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Apel ef al. Critical Care 2013, 17:R298 
http://ccforum.eom/content/17/6/R298 



CRITICAL CARE 



RESEARCH Open Access 



End-Stage renal disease and outconne in a 
surgical intensive care unit 

Mareike Apel\ Vivian PL Maia\ Mohamed Zeidan^, Claudia Schinkoethe^, Gunter Wolf^, Konrad Reinhart^ 
and Yasser Sakr^" 



Abstract 

Introduction: End-stage renal disease (ESRD) is associated witin an increased propensity for critical illness, but 
whether ESRD is independently associated with a greater risk of death after major surgical procedures is unclear. 

Methods: This was a retrospective analysis of prospectively collected data from all adult (>18 years) patients 
admitted to a 50-bed surgical intensive care unit (ICU) between January 2004 and January 2009. ESRD was defined 
as the need for chronic peritoneal dialysis or hemodialysis for at least 6 weeks prior to ICU admission. We used 
multivariable logistic regression analysis and propensity-score matching to adjust for possible confounders. 

Results: In total, 12,938 adult patients were admitted during the study period; 199 patients had ESRD at ICU 
admission, giving a prevalence of 1.5%. Patients with ESRD were more likely to be male (72.9% versus 63.0%, 
P = 0.004) and had higher severity scores, a higher incidence of diabetes mellitus and cirrhosis, and a lower 
incidence of cancer at ICU admission than those without ESRD. Patients with ESRD were more likely to have any 
type of organ failure at ICU admission and during the ICU stay. Patients with ESRD had higher ICU and hospital 
mortality rates (23.1% and 31.2% versus 5.5% and 10.0%, respectively, P <0.001 pairwise) and longer ICU length of 
stay (2 (1 to 7) versus 1 (1 to 3) days, P <0.001). In multivariable logistic regression analysis, ESRD was independently 
associated with a greater risk of in-hospital death (odds ratio = 3.84, 95% confidence interval 2.68 to 5.5, P <0.001). 
In 199 pairs of patients, hematologic and hepatic failures were more prevalent, ICU and hospital mortality rates were 
higher (23.1% versus 15.1% and 31.2% versus 19.1%, P <0.05 pairwise), and ICU length of stay was longer (2 (1 to 7) 
versus 1 (1 to 7) days, P <0.001) in patients with ESRD. 

Conclusions: In this large cohort of surgical ICU patients, presence of ESRD at ICU admission was associated with 
greater morbidity and mortality and independently associated with a greater risk of in-hospital death. Our data can 
be useful in preoperative risk stratification. 



Introduction 

The prevalence of chronic kidney disease is increasing 
worldwide [1,2]. The progressive nature of this chronic 
health problem and the ensuing end-stage renal disease 
(ESRD) creates a considerable burden on global health- 
care resources [3]. The annual incidence of ESRD has 
doubled over the past decade to reach about 100 to 336 
new patients per million population [3,4]. Patients with 
ESRD have a high propensity for critical illness and 
require intensive care unit (ICU) admission 25 times 
more frequently than patients without ESRD [5,6]. The 

* Correspondence: yasser.sakr{S)med.uni-jena.de 

^Department of Anesthesiology and Intensive Care, Friedrich-Schiller-University 

Hospital, Erianger Allee 103, 07743 Jena, Germany 

Full list of author information is available at the end of the article 



prevalence of ERSD in ICU patients ranges between 1.3% 
and 7.3% and its presence is associated with a higher 
degree of morbidity and mortality in these patients [5,7,8]. 

Whether ESRD is associated per se with a higher risk 
in critically ill patients, independent of the severity and 
nature of the critical illness, remains unclear. In a large 
cohort of patients admitted to 170 adult ICU patients in 
England, Wales, and Northern Ireland, ESRD was associ- 
ated with a higher risk of in-hospital death after adjusting 
for possible confounders [7]. This result was not, however, 
confirmed in a large database of ESRD patients admitted 
to 11 Canadian ICUs [5]. However, these studies [5,7] 
included mixed medical and surgical ICU patients, with 
a high proportion of medical admissions. Data on the 
possible impact of ESRD on outcome after major surgical 



© 2013 Apel et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative 
BIOIVIGCI CCntrBl commons Attribution License (httpy/creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and 
reproduction in any medium, provided the original work is properly cited. 



