Open Journal of Organ Transplant Surgery, 2011, 1, 14-18
doi:10.4236/ojots.2011.12003 Published Online November 2011 (http://www.SciRP.org/journal/ojots)
Copyright © 2011 SciRes. OJOTS
Combined Heart-Kidney Transplantation: A Single Center
Experience
Giuliana Bacchi1, Luciano Potena2, Giovanni Mosconi1, Candida C. Quarta2, Lucia Stalteri1,
Gaia Magnani2, Giorgio Feliciangeli1, Francesco Grigioni2, Angelo Branzi2, Sergio Stefoni1
1Department of Internal Medicine, Aging and Renal Disease, University of Bologna, Bologna, Italy
2Cardiovas cular De p a r tment, heart transplant program, University of Bologna, Bologna, Italy
E-mail: giuliana.bacchi@unibo.it
Received August 26, 2011; revised October 1, 2011; accepted October 12, 2011
Abstract
Introduction: We report our experience with seven cases of combined heart-kidney transplantation (HKT).
Patients and methods: Between January 2003 and December 2009, seven subjects underwent combined HKT,
receiving both organs from a single donor. Their age ranged from 30 years to 59 years, six were male. Five
patients were dialysis dependent before transplantation and two were in chronic renal failure (serum crea-
tinine levels > 2.6 mg/dL). The heart was transplanted first in all cases. Results: Heart function rapidly
re-covered in five of the patients, while two needed temporary inotropic and mechanical support. Diuresis
started immediately in four patients. At discharge, all patients had well-functioning grafts (left ventricular
ejection fraction 60% ± 6%; serum creatinine 1.4 ± 0.3 mg/dL). After an average follow-up period of 45 ± 24
months no deaths have occurred. Heart allografts are functioning normally in six patients and none of the
patients currently require dialysis treatment. The main adverse event noted during follow-up was hyperten-
sion in five patients. Four patients were cardiac allograft rejection free and five patients were kidney rejec-
tion free. Conclusion: Our results are in line with the data which has been previously reported in the litera-
ture and suggest that HKT is a viable therapeutic choice in the treatment of advanced cardiac and renal fail-
ure in carefully selected patients.
Keywords: Heart Transplantation, Kidney Transplantation, Dual-Organ Transplantation, Heart Failure,
Kidney Failur e
1. Introduction
Since the first report of a combined heart and kidney
transplant (HKT) from a single donor in 1978 [1], and
following the subsequent successful HKT in terms of
long term survival in 1986 [2], this therapeutic solution
has been performed numerous times and with growing
frequency with more than 722 such procedures reported
to the United Network for Organ Sharing (UNOS) be-
tween January 1, 1988 and May 31, 2011.
Herein, we report our experience with 7 patients who
underwent combined HKT.
2. Methods
Between January 2003 and December 2009, 533 kidney
transplantations and 243 heart transplantations were per-
formed at the S. Orsola Uni versity Hospital. Among these,
seven subjects underwent combined heart and kidney
transplantations (HKT), receiving both organs from sin-
gle donors selected acco rding to ABO blood group com-
patibility and a negative lymphocytotoxic cross-match,
but without regard to HLA-antigen matching due to the
time constraints of cardiac surgery. One other patient, in
addition to a heart and kidney, received a liver and so
was not considered in this report. A retrospective review
of the medical records of these 7 HKT recipients was
conducted.
The surgical technique did not differ from the one
used in the isolated transplantation of these organs.
In six cases, the heart transplant was performed and
then the renal allograft was positioned immediately af-
terwards. In one case (no. 3), the kidney was implanted
ten hours after the heart wh en the hemodynamic situation
of the patient had sta bil i zed.
Patients were followed up by both transplantation teams,
15
G. BACCHI ET AL.
and surveillance did not differ from that of recipients of
isolated organs.
Coronary angiography and echocardiography exami-
nations were performed at regular intervals to assess
heart function. For the surveillance of cardiac allograft
rejection, endomyocardial biopsy was routinely per-
formed once a week during the first month, bimonthly
for the next 2 months, monthly for the next 3 months,
every two months during the six to twelve month period
after transplantation, quarterly for the second year and
twice a year thereafter. Acute heart rejection was his-
tologically graded according to the international society
of heart and lung transplantation classification (ISHLT).
