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

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 2357

Introduction 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.
Combined liverkidney transplantation (CLKT) is per-
formed frequently in patients with cirrhosis with associat-
Methods
ed kidney diseases. Most of these patients have chronic
Data collected from the patient's clinical records were incorporated into a
renal failure due to parenchymal renal diseases, in most database that included demographic parameters, previous complications
cases glomerulopathy associated with alcoholic cirrhosis of cirrhosis, biochemical parameters measured immediately before trans-
or with chronic hepatitis B or C infection, or chronic renal plantation, ChildPugh score at the time of transplantation, need for dial-
failure due to kidney rejection after kidney transplantation ysis previous to transplantation, comorbidities (such as diabetes mellitus
or hypertension), date of transplantation, ABO blood group (ABO) and
[110]. CLKT has also been used for patients with cirrho-
human leukocyte antigen (HLA) mismatches. Results of cross-matches
sis and hepatorenal syndrome (HRS), although the use of were also added to the database for analysis, even if they were not used
renal transplantation in this setting is controversial due to at the time of transplantation. Liver function tests, as well as complete
the potential reversibility of renal failure after liver trans- blood count and coagulation tests, were registered at baseline (pretrans-
plantation (LT) alone [1113]. plantation) and during hospitalisation. Renal function was recorded at
baseline, during hospitalisation and at 1, 3, 6, 12 and 36 months after
Since the introduction of the Model for End-stage Liver transplantation. MELD score at the time of transplantation was retrospec-
Disease (MELD) score system in the USA and other tively calculated for each patient using the standard formula (www.mayo-
countries, the number of patients treated with CLKT has in- clinic.org/meld/mayomodel6.html). International normalized ratio (INR)
creased markedly, mainly due to the fact that the presence of was not available in patients transplanted before 1997. In these patients,
renal failure associated with liver disease raises the MELD INR was calculated according to the following formula: (prothrombin
time of patient/control prothrombin time)ISI, ISI being the international
score and thus increases the likelihood of transplantation sensitivity index for thromboplastin [32].
[14,15]. Despite the relatively common use of CLKT in cir- Primary end points of the study were 1- and 3-year survival probabil-
rhosis, a number of issues remain poorly understood. ities. Secondary end points were development of complications during the
Among others, it is not known to what extent the associated first 6 months after transplantation and outcome of renal function.
The complications analysed were as follows: intraabdominal bleeding,
renal transplantation affects posttransplantation outcomes infections, acute rejection, renal failure and side effects of immunosuppres-
in patients with cirrhosis. The existing limited information sive drugs. Intraabdominal bleeding was assessed during surgery and with-
is due, at least in part, to the fact that most published series in the first week posttransplantation, while renal failure, infections, acute
of patients treated with CLKT include not only patients rejection and side effects of immunosuppressive drugs were evaluated dur-
with cirrhosis but also a significant number of patients with 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.
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 Surgical procedure and immunosuppression
survival and postoperative complications of patients with Liver and kidney transplantations were performed by experienced sur-
geons according to standard techniques with preservation of vena cava
cirrhosis and chronic kidney diseases [30] treated with and without bypass except in three patients. For CLKT, the kidney was
CLKT in a single institution. To evaluate to what extent inserted after the liver and placed extraperitoneally. Before transplanta-
the combined kidney transplantation affects posttransplan- tion, cross-matches were positive in 17% of the CLKT group and in
tation outcome compared to LT alone, the outcome of pa- 4% of the LT group (not statistically significant, ns). Immunosuppression
tients with CLKT was compared to that of a group of was based on calcineurin inhibitors in all patients. All transplanted pa-
tients before 2000 received cyclosporine (CsA), while among those trans-