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procedures are scarce. Such information may be useful 
in preoperative risk stratification of surgical patients and 
hence could improve clinical decision making in these 
patients. It may also be interesting to identify the patterns 
of non-renal organ dysfunction/failure and predictors 
of poor outcome in ESRD patients admitted to the ICU 
after major surgical procedures. The aims of our study 
were, therefore, to test the hypothesis that ESRD is 
independently associated with a higher risk of death 
after major surgical procedures and to identify possible 
risk factors for in-hospital death in these patients. 

Materials and methods 

The study was approved by the institutional review board 
of Friedrich Schiller University Hospital (Jena, Germany). 
Informed consent was waived because of the retrospective, 
anonymous nature of the analysis. We included all adult 
(>18 years old) patients admitted to our 50-bed surgical 
ICU from January 2004 to January 2009. For patients 
admitted to the ICU more than once, only the first 
admission was considered. 

Data collection 

Data were collected from vital sign monitors, ventilators, 
and infusion pumps and automatically recorded by a 
patient data management system (Copra System GmbH, 
Sasbachwalden, Germany). This system provides staff 
with complete electronic documentation, order entry (for 
example, medications), and direct access to laboratory 
results. Documentation in our ICU is exclusively electronic. 
Data recorded prospectively on admission include age, 
gender, serum parameters, primary and secondary ad- 
mission diagnoses, and surgical procedures. Primary 
and secondary diagnoses are recorded by using codes 
from the International Classification of Diseases- 10. 

The Simplified Acute Physiology Score II (SAPS II) [9] 
was calculated on admission, and the Sequential Organ 
Failure Assessment (SOFA) score [10] was calculated daily 
by the physician in charge of the patient by using a special 
sheet. A plausibility check of the automatically transmitted 
data was performed by the attending physician before 
calculating the final scores. In sedated patients, the 
Glasgow Coma Scale prior to initiation of sedation was 
considered. Hospital mortality and hospital discharge 
dates were available for all patients from the electronic 
hospital records. 

Definitions 

ESRD was defined as the need for chronic peritoneal 
dialysis or hemodialysis for at least 6 weeks prior to the 
time of admission to the ICU. In patients with ESRD 
following acute renal failure, 3 months were required 
to establish the diagnosis of ESRD. Diabetes mellitus 
refers to types 1 and 2 diabetes mellitus. SO¥A^^^ was 



defined as the maximum SOFA score recorded during 
the ICU stay, and SOFA mean as the mean value during 
the ICU stay [10]. 

Statistical analysis 

Data were analyzed by using SPSS 13.0 for Windows 
(SPSS Inc., Chicago, IL, USA) and SAS version 9.1.3 
software (SAS Institute Inc., Gary, NC, USA). The 
Kolmogorov-Smirnov test was used to verify the normality 
of distribution of continuous variables. Non-parametric 
tests of comparison were used for variables evaluated as 
not being normally distributed. Difference testing between 
groups was performed by using a WUcoxon test, Mann- 
Whitney U test, chi-square test, and Fisher's exact test 
as appropriate. 

To define the possible factors associated with poor 
outcome in the whole cohort we performed a multivari- 
able logistic regression analysis, with in-hospital death 
as the dependent variable. The variables considered for 
this analysis were age, sex, SAPS II, SOFA subscores, type 
of surgery, emergency admissions, and ESRD. Colinearity 
between variables was excluded before modeling (R >0.6), 
and none of the covariates was colinear. A Hosmer and 
Lemeshow goodness-of-fit test was performed, and odds 
ratios (ORs) with 95% confidence intervals (CIs) were 
computed. 

