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An effective model for predicting acute kidney injury after liver transplantation

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Acute kidney injury (AKI) is a common complication in the early period after liver transplantation (LT), posing an enormous obstacle to treatment efficiency and patient survival. However, the exact influencing factors of AKI are still unclear and a predictive model is desperately required in the clinic. Data of 102 consecutive LTs were reviewed. A model for predicting AKI was established and further validated in a prospective study of 44 patients receiving LT. The incidence of AKI was 32.4%. AKI patients showed a significantly lower survival rate than non-AKI patients. Multivariate analysis demonstrated the independent influencing factors of AKI were preoperative serum creatinine >1.2 mg/dl, intraoperative urine output <or=60 ml/h, intraoperative hypotension status, and intraoperative use of noradrenaline. A model was then established and showed a sensitivity of 75.0%, a specificity of 93.8%, and an accuracy of 88.6% in predicting AKI. High preoperative serum creatinine, low intraoperative urine output, and intraoperative hypotension contribute to the development of AKI, and intraoperative use of noradrenaline serves as a protective factor. The predictive model could potentially facilitate early prediction and surveillance of AKI.
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Hepatobiliary Pancreat Dis IntVol 9No 3 • June 152010 • www.hbpdint.com • 259
AuthorAffiliations: Department of Hepatobiliary and Pancreatic Surgery,
First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
310003,  China  (Xu  X,  Ling Q,  Wei  Q, Wu  J,  Gao  F, He  ZL,  Zhou L  and 
Zheng SS)
CorrespondingAuthor: Shu-Sen  Zheng,  MD,  PhD,  FACS,  Department 
of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang 
University  School  of  Medicine,  Hangzhou  310003,  China  (Tel:  86-571- 
87236567; Fax: 86-571-87236567; Email: zyzss@zju.edu.cn)
© 2010, Hepatobiliary Pancreat Dis Int. All rights reserved.
BACKGROUND: Acute kidney injury (AKI) is a common
complication in the early period after liver transplantation
(LT), posing an enormous obstacle to treatment efficiency
and patient survival. However, the exact influencing factors
of AKI are still unclear and a predictive model is desperately
required in the clinic.
METHODS: Data of 102 consecutive LTs were reviewed. A
model for predicting AKI was established and further
validated in a prospective study of 44 patients receiving LT.
RESULTS: The incidence of AKI was 32.4%. AKI patients
showed a significantly lower survival rate than non-AKI
patients. Multivariate analysis demonstrated the independent
influencing factors of AKI were preoperative serum
creatinine >1.2 mg/dl, intraoperative urine output 60 ml/h,
intraoperative hypotension status, and intraoperative use of
noradrenaline. A model was then established and showed a
sensitivity of 75.0%, a specificity of 93.8% , and an accuracy of
88.6% in predicting AKI.
CONCLUSIONS: High preoperative serum creatinine, low
intraoperative urine output, and intraoperative hypotension
contribute to the development of AKI, and intraoperative use
of noradrenaline serves as a protective factor. The predictive
model could potentially facilitate early prediction and
surveillance of AKI.
(Hepatobiliary Pancreat Dis Int 2010; 9: 259-263)
KEY WORDS: acute kidney injury;
liver transplantation;
risk factors;
complications;
prognosis
Introduction
Acute  kidney  injury  (AKI)  is  the  loss  of  renal 
function  over  a  period  of  hours  to  days  and
reflects  the  entire  spectrum  of  acute  renal 
failure.[1]  It  is  one  of  the  most  common  complications 
after  liver  transplantation  (LT),  especially  in  the  early 
postoperative  period,  and  is  associated  with  a  high 
mortality.[2-8] It is defined as serum creatinine >1.5 mg/dl 
with an increase of 50% above the baseline level or/and 
the  presence  of  need  for  renal  replacement  therapy  in 
the first  week post-LT.[2, 9] The  development of AKI has 
been  associated  with  markedly  increased  costs  and 
consumption  of  health  care  resources  in  the  general 
hospital population and the LT population.[ 5, 10]
Unfortunately,  it  seems  that  the  incidence  of  AKI, 
which  varies  from  17%  to  95%[2 -7]  has  not  shown  a 
significant  decline  with  the  remarkable  improvement 
of  surgical  technique,  the  invention  of  drugs  with  low 
nephrotoxicity  and  the  development  of  perioperative 
management  during the  past  decade,  and  AKI  remains 
an unsolved problem.
The  difficulties  in  early  intervention  contribute 
significantly  to  the  poor  prognosis  of  AKI.  Serum 
creatini ne,  which  is  the  most  importa nt  index  of  renal 
function, is strongly correlated with AKI.[2-5] However, it 
is  apparent  that  preoperative  renal  f unction  alone  may 
be insufficient  to  elucidate  the  underlying  mechanisms 
of  AKI  and  to  predic t  AKI  effect ively.  There  also  have 
been many studies concerning the multifactorial etiology 
of AKI and a variety of preoperative, intraoperative and 
postoperative variables are suggested.[5, 6]
One of the  main  indications for LT in  Asia  is HBV-
related  liver  cirrhosis.  Acc ording  to  an  ea rly  report  on 
a  relatively  small  cohort,  recipients  with  HBV-related 
liver  cirrhosis  might  be  more  susceptible  to  AKI  than 
others.[7]  However,  much  less  is  known  about  the 
incidence  and  the  ex act  factors  influencing  AK I  in  the 
mainland  of  China,  where  the  majority  of  recipients 
receive LT for HBV-related end-stage liver diseases. 
The  present  study  consisted  of  a  retrospective 
An effective model for predicting acute kidney
injury after liver transplantation
Xiao Xu, Qi Ling, Qiang Wei, Jian Wu, Feng Gao, Zeng-Lei He, Lin Zhou and Shu-Sen Zheng
Hangzhou, China
Original Article /
Transplantation
Hepatobiliary & Pancreatic Diseases International
260 • Hepatobiliary Pancreat Dis IntVol 9No 3 • June 152010 • www.hbpdint.com
review  and  a  prospective  identification  in  two  cohorts 
of  patients  with  end-stage  liver  disease  who  received 
LT in our center. The  aim of  the  study was  to evaluate 
the current status  of  AKI in  the first  week  post-LT and 
its  impact  on  patient  survival,  to  identify  the  factors 
critical to  the presence of AKI, and  to  establish  a  valid 
predictive model. The ultimate goal of the present study 
was to identify  patients at great risk for developing AKI 
so  that  effective  rescue  or  protective  strategies  can  be 
promptly undertaken.  
Methods
Retrospective cohort
The  records  of  all  patients  (88  males  and  14  females) 
with  benign end-stage liver disease  who had undergone 
cadaveric  related  LT  at  the  First  Affiliated  Hospital, 
Zhejiang  University  School  of  Medicine,  f rom  January 
2004  until  September  2005  were  retrospectively 
analyzed.  Their  main  indication  for  LT  was  HBV-
related  cirrhosis.  All  of  the  patients  received  a  triple 
immunosuppression regimen consisting of a calcineurin 
inhibitor,  prednisolone  and  mycophenolate  mofetil. 