patients with cirrhosis treated with LT alone matched by planted after 2000, 56% received tacrolimus in the LT group compared to
age, sex, year of transplantation and severity of cirrhosis. 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
Materials and methods antibodies directed against interleukine-2 receptor (anti-IL2)). Only four
of LT patients (7%) received an induction therapy (anti-IL2 antibodies).
Study population Mycophenolate mophetil (MMF) was used more frequently in CLKT pa-
Data from all patients with CLKT performed in the Hospital Clnic (Bar- tients compared to LT patients (45 vs 17%, P = 0.01). MMF was uncom-
celona, Catalonia, Spain) between December 1994 and December 2004 monly used in LT patients because most of these patients did not have
were retrospectively reviewed. During this period, the criteria to perform renal failure at the time of transplant. Acute liver or kidney rejection
a CLKT in our unit were as follows: (i) in patients with previous kidney was treated with a similar regimen of steroid pulses in both groups.
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 Definitions
portal hypertension and (ii) in patients without previous kidney transplant Renal function. The presence of chronic kidney disease before transplan-
decompensated cirrhosis with chronic kidney disease either requiring tation was defined by using the criteria of the National Kidney Foundation
haemodialysis or with a serum creatinine >1.5 mg/dL (this latter criterion [30].
was later substituted by a GFR below 30 mL/min). These criteria are sim- Posttransplant renal function was classified according to the following
ilar to those that have been proposed in a recent consensus conference definitions:
[31]. Before transplantation, a renal biopsy was performed to make the (i) For CLKT patients, acute renal failure (ARF) was defined as an
diagnosis of the renal disease, unless contraindicated because of severe increase of serum creatinine value >50% over the lowest value achieved
coagulopathy (prothrombin time <50% and platelet count <50 000 per posttransplantation. In the case of primary dysfunction of the graft, a
/L). No patient with HRS was treated with CLKT. Patients with liver worsening of renal function or an absence of change from pretransplant
diseases other than cirrhosis and associated kidney diseases treated with serum creatinine value was also considered as ARF;
CLKT were excluded from the study. (ii) For LT patients, ARF was defined as an increase of serum creati-
A group of patients with cirrhosis treated with LT matched by age, year nine >50% over the pretransplant value, with a final level >1.5 mg/dL;
of transplantation and severity of liver disease, as estimated by the Child (iii) For patients with pretransplant normal renal function, complete
Pugh score, was also analysed. For each patient treated with CLKT, three resolution of ARF was defined as a reduction in serum creatinine to a
2358 M.E. Baccaro et al.
value <1.5 mg/dL; for patients with pretransplant kidney disease, com- before transplantation only in patients with ChildPugh A cirrhosis (six out
plete resolution of ARF was defined when serum creatinine decreased of the 60 patients treated with LT). Hepatitis C recurrence after transplan-
to a final value within 25% of the lowest posttransplant value; tation was treated with interferon and ribavirin in patients with severe re-
(iv) Chronic kidney disease was defined using the criteria of the Na- currence as indicated by clinical and histological criteria (17 of the 60 LT
tional Kidney Foundation [30]. patients and only one of the 20 CLKT patients). Hepatitis B infection was
treated with lamivudine before transplantation and a combination of lami-
Other complications. Selection of donors was based on ABO compatibility, vudine and antihepatitis B immunoglobulin after transplantation.
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 Statistics
the days of survival with a functioning organ without the need for retrans- Student's T-test or MannWhitney test was used to compare continuous
plantation. Renal graft survival was calculated as time elapsed before reach- variables. Categorical variables were analysed using the Chi-square test or
ing chronic dialysis or end-stage renal disease as defined by Kidney Fisher test as appropriate. Probability of survival was calculated using the
Disease Outcomes Quality Initiative Guidelines, from the National Kidney KaplanMeier method, and curves were compared with the log rank test.
Foundation (K/DOQI) stage V (www.kidney.org/professionals/kdoqi/ Results are presented as mean standard deviation unless otherwise spec-