To identify the possible risk factors associated with 
in-hospital death in patients with ESRD, we performed a 
forward stepwise multivariable logistic regression analysis 
with in-hospital death as the dependent variable. The 
variables considered for this analysis were age, sex, 
SAPS II, SOFA subscores, type of surgery, emergency 
admissions, the etiology of ESRD, residual urine output 
(<500 mL/day and >500 mL/day), and the type of access 
for dialysis (arterio-venous shunt, central venous catheter, 
and peritoneal catheter). Covariates were entered in the 
model {P <0.2 on a univariate basis) step-by-step and 
retained in the model if the P value was less than 0.2 
after multivariable adjustment. 

Propensity scores [11] were obtained through logistic 
regression of patient characteristics on ESRD status 
(Additional file 1: Table SI). The propensity score was 
calculated as the probability based on the final model. 
A greedy matching technique was used to match indi- 
vidual ESRD patients with those who did not have 
ESRD, based on propensity scores. The best-matched 
propensity score was five digits long. Once a match 
was made, the control patient was removed from the 
pool. This process was then repeated by using four-digit 
matching, then three-digit matching, and so on. The 
process proceeded sequentially to a single-digit match 
on propensity score. Differences between matched pairs 
were tested by using a paired t test, Wilcoxon test, and 
McNemar X2 statistics, as appropriate. 



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All Statistics were two-tailed. A P value of less than 0.05 
was considered to be significant. Continuous variables are 
presented as mean ± standard deviation or median (25% 
to 75% interquartile range) and categorical variables as 
number and percentage, unless otherwise indicated. 

Results 

Characteristics of the study cohort 

During the study period, 12,938 patients were admitted 
to our surgical ICU (mean age = 62.5 years (standard 
deviation 14.9), male = 63.2%). The characteristics of the 
study groups on admission to the ICU are shown in 
Table 1. The prevalence of ESRD on admission to the 
ICU was 1.5% (n = 199). Diabetic (40.2%) and hypertensive 
(23.6%) nephropathies were the most common causes 
of ESRD, followed by inflammatory conditions (chronic 
glomerulonephritis, interstitial nephritis, chronic pyelo- 
nephritis, and nephritic syndrome: 16.5%), congenital 
diseases (renal hypoplasia and polycystic kidney: 6.5%), 
and neoplasm (4.0%). Among patients with ESRD, 117 
(58.8%) were anuric, whereas 82 patients (41.2%) had 
residual diuresis prior to ICU admission (< or >500 mL/ 
day in 40 and 42 patients, respectively). The predominant 
mode of dialysis in patients with ESRD was hemodialysis 
(98.0%); in 64.3% of cases, this was performed through 
an arterio-venous shunt and in 34% through a right 



atrial catheter. Only four patients (2%) were treated by 
peritoneal dialysis. 

Patients with ESRD were more likely to be male (72.9% 
vs. 63.0%, P = 0.004), had higher severity scores, and had a 
greater incidence of diabetes mellitus and cirrhosis and 
lower incidence of cancer on admission to the ICU than 
those without ESRD (Table 1). Gastrointestinal surgery 
was more common (29.6% vs. 21.4%, P <0.001) and 
neurosurgical procedures less common (15.9% vs. 4.0%, 
P <0.001) in patients with ESRD compared with those 
without ESRD. Serum urea, serum creatinine, leukocyte 
count, and serum potassium were higher whereas hema- 
tocrit values, platelet counts, pH, serum bicarbonate, and 
serum sodium levels were lower in patients with ESRD 
than those without ESRD (Additional file 1: Table S2). 