Patient  characteristics  are  shown  in  Table  1.  Informed 
consent  was  given  by  all  donors  and  recipients  before 
transplantation.  Each  organ  donation  or  transplant 
complied  with  t he g uidelines  of  the  Eth ics  Committee 
of  the  hospital,  the  Organ  Transplant  Committee  of 
Zhejiang Province, and the Declaration of Helsinki.
All  patients underwent  orthotopic LT without veno-
venous  bypass.  To  maintain  an  intraoperative  mean 
arterial pressure above 60 mmHg, some vasoactive drugs 
were  used.  In  some  patients,  continuous  infusion  of 
noradrenalin was initiated at 1 μg/min and subsequently 
raised  to  a  maximum  of  50  μg/min  according  to  the 
clinical response during the anhepatic phase or extended 
to the neohepatic phase. In general, adrenalin was used 
when  noradrenalin  or  high-dose  dopamine  failed  to 
work. Intraoperative hypotension status was defined as a 
systolic blood pressure <90 mmHg for >15 minutes.
AKI was determined by a serum creatinine >1.5 mg/dl 
with an increase of 50% above the baseline level or/and 
the  presence  of  need  for  renal  replacement  therapy  in 
the first  week  post-LT.[11] According to the definition of 
AKI, the patients were divided into an AKI group and a 
non-AKI group. All patients were routinely followed up 
closely at the outpatient clinic.
Validation cohort
To further  evaluate  the clinical  predictive ability of 
the  model  established  in a previous  retrospective  study, 
we  prospectively  investigated  another  cohort  of  44 
adult  patients  with  benign  end-stage  liver  di sease  who 
had  undergone  LT  from  November  2005  to  July  2006 
at  our  center.  Different  from  the  retrospective  cohort, 
the  validation  cohort  were  treated  with  the  piggyback 
technique and tacrolimus. Other perioperative strategies 
were  the  same  as  i n  the  retrospective  study.  The  main 
parameters of the two cohorts are compared in Table 1.
Statistical analysis
The  data  were  analyzed  statistically  using  SPSS, 
version 11.0 (SPSS Inc, Chicago, IL). Descriptive variables 
were  expressed  as  mean±SD  or  median  and  range.  The 
Kaplan-Meier  method  and  the  log-rank  test  were  used 
to assess the impact of AKI on the survival. Appropriate 
cutoff  levels  for  all  potential  influencing  factors  were 
selected  for  their  clinical  significance.  All  the  variables 
were  detected  by  univariate  analysis  and  aP  value  of 
less  than  0.05  was  considered  statistically  significant. 
Variables  with  statistical  significance  were  taken  for  a 
forward stepwise multivariate logistic regression analysis. 
The area under the receiver operating characteristic (ROC) 
curve was generated to assess the model’s discrimination, 
and the  method  of  Hosmer and Lemeshow was  used to 
assess its goodness of fit.
Results
Prevalence of AKI and patient survival
The mean  postoperative follow-up for the  retrospective 
cohort  was  304±214  days  (range  7-686  days).  During 
Characteristics Cohort 1*
  (n=102)
Cohort 2#
  (n=44) P
Age (yr) 45±9 48±10 NS
Gender (male/female) 88/14 41/3 NS
Surgical technique (piggyback/classic) 59/43 44/0 <0.001
MELD score pre-LT 25±9 25±11 NS
Indication
  HBV-related liver cirrhosis 93 41 NS
  HCV-related liver cirrhosis   2   0 NS
  Alcohol-related liver cirrhosis   4   1 NS
  Other   3   2 NS
Immunosuppressive regimen
  Anti-IL2 receptor antibody induction 70 35 NS
  Tacrolimus/Cyclosporine 61/41 44/0 <0.001
Table 1. Patient characteristics
*: Cohort 1, population of retrospective study; #: Cohort 2, population 
of prospective  validation.  NS:  not significant;  MELD: model for  end-
stage liver disease; LT: liver transplantation.  
An effective model for predicting acute kidney injury after liver transplantation
Hepatobiliary Pancreat Dis IntVol 9No 3 • June 152010 • www.hbpdint.com • 261
the first week post-LT, 33 patients (32.4%) developed AKI 
including 10 (9.8%) requiring renal replacement therapy. 
The median time for appearance of AKI was 2 days post-
LT. The median duration of AKI was 17 days (range 7-481 
days). The difference in the  1-year  overall  survival rates 
between  patients  in  the  AKI  and  non-AKI  groups  was 
statistically significant (70.1% vs. 92.3%, P=0.001, Fig. 1).
Clinical features pre-LT
The pre-LT clinical features of the AKI and non-AKI 
groups  showed  differences  in  a ge,  MELD  s core,  seru m 
creatinine,  blood  urea  nitrogen,  serum  sodium,  and 
serum potassium (all P<0.01; Table 2).
Risk factors of AKI
In  our  cohort,  norepinephrine  was  used  intra-
operatively  as  a  protective  drug.  Statistically  significant 
variables  associated  with  AKI  were  revealed  by  the 
univariate analysis. Fourteen parameters were significantly 
associated  with  a  high  risk  of  AKI  (Table  2).  Of  the 
25  patients  with  preoperative  serum  creatinine  >1.2 
mg/dl,  10  including  2  who  needed  renal  replacement 
therapy  developed  hepatorenal syndrome as  defined by 
the  International  Ascites  Club  and  the  other  15  had  a 
slight elevation of serum creatinine (<2 mg/dl) without 
intrinsic kidney disease. 
Predictive model for AKI
Preoperative model
Six  preoperative  parameters  were  subject  to  multi-
variate logistic regression analysis. Serum creatinine >1.2
mg/dl  (odds  ratio  (OR)=8.603,  P<0.001)  and  serum 
sodium
137 mmol/L (OR=3.349, P=0.015) were indepen-
dent  risk  factors  of  AKI.  The  preoperative  model  for 
the prediction of AKI  was established as: -1.961+2.15
(serum  creatinine  >1.2 mg/dl)+1.209×(serum  sodium 
137  mmol/L).  For  predicting  patients  at  ris k  for A KI, 
the area under the ROC curve was 0.765 (Fig. 2). 
