of the American. Society of Nephrology. 1145. Penal Functional. Reserve in Kidney and Heart Transplant. Jean-Louis. Ader,3. Ivan Tack, Dominique. Durand,.
Penal
Functional
Jean-Louis
Ader,3
Jean-Michel
Ivan
Reserve
Tack,
in Kidney
Dominique
Durand,
Tuan
and
Tran-Van,
A D.
Durand,
et
T. Tran-Van, Laboratoire R#{233}nales and Unite Hospital, Toulouse,
L. Rostaing.
J.-M.
Transplantation.
Toulouse,
Suc,
Explorations INSERM 388. France
Soc.
Service
Rangueil
de
Nhrolo-
University
Hospital,
1 99#{243}; 7: 1 145-1 152)
Nephrol.
ABSTRACT Renal
functional
seems
less severe
recipients
(RFR),
paradoxically often in heart-transplant when
therapy.
elicited
infusion,
than
HTR, respectively)
to cyclosporine
submitted
acid
impairment in kidney
(KTR and
reserve
by
Renal
a 3-h
was examined
both
are
functional
intravenous
amino
in 12 KTR and
13 HTR at 7
to 8 months, eight one-kidney
appropriately compared with either or 12 two-kidney healthy control
subjects was 54
and
Baseline GFR 4 mL/min in HTR (P < 0.05). During amino acid infusion, the maximum increase in GFR (which represented RFR) was 1 7 ± 3 mL/min in both KTR and HTR (P < 0.001). RFR in KTR was
(1K.C
±
2K.C,
4 mL/min
96
± 18% of that
59
±
respectively).
in KTR and
71
in 1K.C, whereas
±
RFR in HTR was
only
9% of that
in 2K.C. Effective RPF increased (41 ± 8 mL/min, P < 0.001), and renal vascular resistances decreased (48 ± 17 mm Hg/L per mm, P < 0.05) in KTR but not in HTR. These results demonstrate that both KTR and HTR possess a renal reserve but that the single renal graft in KTR retains a proportionally higher baseline GFR and a better ability to exhibit a RFR than the two native kidneys in HTR. This dissimilar impairment
could
result from
activation
slightly
of the
intact
higher renal
accentuated by cardiac quences of former heart ations
in the
prevalence HTR. Key
Words:
amino Received 2
ThIs
3
acid
cardiac
cyclosporine sympathetic
graft
function,
and
have
consistently
graft
function
and
Renal
transplantation,
infusion,
January
renal
quenthy appraisal
of Nephrology,
San Diego. to Dr. i-I.
1, Avenue
28th
reciprocal
serum
relation
( 1 6).
This
in addition observation
Lab. Explorations
spective
ability
functional Renal
reserve. functional
difference
between
degree
in
Poulh#{232}s,31054
Toulouse
1046.6673/0708-1145503.00/0
of the American Society of Nephrology 0 1996 by the American society of Nephrology
of the
American
Society
of Nephrology
Cedex,
France.
stable
results
and
slopes
of
of the
creatinine the
of KTR
to
and
evolutions
time
in HTR
and
nephrons
elicited
the latter. This further the re-
HTR
to
demonstrate
is
defined
(RFR)
by vasodilation
play
because
the
reduction
may
imply
lesion
the has
been
have a both
a major
role
deterioration
or the that
at maximum that such a relentless toward
renal
though
and HTR attention
functional
reserve
primary
and
of glomerular
KTR deserves
hemodynamics
working
the
GFR
by stimuli such as oral and/or dopammne infusion renal capacity to achieve a
issue of whether and a RFR
renal
a as
or “unstimulated
of function
are
RFR
in
reserve
basal
substantial evidence tration may induce tion and a progression
Even
injury, examine
and
cyclosporine-induced
of the R#{233}nales,
between
“stimulated” GFR increased protein load or amino acid ( 1 7-2 1 ). RFR reflects the
altered
Fonctionnelles
serum
to immunologic prompted us
because
of the American
quite
and in paradoxical because it could have been assumed reasonably that the renal function of two native kidneys in the former would be better preserved than that of one grafted kidney, submitted
higher
8, 1995.