guidelines) or retransplantation. Infectious complications were defined ified. All reported P-values are two-tailed, and values of <0.05 were con-
by the presence of systemic or local signs of infection together with positive sidered statistically significant, except for the univariate analysis of
cultures and/or compatible radiological findings requiring intravenous ad- survival where a P-values <0.1 was considered as significant. All statistical
ministration of antimicrobial agents. Significant hypotension was defined analysis was performed using the SPSS 14.0 program for Windows (SPSS,
as a systolic blood pressure <80 mm Hg or a mean arterial blood pressure of Chicago, IL).
<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 Results
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
Baseline characteristics of the patients
follows: hyperglycaemia, high blood pressure, osteopenia, myopathy, psy- Table 1 shows baseline characteristics of patients included
chosis, ARF associated with high levels of calcineurin inhibitors with or
without any other cause of renal failure, dyslipidaemia, hirsutism, gingival in the study at the time of transplantation. Causes of chron-
hyperplasia, neurotoxicity, hyperuricaemia, cytopenias and severe diar- ic kidney disease in the 20 patients treated with CLKT
rhoea [33]. Hepatitis C infection was treated with interferon and ribavirin 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 2359
in 12 patients (in 10 patients confirmed by kidney biopsy), transplantation was 1.48 0.7 mg/dL in CLKT group
glomerulonephritis in six (IgA glomerulonephritis in four and 1.40 0.4 mg/dL in LT patients (P = ns) (Figure 1).
and membranous nephropathy and focal segmental glo- The prevalence of chronic kidney disease in the CLKT
merulosclerosis in one patient each, all confirmed by kid- group 6 months after transplantation was 25% compared
ney biopsy) and unknown in two patients. While all to 13% in the LT group (P = ns).
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.
Complications after transplantation
Causes of renal failure in these patients were diuretic ther-
apy, type 1 HRS and acute tubular necrosis in one patient Table 3 shows the complications observed within the first
each. Mean pretransplant serum creatinine values in these 6 months after transplantation in the two study groups. In-
three patients were 1.73 0.3 mg/dL. fectious complications were significantly more frequent in
CLKT patients than in LT patients during hospitalisation.
At 6 months after transplantation, the incidence of infec-
Renal failure after transplantation
tion was no longer significantly different between the two
After transplantation, ARF occurred in 11 (55%) patients groups. Shock was more frequent in CLKT patients than in
in the CLKT group during hospitalisation and in 13 (65%) LT patients due to a higher frequency of septic shock that
patients during the first 6 months of follow-up (Table 2). In occurred in 15% of patients receiving CLKT versus none
the LT group, the incidence of ARF was 35% during hos- of the patients in the LT group. Blood transfusion require-
pitalisation and 70% during the first 6 months of follow-up ments were greater in patients treated with CLKT patients
(P = ns vs CLKT). Five patients (25%) needed renal re- compared to the LT group. This was mainly due to higher
placement therapy within the first 6 months after trans- transfusion requirements during the surgical procedure (a
plant compared to only two patients treated with LT median of 5 units for CLKT vs 4 units for LT, P = 0.031).
(3.3%) (P = 0.009). Complications associated with immunosuppressive ther-
Despite the similar incidence of ARF in both groups, the apy were common in both groups of patients. Hypergly-
causes were markedly different (Table 2). In the CLKT caemia or impairment of previous diabetes mellitus
group, 20 episodes of ARF occurred, 50% being due to occurred in 81 and 77% of patients, respectively. De novo
acute tubular necrosis (six episodes) or rejection (four epi- hypertension occurred in 67% of patients in the LT group
sodes). By contrast, in the LT group, 67% of the 62 epi- vs 45% of patients receiving a CLKT (P = ns). ARF asso-
sodes of ARF were attributed to toxicity by calcineurin ciated with high plasma levels of calcineurin inhibitors oc-
inhibitors as suggested by increased serum levels of the curred in 48% of patients in the LT group vs 5% of
drugs and lack of other causes of renal failure. The out- patients in the CLKT group (P < 0.001). Dyslipidaemia,
come of renal function at 6 months was similar between neurotoxicity and transient hypomagnesaemia occurred
both groups. Mean serum creatinine at 6 months after in <15% of patients.