For the kidney, function was generally checked month -
ly by means of blood and urine tests; duplex Doppler
ultrasonography was performed every 4 months - 6 mon-
ths. Renal rejection was suspected upon biochemical
parameters and by means of the Doppler ultrasonogr aphy
resistance index perfusion scan technique. Renal biopsy
was not performed routinely but only in the case of a
persistent compromise of renal function. Biopsy was
performe d in one pat i e nt (no. 7).
Immunosuppression: all patients were treated accord-
ing to the protocols for immunosuppressive therapy in
heart transplant recipients, consisting in induction with
rabbit anti-thymocyte globulin (rATG), (Thy moglobu lin e,
Genzyme; Ireland), followed by maintenance therapy
with cyclosporine, steroids and azathioprine (no.1 - no.3)
or mycophenolate mofetil (no. 4 - no. 7). Rejection was
treated with pulse intravenuous steroids or with intrave-
nous rATG if hemodynamic compromise was present.
3. Results
Patient characteristics are summarized in Table 1. Pa-
tient age ranged from 30 years to 59 years with a mean
of 40.5 years ± 10.3 years, all of the recipients were male
except for one female. Five patients had a normal body
mass index, one was overweight and the female was un-
derweight. The etiology of the end-stage heart failure
was idiopathic cardiomyopathy in four patients, hyper-
trophic cardiomyopathy in two, and ischemic cardio-
myopathy in one. This latter patient had previously un-
dergone valvular cardiac surgery. Each patient had se-
vere, fixed impairment of systolic cardiac function with
an average left ventricle ejection of 27% ± 10%.
Five patients had irreversible end-stage renal failure
managed by dialysis with a mean time on dialysis of 55
months ±63 months. The other two were suffering from
chronic renal failure with serum creatinine levels >2.6
mg/dL.
Donor and allograft ischemic times are shown in Ta-
ble 2.
Six of the donors were male and were aged between
17 and 60 (mean age 30 years ± 18 years). The mean
ischemic time was 160 minutes ± 14 minutes for the
Table 1. Patient demographics, clinical characteristics at the time of transplantation.
Pt no. Age Sex Body Mass Index Heart diseaseLVEF (%)Cardiax index
(L/min/m2) Kidney disease Dialysis type Time on
Dialysis months
1 59 M 26 ICM 23 2.23 VA 2.6* -
2 32 M 23 IDCM 20 1.79 GN HD 1
3 49 M 22 HCM 29 1.91 IN PD 11
4 38 F 17 HCM 48 3.31 IN HD 23
5 34 M 20 IDCM 28 2.92 VA 3.1* -
6 30 M 25 IDCM 20 4.58 GN HD 92
7 42 M 20 IDCM 21 1.16 ADPKD HD 148
*Serum creatinine levels. ADPKD, autosomal dominant polycystic kidney disease; GN, chronic glomerulare disease; HCM, hypertrophic cardiomyopathy; HD,
hemodialysis; ICM, ischemic cardiomyopathy; IDCM idiopathic dilatative cardiomyopathy; IN, chronic interstizial nephritis; LVEF left ventricular ejection
fraction; PD, peritoneal dialysis
Table 2. Donors and allograft ischemic time.
Pt no. Donor age Donor sex Heart ischemic time minut e sKidney ischemic time hours Cross-mat c h
1 18 M 180 10 negative
2 16 M 170 10 negative
3 31 M 145 20 negative
4 60 F 170 11 negative
5 17 M 144 9 negative
6 20 M 164 10 negative
7 49 F 148 8 negative
Copyright © 2011 SciRes. OJOTS
G. BACCHI ET AL.
16
cardiac allograft and 11 hours ± 4 hours for the kidney
allograft. The clinical results and outcomes are summa-
rized in Table 3.