values,
reciprocal
discrepancy KTR is a priori
and/or
cyclosporine
but contrast,
to cardiac transplantathe frequent occurrence of in renal function not infre-
creatinine
between
higher
in
in
on indirect comparison of results from studies that have been carried out separately either in kidney or in heart transplant recipients (KTR and HTR, respectively). To our knowledge, In only one study so far has renal function in KTR and HTR been compared directly, and then only by using serum creatinine levels,
The response
27, 1996. Annual Meeting
CA, November
Ader. Jean
March
at the
contributed
leading to insufficiency (8-15). The dissimilar of renal function is almost exclusively based
arterioles. normal
therapies
has
impaired
whereas,
studies in patients submitted tion have rather suggested a progressive deterioration
consealter-
transplantation.
hemodynamics,
22, 1996. Accepted In part
cardiac
described
renal potential
additive
therapy
( 1-7),
functional
H#{244}pltalPangueil,
Journal
immunosuppressive
(22,23)
correspondence
Journal copyright
dosage, innervation
denervation, failure and
of hypertension
study was presented
Society
Rostaing,
to prolonged allograft and patient survival rates, concerns have grown about the evolution of renal function, caused by, among other things, the side effects ofcyclospormne, the most important ofwhich is impairment of renal function and, possibly, progressive renal insufficiency. It Is noteworthy that studies evaluating the evolution of renal allograft function
France
(J. Am.
Lionel
Transplant
Suc
J.-L. Ader. I. Tack, Fonctionnelles Rangueil University
gie
Heart
absence
the
capacity.
of
residual
There
is
a glomerular hyperfildecline in renal funcrenal failure regardless
( 17,24).
persistence previously
of
an
amino
examined
(25-29), all of the aforementioned evaluations have been performed only in baseline conditions,
acidin
KTR
in HTR and
1145
RFR in Kidney
and
Heart
Recipients
and
RFR has neither been investigated nor compared with that in KTR. Therefore, the aims of this study were to determine whether RFR is still present in KTR and in HTR, both at similar times after transplantation, and appropriately compared with either one-kidney or two-kidney healthy control ( 1 K.C and 2K.C, respectively) subjects.
study
(previously
Centre
Hospitalier
was
carried
out
phrectomized
approved
by the
ethical
Universitaire
in 12 KTR, subjects
de
13 HTR,
(1K.C),
eight
and
review
12
volunteers
was
HTR were
immunosuppressive thioprine. and first
days
globulins
after
transplantation
atinine high
level had cyclosporine
justed
were
in
both
thereafter to
(6
SP kit’; during
KTR
in HTR.
less mg/kg
and
cadaveric
grafts
duration
of
7.6
renal
and
to
it was
and
five
0.4
months
graft
cold
rejection
than per
by
therapy,
levels. chronic tation,
according a course
with
There
female;
rejection serum
no
8
crc-
was
creatinine
one
and one (Grade
values
7.2
±
returning
were
Mean 1 h. Two
2 yr after 124
and
or
to
moderate
levels
were
1 ). HTR had higher than
both
Prednisone 0
b C
d e
Dosage
(mg/kg
per day)
consid-
mean was 2).
brought
(N functional
patients
in
about
5) cardiomyop-
=
impairment
the
which
one
course
the
rejection
and two to four Endomyocardial rejection
time
slightly
ventricular
of
but
of
their
episode
rejection biopsies
that
was
the
study,
serum
in 2K.C,
and
oc-
episodes showed
reversed
with
as assessed by normalwithout requiring OKT3 daily
significantly
a normal
ejection
azathioprine
those in KTR, cyclosporine
higher
creatinine
a good
sive
fraction
than
in KTR
level,
although
graft
function
cardiac
higher
of 13 recipients
therapy
with
(LVEF)
and higher considered
significantly
2). Twelve
control
and
than
that
were
stable
was
63.6
1.4%
±
than 60% in all patients except to be hypertensive, and mean of 1 K.C
maintained
doses
of
subjects
a
and
2K.C
(Table
on antihypertenCCA,
either
alone
(1 K.C),
HTR
8
2K.C
13
12
52.1 67.6 1.74
±
2.1
54.2
±
3.9
50.5
±
3.Ob
27.8
±
1.5
±
2.8
66.0
±
4.4
77.5
±
2#{149}6b
60.3
±
2.3
±
0.04
0.06
O.03
±
0.04
±
3
± ±
4
15
±
8 1 1
±
13 18 3.0 125
5 3
±
±
0.8
±
0. 1 18 0.1 0.02
1.85 107 24 14 3.9 170 0.9 0.19
±
±
1.73 98 13
±
109
0.20
±
±
±
or
of maintenance
1K.C
KTP
per day)
aza-
normal
as assessed serially by echocardiography. Left ventricular end-diastolic diameter was smaller than 55 mm, and fractional shortening was higher than 30% in all patients. Mean
12
(mg/kg
failure
idiopathic renal
pulse therapy score 2 wk later, At
immunosuppressive regimena
Dosage
the
cellular
.
