2356 M.E. Baccaro et al.

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tients undergoing lung transplantation for emphysema. Arch Bronco-
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suscitation on delayed graft function: results of a monocentric anal-
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Received for publication: 28.10.09; Accepted in revised form: 21.1.10

Nephrol Dial Transplant (2010) 25: 23562363

doi: 10.1093/ndt/gfq024
Advance Access publication 4 February 2010

Combined liverkidney transplantation in patients with cirrhosis and

chronic kidney disease

M.E. Baccaro1,*, M.N. Ppin1,*, M. Guevara1, J. Colmenero1, J.V. Torregrosa2, M. Martn-Llah1,

E. Sol1, N. Esforzado2, J. Fuster3, J.M. Campistol2, V. Arroyo1, M. Navasa1, J. Garca-Valdecasas3 and
P. Gins1
1
Liver Unit, 2Nephrology and Renal Transplant Department and 3Department of Surgery, Hospital Clnic, University of Barcelona,
Institut d'Investigacions Biomdiques August Pi-Sunyer (IDIBAPS), Centro de Investigacin Biomdica en Red de Enfermedades
Hepticas y Digestivas (CIBEREHD), Barcelona, Catalunya, Spain
Correspondence and offprint requests to: Mnica Guevara. E-mail: mguevara@clinic.ub.es
*
These authors have contributed equally to this work

Abstract plantation. Patients with CLKT had a higher incidence of

The outcome of patients with cirrhosis and chronic kid-
ney disease treated with combined liverkidney trans-
plantation (CLKT) is not well known because most
series of patients treated with CLKT include not only
patients with cirrhosis but also patients with inherited
diseases without cirrhosis. To evaluate to what extent
the combined kidney transplantation impairs posttrans-
plantation outcome compared to liver transplantation
(LT) alone, the outcome of patients with cirrhosis and
chronic kidney disease treated with CLKT (n = 20)
was compared to that of a group of patients with cirrho-
sis without chronic kidney disease treated with LT alone
matched by age, sex, year of transplantation and severity
of cirrhosis (n = 60). The primary end point of the study
was survival, and secondary end points were outcome of re-
nal function and complications within 6 months of trans-
bacterial infections and transfusion requirements com-
pared to LT patients. The incidence of acute renal failure
during the first 6 months was similar, yet the severity of
renal failure was greater in patients with CLKT. Hospital
and intensive care unit (ICU) stays were longer in the
CLKT group. One- and three-year survival probabilities
in patients treated with CLKT were 80 and 75% compared
to 97 and 88%, respectively, in patients treated with LT. In
conclusion, CLKT for patients with cirrhosis and chronic
kidney disease is associated with a relatively high frequen-
cy of postoperative complications that moderately impairs
short-term survival. However, 3-year survival of patients
with cirrhosis treated with CLKT is excellent.
Keywords: cirrhosis; liver transplantation; renal transplantation