Morbidity and mortality 

The most prevalent organ failures on admission to the ICU 
and at any time during the ICU stay were cardiovascular 
(46.2% and 49.5%) followed by central nervous system 
(36.7% and 42.4%) and respiratory (24.1% and 30.9%) 
failures. Patients with ESRD were more likely to have 
any type of organ failure on admission to the ICU and 
at any time during the ICU stay than those without 
ESRD (Table 2). Notably, hematologic failure occurred 
up to 4 times more often in patients with ESRD (21.6% 



Table 1 Characteristics of the study group on admission to the intensive care unit according to the presence of 
end-stage renal disease 





All patients 


ESRD 


No ESRD 


P value 




(n = 12,938) 


(n = 199) 


(n = 12,739) 




Age in years, mean ± SD 


62.5 ± 14.9 


624 ± 13.1 


62.5 ± 14.9 


0,509 


Male, n (%) 


8,176 (63.2) 


145 (72.9) 


8,031 (63.0) 


0.004 


Severity scores, mean ± SD 










SAPS II 


38.3 ± 18.6 


56.3 ±20.5 


38.0 ± 184 


<0.001 


SOFA 


6.0 ± 3.9 


1 0.6 ± 4.2 


6.0 ± 3.8 


<0.001 


SOFA (without renal points) 


57 ±3.6 


7.5 ±4.2 


5.6 ± 3.6 


<0.001 


Type of surgery, n (%) 










Cardlothoracic 


5,409 (41 .8) 


84 (42.2) 


5,325 (41.8) 


0,145 


Gastrointestinal 


2,780 (21.5) 


59 (29.6) 


2,721 (21.4) 


<0.001 


Neurosurgery 


2,030 (1 5.7) 


8 (4.0) 


2,022 (15.9) 


<0.001 


Trauma 


523 (4.0) 


9 (4.5) 


514 (4.0) 


0.229 


Other surgery^ 


2,196 (16.9) 


39 (19.6) 


2,157 (16.9) 


0,001 


Comorbidities, n (%) 










Diabetes mellitus 


6,749 (52.2) 


148 (74.4) 


6,601 (51.8) 


<0.001 


Arterial hypertension 


2,785 (21.5) 


47 (23.6) 


2,738 (21.5) 


0.469 


Cancer 


2,501 (19.3) 


19 (9.5) 


2,482 (19.5) 


<0.001 


Heart failure 


1,645 (127) 


33 (16.6) 


1,612 (12.7) 


0.099 


Cirrhosis 


472 (3.6) 


19 (9.5) 


453 (3.6) 


<0.001 



^Renal/urinary tract, obstetric/gynecologic, ear, nose, and throat, and maxillofacial surgeries. ESRD, end-stage renal disease; SAPS II, Simplified Acute Physiology 
Score II; SD, standard deviation; SOFA, Sequential Organ Failure Assessment. 



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Table 2 Morbidity and mortality of the study group according to the presence of end-stage renal disease 



All patients 
(n = 1 2,938) 



ESRD 
(n = 199) 



No ESRD 
(n = 12,739) 



P value 



Organ failure, n (%) 

- On admission to the ICU 
Cardiovascular 

CNS 

Respiratory 
Renal 

Hematologic 
Hepatic 

- At any time during ICU stay 
Cardiovascular 

CNS 

Respiratory 
Renal 

Hematologic 
Hepatic 
SOFApnax scores, mean ± SD 
SOFA^,, 

SOFAmax without renal points 
ICU mortality, n (%) 
Hospital mortality, n (%) 
ICU LOS in days, median (IQR) 



5,974 (46.2) 
4,747 (36.7) 
3,120 (24.1) 
390 (3.0) 
309 (2.4) 
215 (1.7) 

6,407 (49.5) 
5,489 (42.4) 
3,992 (30.9) 
630 (4.9) 
618 (4.8) 
405 (3.1) 

6.5 ±43 
5.7 ±3.6 
746 (5.8) 
1,330 (10.3) 
1 (1-3) 



1 35 (67.8) 
90 (45.2) 
68 (34.2) 
199 (100) 
27 (13.6) 
15 (7.5) 

144 (72.4) 
112 (56.3) 
88 (44.2) 
199 (100) 
43 (21.6) 
24 (12.1) 

1 1 .5 ± 4.6 
7.5 ± 4.2 
46 (23.1) 
62 (31.2) 
2 (1-7) 



5,839 (45.8) 
4,657 (36.6) 
3,052 (24.0) 
237 (1.9) 
282 (2.2) 
200 (1.6) 