Table 2. Characteristics of posttransplant renal failure in patients treated with combined liverkidney transplantation and patients treated with liver
transplantationa

Combined liverkidney Liver transplantation


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

Acute renal failure


Hospitalisation 11 (55%) 21 (35%) ns
During first 6 months 13 (65%) 42 (70%) ns
Number of episodes 20 62 ns
Causes
CsA/FK 3 (15%) 42 (67%)
ATN 6 (30%) 1 (2%)
Rejection 4 (20%)
Sepsis 3 (15%) 4 (7%)
Otherb 4 (20%) 15 (24%)
Peak of serum creatinine (mg/dL) during 3.9 1.7 (1.97.4) 2 0.5 (1.63.8) 0.002
the first episode of ARF
Dialysis posttransplantation 5 (25%) 2 (3.3%) 0.009

Chronic kidney disease


Incidence 5 (25%) 8 (13%) ns
Serum creatinine at 6 months (mg/dL) 2.47 0.9 (1.53.3) 1.8 0.24 (1.62.2) ns
MDRD (mL/min/1.73 m2) 35 17 (2254) 41 6 (3448) ns

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).
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 The modification of the immunosuppressive protocols
recipients (seven patients 35% and 27 patients 45% after the year 2000 was associated with a slightly higher
at 6 months, respectively, P = ns). Only four patients (20%) frequency of liver rejection (P = 0.04) but not kidney re-
receiving CLKT suffered kidney rejection. Kidney rejec- jection in patients treated with CLKT. No significant
tion occurred in two of the three patients with positive changes were observed in the frequency of liver rejection
cross-match and in only two of the 17 patients with nega- in patients treated with LT.
tive cross-match (P = 0.08). All episodes of liver or kidney Overall surgical reinterventions were more frequent in
rejection responded to treatment, in no case leading to the CLKT group (45 vs 18%, P = 0.034). The higher rate
graft failure. Liver and kidney rejection occurred simulta- of reinterventions in the CLKT group was due to urolog-
neously in only three patients. 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 2361
which developed in half of patients receiving a CLKT. Causes of death in patients with CLKT were infectious
Main causes of urological reintervention were bleeding complications in two patients and cerebrovascular accident
and ureteral stenosis. Vascular and biliary complications and respiratory failure in one patient each. Causes of death
occurred at a similar rate in both groups during follow-up. in patients with LT were infectious complications in two
Patients receiving CLKT had a longer stay in ICU and patients and hepatocellular carcinoma, laryngeal carcino-
total longer in-hospital stay than patients receiving LT (me- ma, multiorgan failure after retransplantation, amyotrophic
dian time, 7 vs 5 days and 29 vs 21 days, respectively, P = lateral sclerosis and acute pancreatitis in one patient each.
0.037 and P = 0.01). Factors associated with an increased risk of death at 1 year
The frequency of complications after transplantation in patients treated with CLKT were serum bilirubin and
was similar between patients with stages 34 of chronic MELD score before transplantation and development of
kidney disease and those with stage 5. When patients shock, infections and ARF during hospitalisation. Both
transplanted during the second half of the study period short- and long-term survival of patients with stage 5 chronic
were compared to those transplanted within the first half, kidney disease were similar to those of patients with stages
significant differences were observed only in the need for 34 (P = ns). The modification of the immunosuppressive
transfusion requirements but not in the frequency of other protocols during the study period did not have a significant
postoperative complications. 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
Graft survival
transplanted within the second part of the study period.
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 = Discussion
0.038) and 75 and 87%, respectively, at 3 years (P = ns).
One patient from the LT group required retransplantation The main findings of the current study are that CLKT in pa-
for cirrhosis due to recurrent hepatitis C infection 2 years tients with cirrhosis and associated chronic kidney disease
after transplantation. Development of cirrhosis due to re- can be performed with an acceptable rate of postoperative
current hepatitis C infection occurred in one patient from complications and a relatively high survival considering that
the CLKT group and nine from the LT group (P = 0.4). these patients have a combination of severe chronic kidney
No CLKT patients reached dialysis at 3 years. No and liver disease before transplantation and are submitted to
CLKT patients required kidney retransplantation during two solid organ transplants. In fact, in the current study, the
the 3-year follow-up. 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
Survival
of similar severity but without chronic kidney disease sub-
Patients treated with CLKT had a 1-year survival that was mitted to LT alone. Three-year survival, although slightly
slightly lower than that of patients treated with LT (80 vs lower in the group of patients treated with CLKT, was not
97%, respectively, P = 0.014). The probability of survival significantly different among the two groups.
at 3 years was also lower in the CLKT group, yet the dif- There are important issues about the design of this study
ference between the two groups did not reach statistical that deserve discussion. First, the validity of the conclu-
significance (75 and 88%, respectively, P = ns) (Figure 2). 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
Fig. 2. Probability of survival of patients treated with combined liver
kidney transplantation (continuous line) and patients treated with liver