Postoperative model
The results of multivariate logistic regression analysis 
are  shown  in  Table  3.  Of  all  14  potential  influencing 
factors analyzed, preoperative serum creatinine >1.2 mg/
dl, intraoperative hypotension status, intraoperative urine 
output 60 ml/h and intraoperative use of noradrenaline 
proved to have the best fit in  our  predictive model: risk 
score=[-2.128+1.109×(preoperative  serum  creatinine 
>1.2  mg/dl)+2.243×(intraoperative  urine  output  60 
Variables AKI P
Yes (n=33) No (n=69)
Preoperative
  Age >50 yr (vs. 50 yr) 16 20   0.045
  MELD score >25 (vs. 25) 21 24   0.006
  Serum creatinine >1.2 mg/dl
    (vs. 1.2 mg/dl)
17   8 <0.001
  Blood urea nitrogen >23 mg/dl
    (vs. 23 mg/dl) 
14 11   0.004
  Serum sodium 137 mmol/L
    (vs. >137 mmol/L)
21 25   0.009
  Serum potassium >5.0 mmol/L
    (vs. 5.0 mmol/L)
  5   1   0.013
Intraoperative
  Red blood cells >15 U (vs. 15 U) 26 34   0.005
  Fresh-frozen plasma >3000 ml
    (vs. 3000 ml)
18 21   0.019
  Platelets >10 U (vs. 10 U) 20 25   0.020
  Blood loss >5000 ml (vs. 5000 ml) 16 13   0.002
  Urine output 60 ml/h (vs. >60 ml/h) 23 14 <0.001
  Adrenaline >2.3 mg (vs. 2.3 mg) 19 16   0.001
  Hypotension status
    (vs. no hypotension status)
17 11 <0.001
  Use of noradrenaline
    (vs. no use of noradrenaline)
  2 22   0.004
Table 2. Univariate analysis of influencing factors for AKI
MELD: model for end-stage liver disease.
Fig. 1.Comparison  of  cumulative patient survival between the 
AKI group (broken line) and the non-AKI group (solid line); the 
log-rank test, P=0.001.
Fig. 2. Area under ROC curve of the preoperative model (broken 
line, 0.765) and postoperative model (solid line, 0.908).
Hepatobiliary & Pancreatic Diseases International
262 • Hepatobiliary Pancreat Dis IntVol 9No 3 • June 152010 • www.hbpdint.com
ml/h)+1.542×(intraoperative hypotension status)-2.46
(intraoperative  use  of  noradrenaline)].  Probability  of 
AKI=EXP (risk score)/[1+EXP (risk score)].
The  model  discriminated  well  (area  under  ROC 
curve:  0.908,  Fig.  2)  and  fitted  excellently  (P=0.971 
to  reject  model  fit).  Considering  both  sensitivity  and 
specificity, we selected the risk score as a cutoff of -0.2 to 
predict AKI. This implied that patients with a risk score 
-0.2  (at  high  risk)  were  more  likely  to  develop  AKI 
than those with a risk score <-0.2 (at low risk). 
The  consequent  prospective  evaluation  using  the 
established  model  showed  good  predictive  results. 
According to the predictive rule, 9 of 11 patients at high 
risk  developed  AKI,  and  30  of  33  patients  at  low  risk 
did not develop AKI.  This  model  obtained a sensitivity 
of  75.0%  (9/12),  a  specificity  of  93.8%  (30/32)  and  an 
accuracy of 88.6% (39/44). 
Discussion
In  this  study,  we  examined  renal  function  in  the  early 
period post-LT in patients most of whom had hepatitis B 
related  liver  disease.  Our  retrospective  study  confirmed 
the  previous  studies  that  AKI  has  a  relatively  high 
incidence(32.4%) and has a marked negative impact on 
the short-term and long-term survival of patients. Thus it 
would be better if there were an effective model for early 
prediction of AKI. 
A  preoperative  model  could  identify  patients  going 
into LT who are at risk for AKI. However, we found it was 
difficult to predict the development of AKI based on the 
preoperative  data  alone,  as  the  predictive  ability  of  the 
preoperative  model  was  far  from  desirable  (area  under 
ROC  curve  <0.8).  The  etiology  of  AKI  is  multifactorial 
and  the  potential  risk  factors  include  preoperative, 
intraoperative  and  postoperative  factors.[2-7]  Our  finding 
that  most  AKI  cases  appeared  within  3  days  post-LT 
suggested  that  it  might  be  mainly  associated  with  the 
preoperative  and  intraoperative  conditions.  This  study 
demonstrated  that  patients  at  high  risk  could  be  clearly 
discriminated  from  those  at  low  risk  for  developing 
AKI  by  a  predictive  model  established  on  the  basis  of 
one  preoperative  variable  (high  serum  creatinine  level) 
and  three  intraoperative  variables  (low  urine  output, 
hypotension  status  and  nonuse  of  noradrenalin).  Using
this model, we can rapidly and simply assess the natural 
course  of  renal  function  post-LT  and  take  prompt 
strategies for the prevention and treatment of AKI.
It has frequently been mentioned in Western reports 
that  preoperative  impairment  of  renal  function  plays 
a  crucial  role  in  the  occurrence  of  AKI.[2-5]  Serum 
creatinine  has  traditionally  been  considered  as  a  simple
and cheap marker for assessing renal function in clinical 
practice.  Nevertheless,  patients  with  end-stage  liver 
disease always present high levels of serum creatinine.[3, 12]
Even  a  mild  elevation  of  preoperative  serum  creatinine 
level  (1.0-1.5  mg/dl)  may  forebode  poor  renal  function 
post-LT.[13] To better evaluate preoperative renal function, 
we  tried  different  serum  creatinine  levels  between  1.0 
and 1.5 mg/dl for analysis and finally selected >1.2 mg/dl 
as the best cutoff value for the threshold of preoperative 
renal dysfunction. 
Intraoperative  injury to the kidneys could be induced
by  unstable  hemodynamics  (massive  blood  loss,  hypo-
tension status,  low  urine output, and  large  requirement 
for  blood  products),  surgical  technique  or  nephrotoxic 
drugs.[14-16]  Our  data  indicated  that  massive  blood  loss, 
major  blood  product  transfusion,  hypotension  status, 
low  urine  output  and  moderate  or  even  high  doses  of 
vasopressors  were  significantly  related  to  AKI.  To  some 
extent,  intraoperative  massive  blood  loss  is  inevitable 
in  patients  with  refractory  disturbance  of  coagulation 
and severe varices.[17] Large amountsof blood loss result 
in  unstable  hemodynamics  and  inadequate  vital  organ 
perfusion,  reflected  by  hypotension  and  low  urine 
output. Fluid transfusion and vasopressors are definitely 
required under these conditions, and  some drugs  might 
aggravate  poor  kidney  perfusion.  Of  particular  interest,
noradrenaline,  an  available and  common agent in  clinic 
use,  was  found  to  be  significantly  associated  with  a 
reduced  incidence of  AKI,  which  has  not  been  reported. 
Recently, both clinical and animal studies have indicated 
that  noradrenaline  functions  are  effective  not  only  in 
elevating  arterial  blood  pressure,  but  also  in  improving 
renal  blood  flow  and  urine  output  in  vasodilated 
conditions  such  as  septic  shock.[18-20]  Recipients  with 
cirrhosis  present  characteristic  hemodynamic  changes, 
including  low  arterial  blood  pressure  and  increased 
cardiac output before and during operation, which might 
be similar to septic shock.[20, 21]Further studies such as a 
randomized and double-blind clinical trial are desperately 
required  to  certify  the  potential  renal  protective 
function of noradrenalin in LT. 