6,263 (49.2) 
5,377 (42.2) 
3,904 (30.6) 
431 (3.4) 
575 (4.5) 
381 (3.0) 

64 ± 4.2 
5.6 ± 3.6 
700 (5.5) 
1,268 (10.0) 
1 (1-3) 



<0.001 
0.012 
0.001 
<0.001 
<0.001 
<0.001 

<0.001 
<0.001 
<0.001 
<0.001 
<0.001 
<0.001 

<0.001 
<0.001 
<0.001 
<0.001 
<0.001 



CNS, central nervous system; ESRD, end-stage renal disease; ICU, intensive care unit; IQR, interquartile range; LOS, length of stay; SD, standard deviation; SOFA, 
Sequential Organ Failure Assessment; SOFAmax, maximum Sequential Organ Failure Assessment score recorded during the intensive care unit stay. 



VS. 4.5%, P <0.001) than in other patients. Consequently, 
SOFAniax with (11.5 ± 4.6 vs. 6.4 ± 4.2, P <0.001) or with- 
out (7.5 ± 4.2 VS. 5.6 ± 3.6, P <0.001) renal points was 
higher in patients with ESRD than in those without ESRD. 

The overall ICU and hospital mortality rates were 5.8% 
and 10.3%, respectively, and the median ICU length of stay 
(LOS) was 1 day (interquartile range: 1-3 day). Patients 
with ESRD had higher ICU and hospital mortality rates 
(23.1% and 31.2% vs. 5.5% and 10%, respectively, P <0.001 
pairwise) and longer ICU LOS (2 (1-7) vs. 1 (1-3) days, 
P <0.001) than those without ESRD. The most common 
causes of death in the ICU were sepsis-related multiorgan 
failure (52.2%), bleeding complications (15.2%), cardio- 
genic shock (13.0%), and electrolyte disturbances (10.9%). 



Multivariable analysis and propensity score matching 

In multivariable logistic regression analysis with hospital 
mortality as the dependent variable, ESRD was independ- 
ently associated with a greater risk of in-hospital death 
(OR = 3.84, 95% CI: 2.68-5.5, P <0.001) after adjustment 
for age, gender, comorbidities, SAPS II, type of surgery, 
and SOFA subscores on admission to the ICU (Additional 
file 1: Table S3). 



In 199 pairs of patients matched according to a propen- 
sity score, age, sex, comorbid conditions, severity scores, 
and non-renal organ failure on admission to the ICU were 
similar between patients with and those without ESRD 
(Table 3). The type of surgery prior to admission to the 
ICU was similar between the matched groups apart from 
a lower prevalence of neurosurgical procedures in patients 
with ESRD than in those who did not have ESRD (4.0% vs. 
14.6%, P <0.001). Although the prevalence of respiratory, 
cardiovascular, and central nervous system organ failures 
was similar between the matched groups throughout the 
ICU stay, hematologic (21.6% vs. 11.6%, P = 0.015) and 
hepatic (12.1% vs. 8.5%, P = 0.03) organ failures were more 
prevalent in patients with ESRD than in their propensity 
score-matched pairs (Table 4). ICU and hospital mortality 
rates were higher (23.1% vs. 15.1% and 31.2% vs 19.1%, 
respectively, P <0.05 pairwise) and ICU LOS was longer 
(2 (1-7) vs. 1 (1-7) days, P <0.001) in patients with ESRD 
compared with their propensity score-matched pairs. 