Azathioprine
were
group of recipients 1K.C and 2K.C (Table
heart
during
prednisolone of biopsy
AP was
.tmol/L,
Number
of
months,
TABLE 1 Characteristics of kidney-transplant recipients (KTP), one-kidney heart-transplant recipients (HTR), and two-kidney control subjects (2K.C),
Age (yr) Body Weight (kg) Body Surface Area (m2) Serum Creatinine (,.mol/L) Plasma Penin (ng/L) Plasma Aldosterone (ng/dL) Cyclosporine Dosage (mg/kg per day) Blood Cyclosporine Level (ng/mL)
the whole that of
in seven recipients, in four recipients.
(range, 51 to 70%) one. All HTR were
baseline
Characteristic
of than
any
(Table
left
were pulse
transplan1 16
0.2
it was 2
acute
mL/min,
including
and prednisone dosages were similar to whereas cyclospormne dosage and whole-blood
in another I or II acute
to
57 patients
regimen
of Intractable
in
administration.
100
recipient
of subsequent
±
methyl ization
received
Rejections prednisolone
recipients:
levels
26 in
detected
curred occurred
level to
studies.
because
mild
same
1 ) had
the
occurred
evidence two
the
Table
ischemia
creatinine
in these
to
initial then ad-
to decrease
before
episodes
been
mol/L; was
maintain
to Banff classification). of 3 days of methyl
serum
has
5
concentration
allowed
and 4 months after transplantation, recipient 7 months after transplantation rejections reversed
175 day)
azathe
serum
cyclosporine
HTR
±
cyclosporine
recipient’s
(AP)
and all
cardiac disease before transplantation; serum creatinine level and creatinine clearance rate were 108 ± 5 .tmol/mL and 80 ± 7 mL/min, respectively, 1 wk before heart grafting. The average time between transplantation and the study was
Incstar Co. Stillwater, MN) to reach the first 6 months after transplan-
whereas
150 ng/mL in KTh. All KTR (seven male
biopsy-proven
to
each
sequential
prednisone, globulins during
for
when
to whole-blood
(RIA, Cyclo-Trac, 150 to 200 ng/mL tation
switched
decreased dosage
according
to a quadruple
regimen, comprising antithymocyte
polyclonal
days
submitted
63
study,
and cyclosporine and had (Table 1 ). Six of 1 2 KTR were hypertensive, and baseline
by either ischemic (N = 8) or athy (Table 1 ). No noticeable
(2K.C).
All KTR and
were the
maintenance
higher
recipients
unine-
healthy
pressure
of
Hypertensive KTR were maintained on monotherapy with stable doses of a calcium channel antagonist (CCA). Neither plasma renin nor aldosterone levels differed between KTR and 1K.C or 2K.C (Table 1). Heart transplantation had been performed in 13 male
France)
previously
rates
time
a triple-drug
arterial significantly
board
Toulouse,
the
thioprine, prednisone, serum creatinine levels ered to be moderately
Subjects The
clearance At
receiving
METHODS
of the
creatinine
respectively.
±
5
1.69 78 12
±
2
15
±
02d
±
1 ic 0.1 0.03
± 3b
±
±
±
2 2
Values are means t SE. p < 0.001 for HTR versus 2K.C. p < 0.01 for HIP versus 2K.C. p - 0.01 for HIP versus KTP. p < 0.05 for HIP versus KTR.
1146
Volume
7
‘
Number
8
‘
1996
Ader
TABLE 2. Effects of amino acid infusion (Stimulation) on mean arterial pressure (AP), effective renal plasma flow (ERPF), and filtration fraction (FF) in graft recipients and control subjectsa Stimulation
Baseline
A second 0.9%
After
of
flow
urine
7.4%
90±5
102
240 ± 20 346 ± 37 307 ± 21C 533±31
281
357
1K.C HTR
23.5 21.8 23.6
2K.C
21.3
25.4 27.2 28.7 25.0
1K.C HTR 2K.C KTR
C
e
a h
103 ± 3 78±2
±
i4
234
±
38
321
78±2
± 43 297 ± i3 515±16
312 ± 2iC 584±29
2.0 1.7 1.2 0.9
± ± ± ±
±
2.0
±
27g
±
1.6’ 1.2
±
23.8 23.9 22.7 22.4
± ± ±
versus respective 0.01 versus respective 0.05 versus respective
p
<