Variables P OR 95% CI
Preoperative serum creatinine >1.2 mg/dl
  (vs. 1.2 mg/dl)
  0.045 3.031  0.896-10.25
Intraoperative urine output 60 ml/h
  (vs. >60 ml/h)
<0.001 9.423 2.932-30.28
Intraoperative hypotension status   0.016 4.673 1.335-16.36
Intraoperative use of noradrenaline
  (vs. no use of noradrenaline)
  0.010 0.085 0.013-0.548
Table 3. Multivariate analysis of influencing factors for AKI
OR: odds ratio; CI: confidence interval.
An effective model for predicting acute kidney injury after liver transplantation
Hepatobiliary Pancreat Dis IntVol 9No 3 • June 152010 • www.hbpdint.com • 263
The  actual  impact  on  the  development  of  AKI  of 
other  potential  influencing  factors  such  as  age,  serum 
sodium  and  serum  potassium  is  still  not  well  defined. 
Although  the  univariate  analysis  did  not  find  that  the 
immunosuppressive  regimen  is  a  r isk  factor  of  AKI,  in 
our experience  the  application of calcineurin inhibitors 
should be postponed if the calculated risk score is  above 
-0.2  according  to  this  predictive  model.  Veno-venous 
bypass  has  been  abandoned  since  2001  at  our  center 
because  our  previous  study  did  not  find  any  positive 
effect from this technique on renal function.[22]
In conclusion, AKI remains a common complication 
after  LT  with  a  poor  prognosis  among  patients  with 
HBV-related  liver  diseases.  In  China,  the  preoperative 
serum  creatinine,  intraoperative  urine  flow,  intra-
operative  hypotension  status  and  intraoperative  use 
of  noradrenalin  are  strongly  associated  with  AKI. 
The  predictive  model  established  on  the  basis  of 
these  four  independent  influencing  factors  may  be  a 
reliable  and  effective  tool  to  identify  patients  at  high 
risk  for  developing  AKI,  and  thus  prompt  salvaging 
interventions  are  required.  Further  well-designed 
studies  are  needed  to  clearly describe the  strengths  and 
limitations of this predictive model.
Funding: This study was supported by a grant from the Projects of 
Ministry of Public Health (No. 20082006).
Ethical approval: Not needed.
Contributors: XX  proposed  the  study  and  wrote  the  first  draft. 
All  authors  contributed  to  the  design  and  interpretation  of  the 
study and to further drafts. ZSS is the guarantor. 
Competing interest: No  benefits  in any  form  have  been received 
or  will  be  received  from  a  commercial  party  related  directly  or 
indirectly to the subject of this article.
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Received May 14, 2009
Accepted after revision November 6, 2009
... Reported risk factors for post-LTx AKI are demonstrated in Table 2. Higher pretransplant SCr [11,[23][24][25][32][33][34][35], high body mass index (BMI) [39,64,66,67], high MELD/MELD-Na score [23,[39][40][41][42][43][44][45][46][47][48][49], intraoperative blood loss and perioperative blood transfusion [18,25,39,48,54,65], high APACHE II score [25,43,48,55], hypotension and vasopressor requirement [18,24,48,54], cold and warm ischemia time [14,35,78], graft dysfunction [11,40,53], post-reperfusion syndrome [20,64,66,75,78], infection prior to transplant [25,45,48], and hypoalbuminemia [18,64,66] were consistently identified as important risk factors for Post-LTx AKI. ...
... AKI was associated with prolonged intensive care (ICU) and hospital stay [17,18,23,24,29,32,35,40,42,44,48,49,53,61,64,75,78] (Table 3). Table 2. Higher pretransplant SCr [11,[23][24][25][32][33][34][35], high body mass index (BMI) [39,64,66,67], high MELD/MELD-Na score [23,[39][40][41][42][43][44][45][46][47][48][49], intraoperative blood loss and perioperative blood transfusion [18,25,39,48,54,65], high APACHE II score [25,43,48,55], hypotension and vasopressor requirement [18,24,48,54], cold and warm ischemia time [14,35,78], graft dysfunction [11,40,53], post-reperfusion syndrome [20,64,66,75,78], infection prior to transplant [25,45,48], and hypoalbuminemia [18,64,66] were consistently identified as important risk factors for Post-LTx AKI. ...
... A diamond data marker represents the overall rate from each included study (square data marker) and 95% confidence interval. Table 2. Higher pretransplant SCr [11,[23][24][25][32][33][34][35], high body mass index (BMI) [39,64,66,67], high MELD/MELD-Na score [23,[39][40][41][42][43][44][45][46][47][48][49], intraoperative blood loss and perioperative blood transfusion [18,25,39,48,54,65], high APACHE II score [25,43,48,55], hypotension and vasopressor requirement [18,24,48,54], cold and warm ischemia time [14,35,78], graft dysfunction [11,40,53], post-reperfusion syndrome [20,64,66,75,78], infection prior to transplant [25,45,48], and hypoalbuminemia [18,64,66] were consistently identified as important risk factors for Post-LTx AKI. ...
Article
Full-text available
Background: The study's aim was to summarize the incidence and impacts of post-liver transplant (LTx) acute kidney injury (AKI) on outcomes after LTx. Methods: A literature search was performed using the MEDLINE, EMBASE and Cochrane Databases from inception until December 2018 to identify studies assessing the incidence of AKI (using a standard AKI definition) in adult patients undergoing LTx. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, the generic inverse variance approach of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018100664). Results: Thirty-eight cohort studies, with a total of 13,422 LTx patients, were enrolled. Overall, the pooled estimated incidence rates of post-LTx AKI and severe AKI requiring renal replacement therapy (RRT) were 40.7% (95% CI: 35.4%⁻46.2%) and 7.7% (95% CI: 5.1%⁻11.4%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of post-LTx AKI (p = 0.81). The pooled estimated in-hospital or 30-day mortality, and 1-year mortality rates of patients with post-LTx AKI were 16.5% (95% CI: 10.8%⁻24.3%) and 31.1% (95% CI: 22.4%⁻41.5%), respectively. Post-LTx AKI and severe AKI requiring RRT were associated with significantly higher mortality with pooled ORs of 2.96 (95% CI: 2.32⁻3.77) and 8.15 (95%CI: 4.52⁻14.69), respectively. Compared to those without post-LTx AKI, recipients with post-LTx AKI had significantly increased risk of liver graft failure and chronic kidney disease with pooled ORs of 3.76 (95% CI: 1.56⁻9.03) and 2.35 (95% CI: 1.53⁻3.61), respectively. Conclusion: The overall estimated incidence rates of post-LTx AKI and severe AKI requiring RRT are 40.8% and 7.0%, respectively. There are significant associations of post-LTx AKI with increased mortality and graft failure after transplantation. Furthermore, the incidence of post-LTx AKI has remained stable over the ten years of the study.