Predictors of poor outcome in patients with ESRD 

In a multivariable analysis in patients with ESRD (Additional 
file 1: Table S4), the use of central venous catheters for 
dialysis (OR: 3.30, 95% CI: 1.36-8.04, P = 0.009) and higher 



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Table 3 Characteristics of the propensity score-matched 
groups on admission to the intensive care unit 





ESRD 


No ESRD 


P value 




(n = 199) 


(n = 199) 




Age in years, mean ± SD 


62.4 ± 13.1 


61 4 ±14.4 


0.524 


Male, n (%) 


145 (72.9) 


161 (80.9) 


0.057 


Severity scores, mean ± SD 








SAPS II 


41.95 ± 19.35 


40.39 ± 1 7.22 


0.422 


SOFA" 


7.47 ± 4.20 


7.04 ±3.52 


0.458 


Comorbidities, n (%) 








Diabetes mellitus 


148 (74.4) 


141 (70.9) 


0.431 


Arterial hypertension 


47 (23.6) 


33 (16.6) 


0.080 


Heart failure 


33 (16.6) 


21 (10.6) 


0.079 


Cirrhosis 


1 9 (9.5) 


20 (10.1) 


0.866 


Cancer 


19 (9.5) 


23 (11.6) 


0.514 


Type of surgery on 
admission day, n (%) 








Cardiothoracic 


84 (42.2) 


83 (41.7) 


0.919 


Digestive 


59 (29.6) 


53 (26.6) 


0.504 


Neurosurgery 


8 (4.0) 


29 (14.6) 


<0.001 


Trauma 


9 (4.5) 


8 (4.0) 


0.804 


Others 


39 (19.6) 


26 (13.1) 


0.122 


Organ failure, n {%) 








Cardiovascular 


1 35 (67.8) 


1 26 (63.3) 


0.342 


CNS 


90 (45.2) 


76 (38.2) 


0.155 


Respiratory 


68 (34.2) 


55 (27.6) 


0.158 


Hematologic 


27 (13.6) 


15 (7.5) 


0.050 


Hepatic 


15 (7.5) 


9 (4.5) 


0.206 



Table 4 Sequential Organ Failure Assessment scores and 
organ failure during the intensive care unit stay, and 
mortality rates in the propensity score-matched subgroups 



^Without renal points. CNS, central nervous system; 
disease; SAPS II, Simplified Acute Physiology Score I 
SOFA, Sequential Organ Failure Assessment. 



ESRD, end-stage renal 
1; SD, standard deviation; 



hepatic SOFA subscores (OR = 1.60, 95% CI: 1.07-2.4, 
P = 0.022) were independently associated with an in- 
creased risk of in-hospital death. Female sex, admission 
after cardiac versus non-cardiac procedures, and residual 
urinary output of greater than 500 mL versus anuria were 
independently associated with a lower risk of in-hospital 
death (Additional file 1: Table S4). 

Discussion 

The main findings of our study were that (1) ESRD was 
associated with a high incidence of comorbidities and 
high degree of severity of illness on admission to the ICU; 
(2) patients with ESRD were more likely to have any 
type of organ failure during the ICU stay than those 
without ESRD, especially hematologic failure; (3) ESRD 
was independently associated with a greater risk of 
in-hospital death in multivariable analysis; (4) mortality 
rates were higher, ICU LOS was longer, and hematologic 
and hepatic organ failures were more prevalent in patients 





ESRD 
(n = 199) 


No ESRD 
(n = 199) 


P 

V3lu6 


SOFAmax scores, mean ± SD 








SOFA^ax (with renal points) 


1 1 45 ± 4.62 


8.31 ±441 


<0.001 


SOFA^ax (without renal points) 


8.61 ±4.96 


7.79 ±4.1 3 


0.166 


Organ failure, n (%) 








Renal 


199 (100.0) 


7 (3.5) 


<0.001 


Cardiovascular 


144 (72.4) 


134 (67.3) 


0516 


CNS 


1 1 2 (563) 


100 (50.3) 


0.144 


Respiratory 


88 (44.2) 


79 (39.7) 


0.658 


Hematologic 


43 (21.6) 


23 (11.6) 


0.015 


Hepatic 


24 (12.1) 


1 7 (8.5) 


0.030 


ICU LOS in days, median (lOR) 


2 (1-7) 


1 (1-7) 


<0.001 


Hospital mortality, n (%) 


62 (31.2) 


38 (19.1) 


0.006 


ICU mortalit/, n (%) 


46 (23.1) 


30 (15.1) 