Heart function recovered rapidly after transplant in
five patients who only needed low doses of inotropic
drugs. Two patients (no.3 and no. 6), presented with de-
layed recovery of heart function which required in-
creased inotropic support and (no. 6) intra-aortic balloon
pump assistance (IABP). Nevertheless, in both cases the
kidney was successfully transplanted with a 10 hour de-
lay in patient no.3 and immediately after the implant of
the IABP in patient no 6. Diuresis was immediate in four
patients and delayed in the other three (no.1, no.3 and no.
7) who required haemodialysis for 16, 3 and 4 days, re-
spectively.
The duration of postoperative hospitalization ranged
from 25 days to 58 days and at discharge time, both
grafts in all patients were well-functioning (mean left
ventricular ejection fraction 60% ± 6.2%; mean serum
creatinine 1.4 mg/dL ± 0.3 mg/dL). During the follow-up
period, one patient (no. 2) was free of adverse events,
while five patients presented with hypertension which is
being treated with anti-hypertensive drugs. Insulinde-
pendent diabetes mellitus developed in patient no. 1 and
patient no. 4, while patient no. 7 experienced a urinary
tract infection. Chronic obstructive pulmonary disease
was noted in patient. no. 1.
As regards organ rejection, 3 patients experienced car-
diac allograft rejection (43%) and 2 patients experienced
kidney rejection (28%). There were a total of seven car-
diac allograft rejection episodes, clinically significant in
three patients (grade 3A, ISHLT ) and of these three pa-
tients, two also experienced a kidney rejection episode.
In the two patients that experienced both kidney and
heart rejection, these episodes were independent of each
other.
After a mean follow-up period of 44.8 months ± 24.4
months, all the patients are still alive.
Six of the cardiac allografts still have normal systolic
function and are New York Heart Association (NYHA)
class I or II. The worst current cardiac function (EF 42%)
is that of patient no. 1, who is also the oldest of the pa-
tients and has the longest graft surv ival time in our series,
with 75 months of follow-up. Unfortunately, 58 months
after HTX he developed emphysema and is now NYHA
class III.
All of the kidney allografts continue to function satis-
factorily with a mean serum creatinine of 1.2 mg/dL ±
0.2 mg/dL in six patients, while in pt no. 7, an increase in
serum creatinine concentration (2.9 mg/dL) has been
noted.
In fact, patient no. 7 already had impaired renal func-
tion at the second month following r ecurring episodes of
sepsis (Escherichia coli) originating from his native
polycystic kidney. Three months after HKT, he under-
went left nephrectomy, it was not possible to perform the
operation before this time due to the severely compro-
mised cardiac status of the patient. Biopsy was per-
formed 6 months after HKT and revealed signs of renal
tubulophathy. No functional improvement was noticed
after the reduction of the calcine urin inhibitors.
4. Discussion
Several studies regarding combined heart-kidney trans-
plantation supports this option as a promising opportu-
nity for patients with the co-existing failure of both
organs.
Although one of the first multi-institutional studies [3]
of 82 HKT reported a survival rate 2-year lower than
Table 3. Patient outcome data.
Graft function at discharge timeCurrent graf t function
Pt.no. ICU stay
days
Hospital
dis-
charge
days
LVEF
%
CI
L/min/m2
Cre
mg/dL
Heart
rejection
no.
Kidney
rejection
no.
Adverse
event LVEF
%
CI
L/min/m2
Cre
mg/dL
Survival Follow-up
months
1 17 42 55 4.57 1.1 none noneHTN IDD
COPD 42 3.78 1.2 alive 75
2 4 36 50 3.02 1.1 none nonenone 63 2.89 1.0 alive 67
3 16 58 65 4.30 1.7 none noneHTN 70 2.79 1.5 alive 65
4 8 26 58 3.79 1.8 none none IDD 63 3.38 2.0 alive 39
5 7 25 67 3.12 1.3 2 noneHTN 65 3.45 1.3 alive 35
6 6 42 65 3.30 1.1 4 1 HTN 77 2.46 1.7 alive 21
7 6 39 60 3.50 1.8 1 1 HTN UTI67 5.10 2.9 alive 12
CI, cardiac i ndex; COPD, chronic obs tructive pul monary disease; Cr e, serum creati nine; HTN, h ypertension; ICU, intensiv e care unit; IDD, insulin-dependent
diabetes; LVEF left ventricular ejection fraction; UTI, urinary tract infection.