The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org
CLKT in patients with cirrhosis and chronic kidney disease
Introduction
Combined liverkidney transplantation (CLKT) is per-
formed frequently in patients with cirrhosis with associat-
ed kidney diseases. Most of these patients have chronic
renal failure due to parenchymal renal diseases, in most
cases glomerulopathy associated with alcoholic cirrhosis
or with chronic hepatitis B or C infection, or chronic renal
failure due to kidney rejection after kidney transplantation
[110]. CLKT has also been used for patients with cirrho-
sis and hepatorenal syndrome (HRS), although the use of
renal transplantation in this setting is controversial due to
the potential reversibility of renal failure after liver trans-
plantation (LT) alone [1113].
Since the introduction of the Model for End-stage Liver
Disease (MELD) score system in the USA and other
countries, the number of patients treated with CLKT has in-
creased markedly, mainly due to the fact that the presence of
renal failure associated with liver disease raises the MELD
score and thus increases the likelihood of transplantation
[14,15]. Despite the relatively common use of CLKT in cir-
rhosis, a number of issues remain poorly understood.
Among others, it is not known to what extent the associated
renal transplantation affects posttransplantation outcomes
in patients with cirrhosis. The existing limited information
is due, at least in part, to the fact that most published series
of patients treated with CLKT include not only patients
with cirrhosis but also a significant number of patients with
metabolic diseases, such as primary hyperoxaluria, or poly-
cystic kidney and liver disease [1,2,4,5,8,9,1629]. On this
background, the aim of the current study was to assess the
survival and postoperative complications of patients with
cirrhosis and chronic kidney diseases [30] treated with
CLKT in a single institution. To evaluate to what extent
the combined kidney transplantation affects posttransplan-
tation outcome compared to LT alone, the outcome of pa-
tients with CLKT was compared to that of a group of
patients with cirrhosis treated with LT alone matched by
age, sex, year of transplantation and severity of cirrhosis.
Materials and methods
Study population
Data from all patients with CLKT performed in the Hospital Clnic (Bar-
celona, Catalonia, Spain) between December 1994 and December 2004
were retrospectively reviewed. During this period, the criteria to perform
a CLKT in our unit were as follows: (i) in patients with previous kidney
transplant existence of chronic kidney disease either requiring haemo-
dialysis or with glomerular filtration rate (GFR) below 30 mL/min asso-
ciated with decompensated cirrhosis or compensated cirrhosis but with
portal hypertension and (ii) in patients without previous kidney transplant
decompensated cirrhosis with chronic kidney disease either requiring
haemodialysis or with a serum creatinine >1.5 mg/dL (this latter criterion
was later substituted by a GFR below 30 mL/min). These criteria are sim-
ilar to those that have been proposed in a recent consensus conference
[31]. Before transplantation, a renal biopsy was performed to make the
diagnosis of the renal disease, unless contraindicated because of severe
coagulopathy (prothrombin time <50% and platelet count <50 000 per
/L). No patient with HRS was treated with CLKT. Patients with liver
diseases other than cirrhosis and associated kidney diseases treated with
CLKT were excluded from the study.
A group of patients with cirrhosis treated with LT matched by age, year
of transplantation and severity of liver disease, as estimated by the Child
Pugh score, was also analysed. For each patient treated with CLKT, three
2357
matched patients treated with LT alone were analysed. The study was ap-
proved by the institutional review board of our centre and included a total of
20 patients treated with CLKT and 60 patients treated with LT alone.
Methods
Data collected from the patient's clinical records were incorporated into a
database that included demographic parameters, previous complications
of cirrhosis, biochemical parameters measured immediately before trans-
plantation, ChildPugh score at the time of transplantation, need for dial-
ysis previous to transplantation, comorbidities (such as diabetes mellitus
or hypertension), date of transplantation, ABO blood group (ABO) and
human leukocyte antigen (HLA) mismatches. Results of cross-matches
were also added to the database for analysis, even if they were not used
at the time of transplantation. Liver function tests, as well as complete
blood count and coagulation tests, were registered at baseline (pretrans-
plantation) and during hospitalisation. Renal function was recorded at
baseline, during hospitalisation and at 1, 3, 6, 12 and 36 months after
transplantation. MELD score at the time of transplantation was retrospec-
tively calculated for each patient using the standard formula (www.mayo-
clinic.org/meld/mayomodel6.html). International normalized ratio (INR)
was not available in patients transplanted before 1997. In these patients,
INR was calculated according to the following formula: (prothrombin
time of patient/control prothrombin time)ISI, ISI being the international
sensitivity index for thromboplastin [32].
Primary end points of the study were 1- and 3-year survival probabil-
ities. Secondary end points were development of complications during the
first 6 months after transplantation and outcome of renal function.
The complications analysed were as follows: intraabdominal bleeding,
infections, acute rejection, renal failure and side effects of immunosuppres-
sive drugs. Intraabdominal bleeding was assessed during surgery and with-
in the first week posttransplantation, while renal failure, infections, acute
rejection and side effects of immunosuppressive drugs were evaluated dur-
ing the first 6 months after transplantation. In addition, the time spent in the
