Combined Heart-kidney Transplantation: A Single Center Experience

doi:10.4236/ojots.2011.12003

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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)

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: [email protected]

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,

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

G. BACCHI ET AL.

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

L/min/m2

Cre

mg/dL

Heart

rejection

no.

Kidney

rejection

no.

Adverse

event LVEF

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.

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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