Copyright © 2011 SciRes. OJOTS
17
G. BACCHI ET AL.
that of isolated heart transplant recipients, according to
the UNOS database, this difference was not statistically
significant; several more recent studies from single
centres with a low number of cases have yielded en-
couraging results, both in terms of long-term graft
function and patient survival [4-7].
Moreover, in a recent analysis Russo et al [8], refer-
ring also to the UNOS database, found that low risk
patients with an estimated filtration rate of less than 33
mL/min gained a survival benefit from HKT over heart
transplantation alone.
In our experience with 7 patients who have under-
gone HKT with single donor allografts all patient are
alive at a mean follow-up of 45 months ± 24 months
(range, 75 months - 12 months) which supports the sat-
isfactory results of this procedure.
Some advantages can be noted in using the same do-
nor and a single operative session for both organs.
Firstly the recipients have a single exposure to alloan-
tigen avoiding further antigenic stimulation. Secondly,
they have a single induction immunosuppressive treat-
ment and, thirdly, when the surgical procedure is car-
ried out in the same surgical session they avoid a sub-
sequent anaesthesia and also the cold renal storage is
reduced. Some authors [6,9] have stated a preference
for a staged approach involving a later second operative
procedure. However, in the experience of kidney trans-
plantation, prolonged cold ischemic time (CIT) is a
well-known risk factor for delayed graft function [10]
which is itself associated to lower graft function and
graft survival rate in the long term [11].
In our experience, except for one staged procedure
which was necessary due to instable hemodynamic
conditions, all kidneys were immediately implanted
after the closure of the chest allowing for a CIT of no
longer than 10 hours.
Of note, many studies describe a low rate of rejection
in HKT [3,6,9] which is in accordance with another
recent analysis from UNOS clinical data [12] that
showed that both kidney and heart allograft rejections
are reduced when compared with each respective al-
lograft alone (17% vs 24%, p < 0.001 and 26% vs 52%,
p < 0.001; respectively). More generally they found that
the heart liver and kidney allografts are themselves
protected from rejection and that they protect the other
organ when transplanted from the same donor. It ap-
pears that any organ transplant combination may induce
tolerance or reduce host immunor esponsiveness, but the
mechanisms of this immune event in human patients are
not clearly understood even if various hypotheses have
been suggested [3,13,14].
In our study population, four out of seven patients
had no acute rejection episode of either organ and no
simultaneous rejection was noted. Despite the limited
data we have, this supports the fact that simultaneous
rejection is rare in HKT [15] thus suggesting that sur-
veillance of both organs is advisable and could be car-
ried out separately for each transplanted organ.
Despite the good clinical HKT results, the use for
two organs for one patient of such a scarcity of donors
may represent an ethical dilemma. We believe that this
issue can be at least partially settled with an optimal
candidate selection that is guided by the indications for
heart transplantation, viewing the combined kidney
transplant as a possibility to remove a contraindication
to heart transplant alone. Of note, as opposed to
end-stage kidney disease that can be artificially treated
with long-term dialysis, no mechanical device is cur-
rently represent a valuable option as a substitute for
heart transplantation for resolving end stage heart fail-
ure. Thus, heart transplantation may be the only life-
saving option in patients with end stage heart failure
that additionally suffer from end-stage kidney disease.
On the other hand, we do not believe that HKT should
be an option permitting kidney transplant in patients
with end-stage kidney disease and severe but non-
symptomatic heart disease, because heart transplant is
not proven to improve survival in these patients as
compared with optimal medical treatment for heart
failure [16]. Our current policy is to consider HKT in
patients with an indication for heart transplant, a low
comorbidity profile, and a creatinine clearance of less
than 30 mL/min due to parenchyma kidney disease [17],
(i.e. excluding patients with renal insufficiency secon-
dary to lo w-c ard iac ou tpu t alon e).
In conclusion, our results support the previously re-
ported data about HKT, suggesting that this procedure
has become a valuable option for selected patients
needing a heart transplant with concurrent severe renal
failure. Donor scarcity underlines the need for a careful
and stringent selection of candidate patients in order to
optimize the best outcome for both organs.
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