ICU and the total duration of the hospitalisation were also analysed.
Surgical procedure and immunosuppression
Liver and kidney transplantations were performed by experienced sur-
geons according to standard techniques with preservation of vena cava
and without bypass except in three patients. For CLKT, the kidney was
inserted after the liver and placed extraperitoneally. Before transplanta-
tion, cross-matches were positive in 17% of the CLKT group and in
4% of the LT group (not statistically significant, ns). Immunosuppression
was based on calcineurin inhibitors in all patients. All transplanted pa-
tients before 2000 received cyclosporine (CsA), while among those trans-
planted after 2000, 56% received tacrolimus in the LT group compared to
15% in the CLKT group. Six patients (30%) from the CLKT group re-
ceived an induction therapy (three with thymoglobulin, two with mono-
clonal antibody muromonab-CD3 (OKT3) and one with monoclonal
antibodies directed against interleukine-2 receptor (anti-IL2)). Only four
of LT patients (7%) received an induction therapy (anti-IL2 antibodies).
Mycophenolate mophetil (MMF) was used more frequently in CLKT pa-
tients compared to LT patients (45 vs 17%, P = 0.01). MMF was uncom-
monly used in LT patients because most of these patients did not have
renal failure at the time of transplant. Acute liver or kidney rejection
was treated with a similar regimen of steroid pulses in both groups.
Definitions
Renal function. The presence of chronic kidney disease before transplan-
tation was defined by using the criteria of the National Kidney Foundation
[30].
Posttransplant renal function was classified according to the following
definitions:
(i) For CLKT patients, acute renal failure (ARF) was defined as an
increase of serum creatinine value >50% over the lowest value achieved
posttransplantation. In the case of primary dysfunction of the graft, a
worsening of renal function or an absence of change from pretransplant
serum creatinine value was also considered as ARF;
(ii) For LT patients, ARF was defined as an increase of serum creati-
nine >50% over the pretransplant value, with a final level >1.5 mg/dL;
(iii) For patients with pretransplant normal renal function, complete
resolution of ARF was defined as a reduction in serum creatinine to a
2358
value <1.5 mg/dL; for patients with pretransplant kidney disease, com-
plete resolution of ARF was defined when serum creatinine decreased
to a final value within 25% of the lowest posttransplant value;
(iv) Chronic kidney disease was defined using the criteria of the Na-
tional Kidney Foundation [30].
Other complications. Selection of donors was based on ABO compatibility,
organ size and quality of donor. HLA matching was disregarded. Liver and
kidney rejections were diagnosed on the basis of clinical findings and con-
firmed by a biopsy whenever possible. Liver graft survival was defined as
the days of survival with a functioning organ without the need for retrans-
plantation. Renal graft survival was calculated as time elapsed before reach-
ing chronic dialysis or end-stage renal disease as defined by Kidney
Disease Outcomes Quality Initiative Guidelines, from the National Kidney
Foundation (K/DOQI) stage V (www.kidney.org/professionals/kdoqi/
guidelines) or retransplantation. Infectious complications were defined
by the presence of systemic or local signs of infection together with positive
cultures and/or compatible radiological findings requiring intravenous ad-
ministration of antimicrobial agents. Significant hypotension was defined
as a systolic blood pressure <80 mm Hg or a mean arterial blood pressure of
<60 mm Hg. Shock was defined as hypotension associated with tissue hy-
poperfusion or the need of vasopressors to maintain vital organ functions.
Vascular complications were those associated with surgery-related bleeding
or any lesion of arteries or veins of the graft. Biliary complications were
those related to stenosis, leak or collection in the biliary tree. Renal com-
plications were any urological problem related to the transplanted kidney.
Complications related to the use of steroids/immunosuppressors were as
follows: hyperglycaemia, high blood pressure, osteopenia, myopathy, psy-
chosis, ARF associated with high levels of calcineurin inhibitors with or
without any other cause of renal failure, dyslipidaemia, hirsutism, gingival
hyperplasia, neurotoxicity, hyperuricaemia, cytopenias and severe diar-
rhoea [33]. Hepatitis C infection was treated with interferon and ribavirin
M.E. Baccaro et al.
before transplantation only in patients with ChildPugh A cirrhosis (six out
of the 60 patients treated with LT). Hepatitis C recurrence after transplan-
tation was treated with interferon and ribavirin in patients with severe re-
currence as indicated by clinical and histological criteria (17 of the 60 LT
patients and only one of the 20 CLKT patients). Hepatitis B infection was
treated with lamivudine before transplantation and a combination of lami-
vudine and antihepatitis B immunoglobulin after transplantation.
Statistics
Student's T-test or MannWhitney test was used to compare continuous
variables. Categorical variables were analysed using the Chi-square test or
Fisher test as appropriate. Probability of survival was calculated using the
KaplanMeier method, and curves were compared with the log rank test.
Results are presented as mean standard deviation unless otherwise spec-
ified. All reported P-values are two-tailed, and values of <0.05 were con-
sidered statistically significant, except for the univariate analysis of
survival where a P-values <0.1 was considered as significant. All statistical
analysis was performed using the SPSS 14.0 program for Windows (SPSS,
Chicago, IL).
Results
Baseline characteristics of the patients
Table 1 shows baseline characteristics of patients included
in the study at the time of transplantation. Causes of chron-
ic kidney disease in the 20 patients treated with CLKT
were chronic kidney rejection after renal transplantation