... Our study builds on prior work incorporating intraoperative variables into the prediction model. Prior studies have characterized the effect of major classes of intraoperative variables, including blood transfusion, [25,49] hemodynamic variables (most notably, intraoperative hypotension), [25,[50][51][52] vasopressor/ inotropic support, [25,51,52] surgical technique, [25] laboratory values, [12,25,52] and hypovolemia. [26,30] Our study failed to show an association between intraoperative MAP or intraoperative transfusion (packed red blood cells [pRBC], FFP, or cryoprecipitate) with the primary outcome. ...
... Our study builds on prior work incorporating intraoperative variables into the prediction model. Prior studies have characterized the effect of major classes of intraoperative variables, including blood transfusion, [25,49] hemodynamic variables (most notably, intraoperative hypotension), [25,[50][51][52] vasopressor/ inotropic support, [25,51,52] surgical technique, [25] laboratory values, [12,25,52] and hypovolemia. [26,30] Our study failed to show an association between intraoperative MAP or intraoperative transfusion (packed red blood cells [pRBC], FFP, or cryoprecipitate) with the primary outcome. ...
Article
Full-text available
Background and aims: Acute kidney injury (AKI) is one of the most common complications of liver transplantation (LT). We aimed to examine the impact of intraoperative management on risk for AKI following liver transplantation. Methods: In this retrospective observational study, we linked data from the electronic health record with standardized transplant outcomes. Our primary outcome was Stage 2 or 3 AKI as defined by Kidney Disease Improving Global Outcomes (KDIGO) guidelines within the first 7-days of liver transplantation. We used logistic regression models to test the hypothesis that the addition of intraoperative variables, including inotropic/vasopressor administration, transfusion requirements, and hemodynamic markers improves our ability to predict AKI following LT. We also examined the impact of post-operative AKI on mortality. Results: Of the 598 adult, primary liver transplant recipients included in our study, 43% (n=255) were diagnosed with AKI within the first 7-postoperative days. Several preoperative and intraoperative intraoperative variables including: (i) electrolyte/acid-base balance disorder (ICD-9: 253.6 or 276.x, ICD-10: E22.2 or E87.x, where x is any digit)) (adjusted odds ratio (aOR)=1.917, 95% CI=1.280-2.869, P=0.002) (ii) preoperative anemia (aOR=2.612, 95% CI=1.405-4.854, P=0.002), (iii) low serum albumin (aOR=0.576, 95% CI=0.410-0.808, P=0.001), increased potassium value during reperfusion (aOR=1.513, 95% CI=1.103-2.077, P=0.01), and lactate during reperfusion (aOR=1.081, 95% CI=1.003-1.166, P=0.04) were associated with post transplant AKI. New dialysis requirement within the first 7-days postoperatively predicted the post-transplant mortality. Conclusions: Our study identified significant association between several potentially modifiable variables with post transplant AKI. The addition of intraoperative data did not improve overall model discrimination.
... However, they can be classified into three categories: pre-transplantation, perioperative and post-operative. We identified these predictive factors by uni-or multivariate analysis from 101 observational studies published between 1996 and 2019 [8,10,[36][37][38][40][41][42][43][44][45][46]48,53,56,[60][61][62][63][64]70,71,73,[76][77][78][79][80][81][82][83][84][85][86][87][89][90][91][92][93][94][95][96][97]104,[106][107][108][111][112][113] (Figure 1). ...
... The severity of liver impairment (high MELD score) has been identified as a risk factor for post-transplantation CKD [112]. Similarly, an elevated Child-Pugh score, hypoalbuminemia, hepato-renal syndrome, hepatic encephalopathy and the need for TIPS are associated with both the development of AKI and the risk of progression to CKD [16,18,26,61,64,81,84,94,115,116,122,130]. ...
Article
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One-third of patients with cirrhosis present kidney failure (AKI and CKD). It has multifactorial causes and a harmful effect on morbidity and mortality before and after liver transplantation. Kidney function does not improve in all patients after liver transplantation, and liver transplant recipients are at a high risk of developing chronic kidney disease. The causes of renal dysfunction can be divided into three groups: pre-operative, perioperative and post-operative factors. To date, there is no consensus on the modality to evaluate the risk of chronic kidney disease after liver transplantation, or for its prevention. In this narrative review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease in order to establish a risk categorization for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this context, and highlight the indications of combined liver–kidney transplantation.
... 7,8 In the last decade, there have been many efforts to improve perioperative management and to enhance the use of intervention drugs with less nephrotoxicity. 9 Still, there remains a lack of understanding about the risk factors leading to AKI after OLT. ...
... AKI patients had a longer ICU stay, 4 days (3-7) vs. 3 days (2-4), p = 0.001, as well as longer overall hospital stay, 16 days (9-26) vs. 10 days (8)(9)(10)(11)(12)(13)(14), p = 0.001 than non AKI patients, respectively. ...
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Introduction. The aim of this study is to evaluate the risk factors for acute kidney injury (AKI) and 30-day mortality after liver transplantation. Material and methods. This is a retrospective cohort of consecutive adults undergoing orthotopic liver transplantation (OLT) at a referral hospital in Brazil, from January 2013 to January 2014. Risk factors for AKI and death were investigated. Results. A total 134 patients were included, with median age of 56 years. AKI was found in 46.7% of patients in the first 72 h after OLT. Risk factors for AKI were: viral hepatitis (OR 2.9, 95% CI = 1.2-7), warm ischemia time (OR 1.1, 95% CI = 1.01-1.2) and serum lactate (OR 1.3, 95%CI = 1.02-1.89). The length of intensive care unit (ICU) stay was longer in AKI group: 4 (3-7) days vs. 3 (2-4) days (p = 0.001), as well as overall hospitalization stay: 16 (9-26) days vs. 10 (8-14) days (p = 0.001). The 30-day mortality was 15%. AKI was an independent risk factor for mortality (OR 4.3, 95% CI = 1.3-14.6). MELD-Na ≥ 22 was a predictor for hemodialysis need (OR 8.4, 95%CI = 1.5-46.5). Chronic kidney disease (CKD) was found in 36 patients (56.2% of AKI patients). Conclusions. Viral hepatitis, longer warm ischemia time and high levels of serum lactate are risk factors for AKI after OLT. AKI is a risk factor for death and can lead to CKD in a high percentage of patients after OLT. A high MELD-Na score is a predictor for hemodialysis need.
... The anhepatic phase is a unique and pivotal time during liver transplantation, and acid-base balance disorder, hemodynamic instability and renal congestion are much more pronounced (1,14). Xu and colleagues (32) reported that low urine volume was significantly related to AKI, which reflects inadequate renal perfusion. A recent study demonstrated that an intraoperative urine volume < 0.5 ml kg −1 h −1 was associated with postoperative AKI in a major abdominal surgery population (33). ...