are considered candidates for CLKT. Therefore, it was felt
transplantation alone (discontinuous line); values under the graph are that a possible comparative group would be that of a con-
patients at risk. temporary series of patients submitted to LT alone but
2362 M.E. Baccaro et al.
matched for the severity of cirrhosis. This group is also not ever, that not all patients treated with CLKT had very ad-
ideal because patients do not have chronic kidney disease vanced kidney disease, as few patients had stage 3 kidney
and are submitted to only one solid organ transplantation disease. This survival was similar to that reported in previ-
and there might be some differences that are difficult to ous studies of patients treated with CLKT that included not
account for between this group and that of patients treated only patients with cirrhosis but also patients with metabol-
with CLKT, such as the aetiology of cirrhosis or the differ- ic liver diseases without liver failure or polycystic liver and
ent immunosuppressive protocols. Nevertheless, this last kidney disease [2,4,5,9,12,16,17,19,2224,2628]. It is in-
approach was considered better than the other two ap- teresting to note that baseline MELD score was an inde-
proaches and could allow for some orientative assessment pendent predictive factor of posttransplant survival in the
of the outcome in patients treated with CLKT. CLKT group. Graft survival was excellent and comparable
Patients receiving a CLKT had a high frequency of in- to other studies. Liver rejection, as well as the kidney re-
fections and intraoperative bleeding and long ICU and hos- jection rate, was similar to those reported in other studies
pital stays. This increased frequency of complications was [5,7,8,12,16,17,22,24,25,28].
probably responsible for the lower 1-year survival of pa- There is a final aspect of the current investigation that
tients treated with CLKT compared to that of patients trea- needs to be discussed. The current series of patients treated
ted with LT (80 vs 97%, respectively). The increased rate with CLKT does not include patients with HRS. Treatment
of infections in patients with CLKT deserves a specific of patients with cirrhosis and HRS with CLKT instead of LT
comment because infections were associated with 1-year alone is controversial because it increases the number of
mortality in the multivariate analysis. Our results are in kidneys used in patients with cirrhosis and may increase
keeping with those of previous studies suggesting a major the cost of therapy and be associated with higher morbidity
role for sepsis on early posttransplantation mortality in pa- and mortality after transplantation [12,15]. The reason for
tients treated with CLKT [7,9,25,29]. Moreover, infections the lack of patients with HRS treated with CLKT in the cur-
are a more common cause of death in recipients of CLKT rent series is that in our centre, patients with HRS are treated
compared to recipients of kidney transplant alone [8]. Sev- before transplantation with the combination of terlipressin,
eral mechanisms may be accounted for by this increased a vasopressin analogue, and albumin [35,36]. This strategy
frequency of severe infections in patients treated with has the advantage over CLKT of improving renal function
CLKT, including more aggressive immunosuppressive re- before transplantation, which may be associated with an im-
gimens (i.e. induction therapy, addition of MMF), pre- proved outcome after transplantation [37]. Moreover, this
transplant immunosuppresion in some patients due to approach does not increase the number of kidneys required
previous kidney grafts, presence of associated severe renal for treatment of patients with cirrhosis and renal failure.
failure and greater surgical manipulation compared to LT In conclusion, the results of this study show that patients
alone. Whichever the mechanism responsible for the in- with cirrhosis and chronic kidney disease can be submitted
creased frequency of severe infections is, patients submit- to CLKT with an acceptable rate of postoperative compli-
ted to CLKT should be carefully evaluated for the presence cations and have a high survival rate. Therefore, CLKT is
of infections and antibiotic therapy should be instituted an excellent approach to management of patients with cir-
early when there is any suspicion of infection. Patients rhosis and chronic kidney disease.
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- Acknowledgements. Thanks to Marco Pavesi for statistical support.
Grant funding from Fondo de Investigacin Sanitaria; EC07/90077 and
ies and is probably related to the increased surgical manip- PI080126. M.E. Baccaro was supported by a grant from (FRIAT) Instituto
ulation required for CLKT with respect to LT alone [7,9]. Reina Sofia de Investigacin Nefrologica. M.N. Ppin was supported by a
Patients from both CLKT and LT groups had a high and grant from Fondation du Centre Hospitalier de l'Universit de Montral.
similar incidence of ARF during the 6-month period after M. Martin Llahi and Elsa Sola received support from FBBVA (Fundacin
Banco Bilbao Vizcaya Argentaria) Centro de Investigacin Biomedica en
transplantation (65 vs 70%, respectively), yet peak serum Red Enfermedades Hepaticas y Digestivas (CIBERehd) is funded by the
creatinine concentration and need for dialysis were higher Instituto de Salud Carlos III.
in patients from the CLKT group compared to those in the
LT group, indicating a greater severity of renal failure in
Conflict of interest statement. None declared.
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 References
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