Table 1. Baseline characteristics of patients at the time of transplantationa

Combined liverkidney Liver transplantation

Variable transplantation (n = 20) (n = 60) P

Age (years) 46 8 (3060) 49 7 (2462) ns

Sex (M/F) 14/6 36/24 ns
Aetiology of cirrhosis
Hepatitis C infection 10 31
Alcohol 5 8
Alcohol + Hep C or B infection 1 6
Otherb 4 15
Stage of chronic kidney disease
Stages 3/4/5c 4/3/13
Renal support
Dialysis before transplantation 13
Median time in dialysis (months) 72
Previous major complications of cirrhosisd 16 43 ns
ChildPugh
Class (A/B/C) 8/11/1 24/33/3 ns
Score 7 1.5 (510) 7 1.5 (510) ns
MELD score 20 4 (1127) 11 3.3 (622) 0.000
Ascites at transplantation 6 12 ns
Bilirubin (mg/dL) 1.3 0.7 (0.33.1) 2.3 2.1 (0.412) ns
Albumin (g/L) 35 7 (2245) 35 6 (2147) ns
Prothrombin time (%) 76 15 (49100) 71 16 (35100) ns
Serum creatinine (mg/dL) 5.6 3.7 (1.615) 0.96 0.27 (0.62.1) 0.000
MDRD (mL/min/1.73 m2)e 18 14 (454) 87 27 (27153) 0.000
Serum sodium (mEq/L) 132 3.6 (132146) 137 4.5 (118146) 0.051
Hematocrit (%) 31 5 (2543) 35 6 (2147) 0.006