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Acute kidney injury (AKI) after liver transplantation (LT) is a common complication, and its development is thought to be multifactorial. We aimed to investigate potential risk factors and build a model to identify high-risk patients. A total of 199 LT patients were enrolled and each patient data was collected from the electronic medical records. Our primary outcome was postoperative AKI as diagnosed and classified by the KDIGO criteria. A least absolute shrinkage and selection operating algorithm and multivariate logistic regression were utilized to select factors and construct the model. Discrimination and calibration were used to estimate the model performance. Decision curve analysis (DCA) was applied to assess the clinical application value. Five variables were identified as independent predictors for post-LT AKI, including whole blood serum lymphocyte count, RBC count, serum sodium, insulin dosage and anhepatic phase urine volume. The nomogram model showed excellent discrimination with an AUC of 0.817 (95% CI: 0.758–0.876) in the training set. The DCA showed that at a threshold probability between 1% and 70%, using this model clinically may add more benefit. In conclusion, we developed an easy-to-use tool to calculate the risk of post-LT AKI. This model may help clinicians identify high-risk patients.
... The in-hospital mortality rate was 22.4% ( Knowledge of postoperative risk factors associated with AKI in liver transplantation patients is scarce: this has mostly been studied in the pre and intraoperative periods. 23,27,[28][29][30] It is currently believed that bleeding that leads to transfusion requirements during the surgical procedure is associated with AKI, especially a need for red blood cells and cryoprecipitate. 6,22,30 In our study, the need for blood transfusion at any time during the ICU stay was associated with an odds ratio eight times higher for the development of AKI KDIGO 2 or 3. ...
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Background: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. Objective: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. Design and setting: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. Methods: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). Results: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). Conclusion: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.
... They assumed that noradrenaline use may prevent more sustained hypotension and has a protective role in restoring blood pressure among hypotensive patients with vasodilation and could mask the intraoperative hypotension effects. 31,39 Similar to our findings, previous studies provided evidence that pretransplant hypoalbuminemia is a significant independent predictor that contributes to the progression of post-LTx AKI. 40,41 There are several explanations for this phenomenon. ...
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Objectives: Acute kidney injury is a frequent complication of liver transplant. Here, we assessed the rate and contributing factors of acute kidney injury and need for renal replacement therapy in patients undergoing liver transplant at a transplant center in Tehran, Iran. Material and methods: We identified all patients who underwent liver transplant at the Imam Khomeini Hospital Complex from March 2018 to March 2019 and who were followed for 3 months after transplant. Acute kidney injury was defined based on the Acute Kidney Injury Network criteria. We collected demographic and pretransplant, intraoperative, and posttransplant data. Univariable and multivariable models were applied to explore independent risk factors for acute kidney injury incidence and need for renal replacement therapy. Results: Our study included 173 deceased donor liver transplant recipients. Rates of incidence of acute kidney injury and need for renal replacement therapy were 68.2% and 14.5%, respectively. The 3-month mortality rate among those with severe and mild or moderate acute kidney injury was 44.0% (14/25) and 9.7% (9/ 93), respectively (P < .001). Multivariable analyses indicated that serum albumin (relative risk of 0.55; 95% confidence interval, 0.34-0.87; P = .021), baseline serum creatinine (relative risk of 2.11; 95% confidence interval, 1.56-2.90; P = .037), and intraoperative mean arterial pressure (relative risk of 0.76; 95% confidence interval, 0.63-0.82; P = .008) were independent factors for predicting posttransplant acute kidney injury. Independent risk factors for requiring renal replacement therapy were pretransplant serum creatinine (relative risk of 1.99; 95% confidence interval, 1.89-4.47; P = .044) and intraoperative vasopressor infusion (relative risk of 1.41; 95% confidence interval, 1.38-2.00; P = .021). Conclusions: We found a high incidence of acute kidney injury among liver transplant recipients in our center. There was a significant association between severity of acute kidney injury and 3-month and in-hospital mortality.
... As this would introduce an overestimation of the weight of the VISION cohort, the article with the most severe outcome parameter 22 was included. Fourteen articles [24][25][26][27][28][29][30][31][32][33][34][35][36][37] were excluded based on low study quality based on the NOS scale ( Fig. 1). ...
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Background: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality. Methods: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity. Results: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent. Conclusion: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic.
... Importantly, there are many other risk factors for kidney insufficiency in orthotopic LT patients. For example, several intraoperative factors have been reported to significantly predict postoperative kidney function, including intraoperative hypotension (odds ratio [OR] 4.7; P=0.016), and the need for noradrenaline (OR 0.085; P=0.010) [21]. As our study did not specifically include assessment of risk factors for renal insufficiency, this is an area for future research. ...
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BACKGROUND Delaying initiation of tacrolimus after liver transplantation (LT) is a potential renal-sparing strategy. We assessed safety and efficacy of delayed initiation of prolonged-release tacrolimus (PR-T) in de novo LT. MATERIAL AND METHODS This was a single-center, single-arm, prospective, 12-month observational study of hepatitis C virus-negative orthotopic LT patients. Immunosuppression included PR-T (initially 0.1 or 0.2 mg/kg/day) initiated on Day 3 post LT, basiliximab (20 mg) on post-transplantation Day 0 and Day 4, and intraoperative corticosteroids (500 mg). Patients received maintenance corticosteroids and mycophenolate mofetil (MMF) according to center protocol. MMF dose was adjusted according to thrombocyte count. The primary endpoint was the estimated glomerular filtration rate (eGFR) measured using the Modification of Diet in Renal Disease 4-variable formula at 12 months. Secondary endpoints included biopsy-confirmed acute rejection (BCAR) and dialysis requirement. Adverse events were recorded. RESULTS Sixty-nine patients (mean age 55.0 years) were included. Most patients started MMF on Day 1 (60.9%) or Day 2 (10.1%), and PR-T on Day 3 (55.1%) or Day 4 (29.0%). Mean tacrolimus trough levels (ng/mL) were: Day 7, 9.5±6.3; Day 10, 9.4±5.4; Month 1, 8.0±3.1; Month 3, 7.8±3.7; Month 6, 8.0±4.1; and Month 12, 7.2±3.1. Mean 12-month eGFR was 77.2±24.5 mL/min/1.73 m2; 72.5% of patients had eGFR >60 mL/min/1.73 m² at 12 months; 89.9% had no eGFR measurements <40 mL/min/1.73 m² during the study. Renal insufficiency (any eGFR <60 mL/min/1.73 m²) was diagnosed in 27.5% of patients; one patient required dialysis. There were no BCAR episodes; the infection rate was 36.2%, and 3 patients died. Overall, 19 patients (27.5%) developed de novo diabetes mellitus, 18 patients (26.1%) had hypercholesterolemia, and 12 patients (17.4%) had hypertriglyceridemia. CONCLUSIONS Quadruple therapy with delayed administration of PR-T was well tolerated and efficacious, and was associated with acceptable renal function over 12 months.