0.041 



CNS, central nervous system; ESRD, end-stage renal disease; ICU, intensive care 
unit; IQR, interquartile range; LOS, length of stay; SD, standard deviation; SOFA, 
Sequential Organ Failure Assessment; SOFAmax, maximum Sequential Organ 
Failure Assessment score recorded during the intensive care unit stay. 

with ESRD compared with propensity score-matched 
pairs; and (5) the use of central venous vascular access 
and higher hepatic SOFA subscores were independently 
associated with increased risk of in-hospital death, whereas 
female sex, admission after cardiac procedures, and residual 
urinary output of greater than 500 mL versus anuria were 
independently associated with decreased risk of in-hospital 
death in patients with ESRD. 

The prevalence of ESRD on admission to the ICU in 
our study was 1.5%, which lies within the lower 
spectrum of the prevalence rates reported in previous 
studies that included mostly medical ICU patients [5,7,8]. 
Indeed, the presence of ESRD may have influenced the 
decision to perform surgical procedures in our hospital, 
especially those performed on an elective basis. For this 
reason, in addition to the single-center nature of the 
study, we cannot extrapolate these data to other cohorts. 

As expected, we found that ESRD was associated with 
a high incidence of comorbidities on admission to the 
ICU. This can be explained by the contribution of these 
comorbidities to the pathophysiology of ESRD, especially 
diabetes mellitus, which is the most common cause of 
ESRD in developed countries [3]. The higher prevalence 
of liver cirrhosis in patients with ESRD compared with 
others may be attributed to the high incidence of hepa- 
titis C and D in these patients [11]. Male sex is also well 
recognized as a risk factor for chronic kidney disease 
[3,12,13], which explains the predominance of men 
(72.9%) among the patients with ESRD in our study. In 
addition, the most frequent underlying diseases were 



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diabetes and hypertension, both of which suggest at least 
an alteration of vascular control. This association with a 
vascular injury related to ESRD might have contributed 
to the worth outcome in these patients. 

In our study, organ failure occurred more frequently 
in patients with ESRD than in those without ESRD. 
Impaired renal function is a major risk factor for 
cardiovascular morbidity and mortality [14]. Several 
factors may contribute to the increased incidence of 
cardio-respiratory dysfunction in patients with ESRD, 
including left ventricular hypertrophy, rapid electrolyte 
shifts during dialysis, QT dispersion, sympathetic over- 
activity, and deposition of calcium-phosphate precipitants 
within arteries [14,15]. Acute pulmonary infections, peri- 
operative volume overload, excessive inter-dialytic weight 
gain, and primary cardiac events may also contribute to 
respiratory failure in patients with ESRD. The higher 
prevalence of hepatic failure in our patients may be 
explained by the higher incidence of liver cirrhosis in 
these patients compared with those without ESRD. The 
impairment of renal elimination of hypnotic and sedative 
agents given perioperatively in patients with ESRD [14] 
may explain the high occurrence of neurological failure in 
these patients. Interestingly, we found that hematologic 
failure occurred up to 4 times more frequently in patients 
with ESRD than in those without. Patients on chronic 
dialysis have abnormalities in the cellular and plasma 
systems regulating blood homeostasis, which may be 
caused by uremic plasma associated with exposure of 
blood to the hemodialysis membranes and tubing causing 
increased thrombotic and bleeding risks [16]. Platelet 
dysfunction is a common occurrence in patients with 
ESRD, as a result of intrinsic platelet abnormalities and 
impaired platelet-vessel wall interaction, and is probably 
responsible for the hemorrhagic tendencies in these 
patients [16]. Recently, Darlington and colleagues [17] 
reported that 42.9% of patients with ESRD had a functional 
hypocoagulable state, using thromboelastography, com- 
pared with 8.9% in the control group. 