a
Values are mean SD or number of patients. Values in brackets are ranges.
b
In patients treated with combined liverkidney transplantation: hepatitis B infection plus hepatitis C infection in two patients, hepatitis B infection and
cryptogenic in one patient each; in patients treated with liver transplantation alone: primary biliary cirrhosis in five patients, hepatitis B in three,
cryptogenic and Wilson's disease in two and hepatitis C and B infection, autoimmune hepatitis and haemochromatosis in one patient each.
c
Stage 3: glomerular filtration rate 3059 mL/min; stage 4: glomerular filtration rate 1529 mL/min; stage 5: glomerular filtration rate <15 mL/min or
dialysis [30].
d
Either ascites, gastrointestinal bleeding, hepatic encephalopathy or bacterial infection.
e
MDRD, glomerular filtration rate estimated using Modification of Diet in Renal Disease equation [34].
CLKT in patients with cirrhosis and chronic kidney disease
in 12 patients (in 10 patients confirmed by kidney biopsy),
glomerulonephritis in six (IgA glomerulonephritis in four
and membranous nephropathy and focal segmental glo-
merulosclerosis in one patient each, all confirmed by kid-
ney biopsy) and unknown in two patients. While all
patients in the CLKT group had chronic kidney disease
stages 35, only three (5%) of patients in the LT had im-
pairment of renal function at the time of transplantation.
Causes of renal failure in these patients were diuretic ther-
apy, type 1 HRS and acute tubular necrosis in one patient
each. Mean pretransplant serum creatinine values in these
three patients were 1.73 0.3 mg/dL.
Renal failure after transplantation
After transplantation, ARF occurred in 11 (55%) patients
in the CLKT group during hospitalisation and in 13 (65%)
patients during the first 6 months of follow-up (Table 2). In
the LT group, the incidence of ARF was 35% during hos-
pitalisation and 70% during the first 6 months of follow-up
(P = ns vs CLKT). Five patients (25%) needed renal re-
placement therapy within the first 6 months after trans-
plant compared to only two patients treated with LT
(3.3%) (P = 0.009).
Despite the similar incidence of ARF in both groups, the
causes were markedly different (Table 2). In the CLKT
group, 20 episodes of ARF occurred, 50% being due to
acute tubular necrosis (six episodes) or rejection (four epi-
sodes). By contrast, in the LT group, 67% of the 62 epi-
sodes of ARF were attributed to toxicity by calcineurin
inhibitors as suggested by increased serum levels of the
drugs and lack of other causes of renal failure. The out-
come of renal function at 6 months was similar between
both groups. Mean serum creatinine at 6 months after
Table 2. Characteristics of posttransplant renal failure in patients treated with combined liverkidney transplantation and patients treated with liver
transplantationa
Combined liverkidney
transplantation (n = 20)
Acute renal failure
Hospitalisation 11 (55%)
During first 6 months 13 (65%)
Number of episodes 20
Causes
CsA/FK 3 (15%)
ATN 6 (30%)
Rejection 4 (20%)
Sepsis 3 (15%)
Otherb 4 (20%)
Peak of serum creatinine (mg/dL) during 3.9 1.7 (1.97.4)
the first episode of ARF
Dialysis posttransplantation 5 (25%)
Chronic kidney disease
Incidence 5 (25%)
Serum creatinine at 6 months (mg/dL) 2.47 0.9 (1.53.3)
MDRD (mL/min/1.73 m2) 35 17 (2254)
CsA, cyclosporine; FK, tacrolimus; ATN, acute tubular necrosis.
a
Values are number of patients and percentages (in brackets) or mean SD.
b
CLKT group: prerenal and obstructive (one patient each), unknown cause (two patients). LT group: multifactorial (six patients), unknown cause (five
patients), prerenal (three patients), nephrotoxicity (one patient).
2359
transplantation was 1.48 0.7 mg/dL in CLKT group
and 1.40 0.4 mg/dL in LT patients (P = ns) (Figure 1).
The prevalence of chronic kidney disease in the CLKT
group 6 months after transplantation was 25% compared
to 13% in the LT group (P = ns).
Complications after transplantation
Table 3 shows the complications observed within the first
6 months after transplantation in the two study groups. In-
fectious complications were significantly more frequent in
CLKT patients than in LT patients during hospitalisation.
At 6 months after transplantation, the incidence of infec-
tion was no longer significantly different between the two
groups. Shock was more frequent in CLKT patients than in
LT patients due to a higher frequency of septic shock that
occurred in 15% of patients receiving CLKT versus none
of the patients in the LT group. Blood transfusion require-
ments were greater in patients treated with CLKT patients
compared to the LT group. This was mainly due to higher
transfusion requirements during the surgical procedure (a
median of 5 units for CLKT vs 4 units for LT, P = 0.031).
Complications associated with immunosuppressive ther-
apy were common in both groups of patients. Hypergly-
caemia or impairment of previous diabetes mellitus
occurred in 81 and 77% of patients, respectively. De novo
hypertension occurred in 67% of patients in the LT group
vs 45% of patients receiving a CLKT (P = ns). ARF asso-
ciated with high plasma levels of calcineurin inhibitors oc-
curred in 48% of patients in the LT group vs 5% of
patients in the CLKT group (P < 0.001). Dyslipidaemia,
neurotoxicity and transient hypomagnesaemia occurred
in <15% of patients.
Liver transplantation
(n = 60) P
21 (35%) ns
42 (70%) ns
62 ns
42 (67%)
1 (2%)
4 (7%)
15 (24%)
2 0.5 (1.63.8) 0.002
2 (3.3%) 0.009
8 (13%) ns
1.8 0.24 (1.62.2) ns
41 6 (3448) ns
2360 M.E. Baccaro et al.

Fig. 1. Serum creatinine values (mean standard deviation) in patients treated with combined liverkidney transplantation (continuous line) and
patients treated with liver transplantation alone (discontinuous line). *P < 0.001, **P < 0.01.