Article
Résumé L’insuffisance rénale concerne plus d’un tiers des patients cirrhotiques. Elle est d’origine multifactorielle et impacte fortement la morbi-mortalité de ces patients avant, mais également après, transplantation hépatique. L’amélioration de la fonction rénale en post-greffe n’est pas systématique et les transplantés hépatiques ont un risque accru de maladie rénale chronique à plus ou moins court terme. Les étiologies responsables de la dégradation de la fonction rénale sont nombreuses et se regroupent en facteurs préopératoires, comme la fonction rénale du jour de la greffe, en facteurs peropératoires et postopératoires. À l’heure actuelle, aucun consensus n’est admis sur les modalités d’évaluation du risque comme sur la prévention de l’insuffisance rénale chronique en post-transplantation. Nous proposons, dans ce travail, une revue de la littérature sur le devenir de la fonction rénale en post-greffe et les facteurs pronostiques d’insuffisance rénale chronique afin de déterminer une stratification du risque pour chaque patient. Dans un second temps, nous développons les options thérapeutiques actuelles pour prévenir au mieux la dégradation de la fonction rénale chez ces patients, et nous discutons les indications d’une greffe combinée foie–rein.
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Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.
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A Multivariate analysis was done in all patients who developed post operative ARF, during the period 1990–1995 to determine the etiological spectrum and to identify various variables affecting the outcome. Of 140 patients (110 operated at SGPGI and 30 operated outside) 116 underwent elective surgery. The different types of surgery leading to ARF were urosurgery (3.5%), open heart surgery (32.9%), gastrosurgery (16.4%), pancreatic surgery (9.3%), obstetrical surgery (3.6%) and others (2.8%). The incidence of ARF in SGPGI patients was highest in pancreatic surgery group (8.2%) followed by open heart surgery (3%). The different etiological factors responsible for ARF were perioperative hypotension (67.1%), sepsis (63.6%) and exposure to nephrotoxic drugs (29.3%). Sixty-four patients (45.7%) required dialysis. The overall mortality was 45% The mortality was highest in patients who underwent open heart surgery (89.1%) followed by pancreatic surgery (84.6%). The factors associated with high mortality, other than the type of surgery, were preoperative hypotension (p <0.05), oliguria (p <0.01), need for dialysis (p <0.05) and multiorgan failure (p <0.001). AM following emergency surgery had poor outcome, though not statistically significant. Perioperative sepsis (p <0.05) and preoperative use of aminoglycoside (p <0.05) were significantly higher in patients operated outside SGPGI. This was associated with higher incidence of ARF. Thus we conclude that presence of multiorgan failure, oligoanuria, preoperative hypotension and need far dialysis are poor prognostic markers in ARF following surgery.
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Acute renal failure (ARF) is a common and severe complication after liver transplantation (LT). The aim of this study was to ascertain the impact of ARF requiring dialysis in the outcome of LT and to analyze the risk factors leading to this event in the early post-operative period. From October 1988 to December 1994, 172 LT were performed in 158 patients. Postoperative ARF occurred in 88 transplants (51.1%) during the early postoperative period: mild ARF was found in 46 (serum creatinine 1.5-3 mg/dl), moderate ARF in 12 (serum creatinine > 3 mg/dl) and severe ARF in 30 (serum creatinine > 3 mg/dl with dialysis requirement). Preoperative, intraoperative, and postoperative variables were studied, comparing patients presenting severe ARF with the remaining patients. Postoperative mortality in the dialysed group was much higher than in the non-dialysis group (50% vs. 13.4%)(p < 0.001) and 1-yr actuarial graft survival was 73.4% for the non-dialysed group compared with 40.9% for the dialysed group (p < 0.05). Among 38 variables investigated, only two factors had independent prognostic value in multivariate analysis: preoperative serum creatinine > 1.5 mg/dl (OR = 4.4, p = 0.006) and graft dysfunction grades III-IV (OR = 8.9, p = 0.001). In conclusion, ARF is a severe complication post-LT; its appearance could be predicted in patients with pre-transplant renal dysfunction, severe graft dysfunction, or both. However, in many cases renal function may revert to normal if treated aggressively with early dialysis support.
Article
More candidates with creatinine levels >or= 2 mg/dL have undergone liver transplantation (LT) since the implementation of Model for End-Stage Liver Disease (MELD)-based allocation. These candidates have higher posttransplant mortality. This study examined the effect of serum creatinine on survival benefit among candidates undergoing LT. Scientific Registry of Transplant Recipients data were analyzed for adult LT candidates listed between September 2001 and December 2006 (n = 38,899). The effect of serum creatinine on survival benefit (contrast between waitlist and post-LT mortality rates) was assessed by sequential stratification, an extension of Cox regression. At the same MELD score, serum creatinine was inversely associated with survival benefit within certain defined MELD categories. The survival benefit significantly decreased as creatinine increased for candidates with MELD scores of 15 to 17 or 24 to 40 at LT (MELD scores of 15-17, P < 0.0001; MELD scores of 24-40, P = 0.04). Renal replacement therapy at LT was also associated with significantly decreased LT benefit for patients with MELD scores of 21 to 23 (P = 0.04) or 24 to 26 (P = 0.01). In conclusion, serum creatinine at LT significantly affects survival benefit for patients with MELD scores of 15 to 17 or 24 to 40. Given the same MELD score, patients with higher creatinine levels receive less benefit on average, and the relative ranking of a large number of wait-listed candidates with MELD scores of 15 to 17 or 24 to 40 would be markedly affected if these findings were incorporated into the allocation policy.
Article
Acute kidney injury (AKI) has significant prognostic implications for long-term outcomes in patients undergoing liver transplantation. In several retrospective studies, perioperative variables have been associated with AKI. These variables have been mainly associated with changes in creatinine concentrations over several days or months post-transplantation. To better define AKI, new markers have become available that help to identify patients at risk for renal injury within hours of a triggering insult. We prospectively enrolled liver transplant patients at our institutions to evaluate neutrophil gelatinase-associated lipocalin (NGAL), a marker of early renal injury, as a surrogate for AKI in patients undergoing liver transplantation. Blood was prospectively collected at predetermined time points from 59 patients at 2 institutions. The electronic anesthesia records and the hospital computer data system were reviewed for perioperative variables. Data collection included patient demographics, intraoperative variables such as fluid management, transfusion requirements, hemodynamics, and urine output. Subsequently, patients were grouped according to the presence of risk for developing AKI as defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. The difference between the NGAL concentration 2 hours after reperfusion and the baseline NGAL concentration was predictive of AKI in all patients, including patients with preexisting renal dysfunction. In patients with creatinine concentrations less than 1.5 mg/dL, a single NGAL determination 2 hours after reperfusion of the liver was associated with the development of AKI. Total occlusion of the inferior vena cava was associated with AKI. In conclusion, NGAL concentrations obtained during surgery were highly associated with postoperative AKI in patients undergoing liver transplantation. These findings will allow the design of larger interventional studies. Our findings regarding the impact of surgical techniques and glucose require validation in larger studies.
Article
The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.
