary
albumin
excretion
cannot
be
deduced
from
this
experiment.
There
are
only
a
few
preliminary
studies
in
which
supplemented
diets
have
been
compared
with
unsupple-
mented
protein
restriction
as
regards
their
effect
in
reducing
the
progression
of
chronic
renal
failure
[26-28].
In
these
studies
the
supplemented
diet
seems
to
be
more
effective
in
slowing
the
progression
of
chronic
renal
failure,
with
the
caveats
that
the
observation
periods
in
these
studies
were
too
short,
and
that
the
nitrogen
intake
differed
in
the
compared
group.
Micropunction
studies
of
protein
restriction
in
the
remnant
rat
kidney
model
offered
evidence
that
haemo-
dynamic
changes
(due
to
changes
in
glomerular
arteriolar
resistance
and
changes
in
glomerular
ultrafiltration
coef-
ficient)
can
be
held
responsible
for
the
beneficial
effect
of
low-protein
diet
on
slowing
the
progression
of
chronic
renal
failure
[29].
Therefore
one
rationale
of
this
study
was
to
test
the
haemodynamic
effect
of
EAA
in
comparison
to
proteins.
This
rationale
was
supported
by
the
data
of
Rocha
et
al
that
EAA
have
a
lesser
capacity
to
stimulate
glucagon.
However,
when
haemodynamic
effect
was
tested
in
the
form
of
an
acute
load,
we
were
unable
to
observe
any
significant
differences.
References
1.
Bergstrom
J,
Fiirst
P.
Noree
L-O.
Treatment
of
chronic
uremic
patients
with
protein-poor
diet
and
oral
supply
of
essential
amino
acids:
1.
Nitrogen
balance
studies.
Clin
Nephrol
1975;
3:
187-194
2.
Baldwin
DS,
Neugarten
J.
Blood
pressure
control
and
progression
of
renal
insufficiency.
In:
Mitch
WE,
Brenner
BM,
Stein
JH,
eds.
The
Progressive
Nature
of
Renal
Disease.
Churchill
Livingstone
Inc,
New
York,
1986:
81-110
3.
Yoshida
Y,
Fogo
A,
Ichikawa
I.
Glomerular
hypertrophy
has
a
greater
impact
on
glomerular
sclerosis
than
the
adaptive
hyperfunction
in
remnant
nephrons.
Kidney
Int
1988;
33:
327.
(Abstract)
4.
Anderson
S,
Meyer
TW,
Rennke
HG.
Brenner
BM.
Control
of
glomerular
hypertension
limits
glomerular
injury
in
rats
with
reduced
renal
mass.
J
Clin
Invest
1985;
76:
612-619
5.
Rennke
HG.
Structural
alterations
associated
with
glomerular
hyperfiltration.
In:
Mitch
WE,
Brenner
BM,
Stein
JH,
eds.
The
Progressive
Nature
of
Renal
Disease.
Churchill
Livingstone
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Received
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Accepted
in
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2.4.90