Acute liver rejection rate was similar in CLKT and LT
recipients (seven patients 35% and 27 patients 45%
at 6 months, respectively, P = ns). Only four patients (20%)
receiving CLKT suffered kidney rejection. Kidney rejec-
tion occurred in two of the three patients with positive
cross-match and in only two of the 17 patients with nega-
tive cross-match (P = 0.08). All episodes of liver or kidney
rejection responded to treatment, in no case leading to
graft failure. Liver and kidney rejection occurred simulta-
neously in only three patients.
The modification of the immunosuppressive protocols
after the year 2000 was associated with a slightly higher
frequency of liver rejection (P = 0.04) but not kidney re-
jection in patients treated with CLKT. No significant
changes were observed in the frequency of liver rejection
in patients treated with LT.
Overall surgical reinterventions were more frequent in
the CLKT group (45 vs 18%, P = 0.034). The higher rate
of reinterventions in the CLKT group was due to urolog-
ical complications associated with the transplanted kidney,

Table 3. Complications of patients treated with combined liverkidney transplantation and liver transplantationa

Combined liverkidney Liver transplantation

Complication transplantation (n = 20) (n = 60) P

Medical
Infections
During hospitalisation 11 (55%) 13 (22%) 0.01
During first 6 months after transplant 11 (55%) 20 (33%) ns
Shock 6 (30%) 3 (5%) 0.006
Transfusion requirements b
Intraoperative 5 (211) 4 (027) 0.031
First week after transplantation 2 (036) 1 (016) ns
Total 9 (245) 7 (042) 0.009
Liver rejection at 6 monthsc 7 (35%) 27 (45%) ns
Renal rejection at 6 months 4 (20%)
Surgical
Type of complication
Vascular 4 (20%) 20 (33%) ns
Biliary 8 (40%) 16 (27%) ns
Urology 10 (50%)
Need for reintervention
Total (liver and kidney) 9 (45%) 11 (18%) 0.034
Liver 6 (30%) 11 (18%) ns