Article
Orthotopic liver transplantation (OLT) is the only effective treatment for end-stage liver disease. Although most patients do well and are discharged promptly, some require prolonged length of stay (PLOS). The prevalence of PLOS, associated factors, and their impact on survival are not well defined. We reviewed our adult OLT database for patients who survived > 30 days. PLOS was defined as hospitalization > 30 days following OLT. Of 521 OLT recipients, 68 (13%) had PLOS with a median duration of 50 days versus only 10 days for patients discharged within 30 days. Significant differences in pre-OLT variables between patients with and without PLOS included the mean wait list time (P = 0.001), hospitalization at the time of OLT (P = 0.001), and prior OLT (P = 0.041). Factors independently associated with PLOS included intensive care unit status at the time of OLT [odds ratio (OR), 4; 95% confidence interval (CI), 1.6-10.4], OLT prior to Model for End-Stage Liver Disease implementation (OR, 2.27; 95% CI, 1.04-5.26), in-hospital post-OLT bacterial infection (OR, 9.34; 95% CI, 4.65-18.86), gastrointestinal bleeding (OR, 4.34; 95% CI, 1.4-14.08), renal failure (OR, 10.86; 95% CI, 5.07-23.25), and allograft rejection (OR, 3.7; 95% CI, 1.23-11.11). One-year graft survival and patient survival were significantly less in those with PLOS (for both, P < 0.0001). Among PLOS patients, factors independently associated with increased 1-year mortality were donor age (OR, 1.07; 95% CI, 1.009-1.13), primary diagnosis of hepatitis C virus (OR, 6.89; 95% CI, 1.40-34.48), in-hospital post-OLT bacterial infection (OR, 13.3; 95% CI, 2.11-83.33), and cardiac complications (OR, 20.4; 95% CI, 1.51-250; c-statistic for the model, 0.85). In conclusion, PLOS following OLT is associated with a significant decrease in survival despite a marked increase in cost and resource utilization. Efforts to modify those factors that contribute to PLOS may reduce this event, improve survival, and reduce OLT-associated costs.
Article
To determine the incidence, prevalence, and prognostic value of preoperative and postoperative renal dysfunction occurring in adults undergoing orthotopic liver transplantation, the records of 102 consecutive adults who underwent orthotopic liver transplantation using cyclosporin A were reviewed. Renal dysfunction was defined arbitrarily as an increase in creatinine or blood urea nitrogen, or both, to 1.5 and 50 mg/dl, respectively, in patients previously having normal renal function or a 50% increase in either creatinine or blood urea nitrogen in patients with preexisting renal dysfunction. Twenty-six of the 102 patients had renal dysfunction before orthotopic liver transplantation. Sixty-eight of the 102 patients studied experienced an episode of renal impairment after orthotopic liver transplantation. Forty-nine of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 36 cases at 32 +/- 6 days after orthotopic liver transplantation. Using multivariate analysis, cirrhosis of a noncholestatic nature was found to be an independent predictor of early renal impairment. Trough blood cyclosporin A levels measured by radioimmunoassay were higher in those who experienced early renal impairment or late renal impairment than in those who did not (p less than 0.05). Several factors capable of adversely influencing renal function (nephrotoxic drugs, shock, and graft failure) other than cyclosporin A were present also in half of the patients who developed late renal impairment. Overall, 25 patients died. Multivariate analyses identified serious postoperative infection, graft failure, and preoperative renal dysfunction to be independent predictors of mortality.
Article
To assess the ability of preoperative information to predict intraoperative blood transfusion requirements in adult orthotopic liver transplantation. Retrospective review. Liver transplantation program in a referral center. 583 sequential adult patients undergoing orthotopic liver transplantation. Preoperative variables with a previously demonstrated relationship to intraoperative transfusion were identified from the literature. These variables were then collected retrospectively from 583 consecutive liver transplantations. Relationships between these and intraoperative blood transfusion requirements were examined by both univariate analyses and multiple linear regression analysis. Univariate analysis revealed significant associations between blood transfused and the following preoperative variables: age, gender, diagnosis, presence of grade 3 or 4 encephalopathy, pseudocholinesterase, creatinine, bilirubin, mean pulmonary artery pressure, activated partial thromboplastin time, and platelet count. Multiple linear regression analysis with correction for diagnosis identified age, creatinine, bilirubin, and pseudocholinesterase as independent predictors; for the final model r(2) = 0.22. Preoperative variables are poor predictors of intraoperative transfusion requirements even when significant associations exist, identifying a small proportion of the variability observed. A predictive approach based on this method would be too inaccurate to be of clinical use. The majority of the variability in transfusion requirements during liver transplantation most likely results from intraoperative and donor organ factors.
Article
Despite increasingly sophisticated critical care, the mortality of septic shock remains elevated. Accordingly, care remains supportive. Volume resuscitation combined with vasopressor support remains the standard of care as adjuvant therapy, and many consider dopamine to be the pressor of choice. Because of fear of excessive vasoconstriction, norepinephrine is considered to be deleterious. The present study was designed to identify factors associated with outcome in a cohort of septic shock patients. Special attention was paid to hemodynamic management and to the choice of vasopressor used, to determine whether the use of norepinephrine was associated with increased mortality. Prospective, observational, cohort study. Intensive care unit of a university hospital. Ninety-seven adult patients with septic shock. Data from these patients were examined to select variables independently and significantly associated with outcome during the hospital stay. Nineteen clinical, biological, and hemodynamic variables were collected at study entry or during the first 48-72 hrs and analyzed for each patient. A stepwise logistic regression analysis and a model building strategy were used to identify variables independently and significantly associated with outcome. The overall hospital mortality was 73% (71 patients). Five variables were significantly associated with outcome. One factor was strongly associated with a favorable outcome: the use of norepinephrine as part of the hemodynamic support of the patients. The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk = 0.68; 95% confidence interval = 0.54-0.87) than the 40 patients treated with vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine). Four variables were associated with a poor outcome and significantly higher hospital mortality: pneumonia as a cause of septic shock (82% vs. 61%, p < .03; relative risk = 1.47; 95% confidence interval = 1.07-1.77), organ system failure index < or = 3 (92% vs. 60%, p < .001; relative risk = 1.47; 95% confidence interval = 1.17-1.82), low urine output at entry to the study (88% vs. 60%, p < .01; relative risk = 1.44; 95% confidence interval = 1.06-1.87), and admission blood lactate concentration > 4 mmol/L (91% vs. 63%, p < .01; relative risk = 1.60; 95% confidence interval = 1.27-1.84). Our results indicate that the use of norepinephrine as part of hemodynamic management may influence outcome favorably in septic shock patients. The data contradict the notion that norepinephrine potentiates end-organ hypoperfusion, thereby contributing to increased mortality. However, the present study suffers from some limitation because of its nonrandomized, open-label, observational design. Hence, a randomized clinical trial is needed to clearly establish that norepinephrine improves mortality of patients with septic shock, as compared with high-dose dopamine or epinephrine. Pneumonia as the cause of septic shock, high blood lactate concentration, and low urine output on admission are strong indicators of a poor prognosis. Multiple organ failure is confirmed as a reliable predictor of mortality in septic patients.