a
Values are number of patients and percentages (in brackets) or means SD.
b
Units of packed red blood cells are expressed as median values. Values in brackets are ranges.
c
Eight episodes of rejection (seven confirmed by liver biopsy) in patients treated with combined liverkidney transplantation and 30 episodes of re-
jection (25 confirmed by liver biopsy) in patients treated with liver transplantation alone.
CLKT in patients with cirrhosis and chronic kidney disease
which developed in half of patients receiving a CLKT.
Main causes of urological reintervention were bleeding
and ureteral stenosis. Vascular and biliary complications
occurred at a similar rate in both groups during follow-up.
Patients receiving CLKT had a longer stay in ICU and
total longer in-hospital stay than patients receiving LT (me-
dian time, 7 vs 5 days and 29 vs 21 days, respectively, P =
0.037 and P = 0.01).
The frequency of complications after transplantation
was similar between patients with stages 34 of chronic
kidney disease and those with stage 5. When patients
transplanted during the second half of the study period
were compared to those transplanted within the first half,
significant differences were observed only in the need for
transfusion requirements but not in the frequency of other
postoperative complications.
Graft survival
There was no primary graft failure (liver or kidney grafts)
in either group. Actuarial liver graft survival was 80 and
95% for CLKT and LT, respectively, at 1 year (P =
0.038) and 75 and 87%, respectively, at 3 years (P = ns).
One patient from the LT group required retransplantation
for cirrhosis due to recurrent hepatitis C infection 2 years
after transplantation. Development of cirrhosis due to re-
current hepatitis C infection occurred in one patient from
the CLKT group and nine from the LT group (P = 0.4).
No CLKT patients reached dialysis at 3 years. No
CLKT patients required kidney retransplantation during
the 3-year follow-up.
Survival
Patients treated with CLKT had a 1-year survival that was
slightly lower than that of patients treated with LT (80 vs
97%, respectively, P = 0.014). The probability of survival
at 3 years was also lower in the CLKT group, yet the dif-
ference between the two groups did not reach statistical
significance (75 and 88%, respectively, P = ns) (Figure 2).
Fig. 2. Probability of survival of patients treated with combined liver
kidney transplantation (continuous line) and patients treated with liver
transplantation alone (discontinuous line); values under the graph are
patients at risk.
2361
Causes of death in patients with CLKT were infectious
complications in two patients and cerebrovascular accident
and respiratory failure in one patient each. Causes of death
in patients with LT were infectious complications in two
patients and hepatocellular carcinoma, laryngeal carcino-
ma, multiorgan failure after retransplantation, amyotrophic
lateral sclerosis and acute pancreatitis in one patient each.
Factors associated with an increased risk of death at 1 year
in patients treated with CLKT were serum bilirubin and
MELD score before transplantation and development of
shock, infections and ARF during hospitalisation. Both
short- and long-term survival of patients with stage 5 chronic
kidney disease were similar to those of patients with stages
34 (P = ns). The modification of the immunosuppressive
protocols during the study period did not have a significant
impact on patient survival. Likewise, there were no signifi-
cant differences in the survival of patients transplanted with-
in the first part of the study period and that of patients
transplanted within the second part of the study period.
Discussion
The main findings of the current study are that CLKT in pa-
tients with cirrhosis and associated chronic kidney disease
can be performed with an acceptable rate of postoperative
complications and a relatively high survival considering that
these patients have a combination of severe chronic kidney
and liver disease before transplantation and are submitted to
two solid organ transplants. In fact, in the current study, the
frequency of postoperative complications was only moder-
ately higher and 1-year survival moderately lower than those
observed in a contemporary group of patients with cirrhosis
of similar severity but without chronic kidney disease sub-
mitted to LT alone. Three-year survival, although slightly
lower in the group of patients treated with CLKT, was not
significantly different among the two groups.
There are important issues about the design of this study
that deserve discussion. First, the validity of the conclu-
sions is limited by the fact that this is a retrospective study.
Nevertheless, it should be pointed out that the most impor-
tant variables analysed were collected prospectively in our
transplant database. On the other hand, it would be very
difficult to perform a prospective study of patients treated
with CLKT because of the low number of patients submit-
ted to this procedure annually. Second, when designing
this study, it was considered important to compare the out-
come of patients treated with CLKT to that of another
group of transplanted patients in order to assess the signif-
icance of the findings. The use of the whole population of
patients submitted to LT during the same period was not
considered appropriate because the possible differences
in outcome could be secondary to differences in the sever-
ity of cirrhosis at the time of transplantation between pa-
tients treated with CLKT and those treated with LT alone.
A comparative group of patients with chronic kidney dis-
ease submitted to LT alone was not feasible because all pa-
tients with cirrhosis and advanced chronic kidney disease
are considered candidates for CLKT. Therefore, it was felt
that a possible comparative group would be that of a con-
temporary series of patients submitted to LT alone but
2362
matched for the severity of cirrhosis. This group is also not
ideal because patients do not have chronic kidney disease
and are submitted to only one solid organ transplantation
and there might be some differences that are difficult to
account for between this group and that of patients treated
with CLKT, such as the aetiology of cirrhosis or the differ-
ent immunosuppressive protocols. Nevertheless, this last
approach was considered better than the other two ap-
proaches and could allow for some orientative assessment
of the outcome in patients treated with CLKT.
Patients receiving a CLKT had a high frequency of in-
fections and intraoperative bleeding and long ICU and hos-
pital stays. This increased frequency of complications was
probably responsible for the lower 1-year survival of pa-
tients treated with CLKT compared to that of patients trea-
ted with LT (80 vs 97%, respectively). The increased rate
of infections in patients with CLKT deserves a specific
comment because infections were associated with 1-year
mortality in the multivariate analysis. Our results are in
keeping with those of previous studies suggesting a major
role for sepsis on early posttransplantation mortality in pa-
tients treated with CLKT [7,9,25,29]. Moreover, infections
are a more common cause of death in recipients of CLKT
compared to recipients of kidney transplant alone [8]. Sev-
eral mechanisms may be accounted for by this increased
frequency of severe infections in patients treated with
CLKT, including more aggressive immunosuppressive re-
gimens (i.e. induction therapy, addition of MMF), pre-
transplant immunosuppresion in some patients due to
previous kidney grafts, presence of associated severe renal
failure and greater surgical manipulation compared to LT
alone. Whichever the mechanism responsible for the in-
creased frequency of severe infections is, patients submit-
ted to CLKT should be carefully evaluated for the presence
of infections and antibiotic therapy should be instituted
early when there is any suspicion of infection. Patients
treated with CLKT also had a relatively high incidence
of surgical complications, particularly bleeding and need
for reintervention. This has been reported in previous stud-
ies and is probably related to the increased surgical manip-
ulation required for CLKT with respect to LT alone [7,9].
Patients from both CLKT and LT groups had a high and
similar incidence of ARF during the 6-month period after
transplantation (65 vs 70%, respectively), yet peak serum
creatinine concentration and need for dialysis were higher
in patients from the CLKT group compared to those in the
LT group, indicating a greater severity of renal failure in
the CLKT group. This is also supported by the fact that
ARF was an independent risk factor of early mortality in
CLKT patients. Causes of ARF were markedly different
among groups. A high percentage (69%) of ARF in the
LT group was attributed to calcineurin inhibitors, whereas
most episodes of ARF in patients treated with CLKT were
due either to acute tubular necrosis or rejection. Neverthe-
less, as shown by the very similar serum creatinine levels
at 6 months, the causes of ARF had little impact on the
subsequent recovery of renal function.
Survival of patients with cirrhosis and chronic kidney
disease treated with CLKT was very good and only slightly
lower than that of patients with cirrhosis of similar severity
treated with LT alone (Figure 2). It should be noted, how-
M.E. Baccaro et al.
ever, that not all patients treated with CLKT had very ad-
vanced kidney disease, as few patients had stage 3 kidney
disease. This survival was similar to that reported in previ-
ous studies of patients treated with CLKT that included not
only patients with cirrhosis but also patients with metabol-
ic liver diseases without liver failure or polycystic liver and
kidney disease [2,4,5,9,12,16,17,19,2224,2628]. It is in-
teresting to note that baseline MELD score was an inde-
pendent predictive factor of posttransplant survival in the
CLKT group. Graft survival was excellent and comparable
to other studies. Liver rejection, as well as the kidney re-
jection rate, was similar to those reported in other studies
[5,7,8,12,16,17,22,24,25,28].
There is a final aspect of the current investigation that
needs to be discussed. The current series of patients treated
with CLKT does not include patients with HRS. Treatment
of patients with cirrhosis and HRS with CLKT instead of LT
alone is controversial because it increases the number of
kidneys used in patients with cirrhosis and may increase
the cost of therapy and be associated with higher morbidity
and mortality after transplantation [12,15]. The reason for
the lack of patients with HRS treated with CLKT in the cur-
rent series is that in our centre, patients with HRS are treated
before transplantation with the combination of terlipressin,
a vasopressin analogue, and albumin [35,36]. This strategy
has the advantage over CLKT of improving renal function
before transplantation, which may be associated with an im-
proved outcome after transplantation [37]. Moreover, this
approach does not increase the number of kidneys required
for treatment of patients with cirrhosis and renal failure.
In conclusion, the results of this study show that patients
with cirrhosis and chronic kidney disease can be submitted
to CLKT with an acceptable rate of postoperative compli-
cations and have a high survival rate. Therefore, CLKT is
an excellent approach to management of patients with cir-
rhosis and chronic kidney disease.
Acknowledgements. Thanks to Marco Pavesi for statistical support.
Grant funding from Fondo de Investigacin Sanitaria; EC07/90077 and
PI080126. M.E. Baccaro was supported by a grant from (FRIAT) Instituto
Reina Sofia de Investigacin Nefrologica. M.N. Ppin was supported by a
grant from Fondation du Centre Hospitalier de l'Universit de Montral.
M. Martin Llahi and Elsa Sola received support from FBBVA (Fundacin
Banco Bilbao Vizcaya Argentaria) Centro de Investigacin Biomedica en
Red Enfermedades Hepaticas y Digestivas (CIBERehd) is funded by the
Instituto de Salud Carlos III.
Conflict of interest statement. None declared.
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Received for publication: 2.4.09; Accepted in revised form: 12.1.10