In our study, ESRD was independently associated with a 
greater risk of in-hospital death after adjusting for possible 
confounders. We were able to confirm this finding by 
using two statistical techniques, namely, logistic regression 
multivariable analysis and propensity score matching. 
To the best of our knowledge, our study is the first to 
investigate this issue in a purely surgical cohort of ICU 
patients. Our data support the notion that ESRD per se 
may contribute, independently of other comorbidities 
and severity of illness, to the risk of in-hospital death 
after major surgical procedures. Several small studies 
[8,18-21] and two large multicenter studies [5,7] have 
reported contradictory results, with some confirming 
[6-8,18] and others [5,19-21] disputing the independent 
association between ESRD and poor outcome from critical 



illness. The discrepancy in the results of these studies may 
be explained by differences in case mix and local practices. 
Indeed, these studies included mixed populations of 
medical and surgical ICU patients (65% to 73% non- 
surgical). Nevertheless, our results are in agreement with 
the results of a large multicenter study that included 
270,972 adult ICU patients admitted to 170 ICUs in the 
UK (56% non-surgical cases) and that reported that ESRD 
was associated with a greater risk of in-hospital death 
after adjusting for baseline characteristics, severity of 
illness, and comorbidities [7]. Interestingly, these authors 
[7] reported that the ESRD population had higher mortal- 
ity rates with lower numbers of non-renal organ failures, 
confirming the independent influence of ESRD on the 
risk of death in these patients. 

The poor outcome in patients with ESRD is probably 
multifactorial. These patients likely lack physiological 
reserve, as evident from the high severity of illness 
and the associated comorbid conditions on admission 
to the ICU. Patients with ESRD may also have disturbed 
immunological responses, favoring infectious complications 
[7]. Perioperative patient management, especially volume 
administration, may also have contributed to the unfavor- 
able outcome. The need for vascular access to provide 
hemodialysis in the ICU postoperatively and the frequent 
occurrence of electrolyte disturbances in patients with 
ERDS are other risk factors that may have influenced 
outcomes. The results of the propensity score matching 
in our study provide more insight about the possible 
mechanisms by which ESRD may influence outcome in 
patients with ESRD. Although the 199 pairs were well 
matched according to baseline characteristics, severity 
of illness, type of surgery, and the frequency of individual 
non-renal organ failures on admission to the ICU, patients 
with ESRD had a higher prevalence of hematologic and 
hepatic failures in the ICU. Hematologic failure occurred 
almost twice as often in patients with ESRD as in their 
propensity score-matched pairs. As discussed above, 
hematologic disturbances in patients with ESRD may 
be associated with an increased risk of both bleeding 
and thrombosis [16], which may contribute to the 
pathogenesis of multiorgan failure and poor outcome. 
As we used SOFA subscores to assess organ dysfunc- 
tion/failure, hematologic failure in our study refers to 
thrombocytopenia. In a prospective cohort of 329 critically 
ill patients, Vanderschueren and colleagues [22] found 
that thrombocytopenia was a risk marker for mortality, 
independent of and complementary to established severity 
of disease indices, and that both a low nadir platelet count 
and a large decrease in platelet count predicted a poor 
outcome in these patients. 

Several studies have reported risk factors associated 
with poor outcome in patients with ESRD in various 
settings, including age [5,7,23], higher severity scores 



Apel ef al. Critical Care 2013, 17:R298 
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Page 7 of 8 



[5-7], associated malignancy [5], the presence of infection 
[5-7,24], the need for mechanical ventilation [5,8], and 
anemia [25,26]. Data on risk factors for death in ESRD 
patients undergoing major surgical procedures are scanty. 
But this information may be important in risk stratifi- 
cation of patients prior to major surgical procedures. 
Previous studies have reported that the extent of organ 
dysfunction failure is associated with the risk of death in 
ICU patients with ESRD [5,7]. In our study, we identified 
hepatic SOFA subscores as being independently associated 
with an increased risk of in-hospital death. The use of 
central venous catheters for dialysis was also independ- 
ently associated with an increased risk of in-hospital 
death. This observation confirms the results of a Can- 
adian cohort of 578 ICU patients with ESRD [6]. This 
association may have been subject to a bias-by-indication 
in which sicker patients may have been preferentially 
dialyzed using central venous access in the ICU; never- 
theless, central venous catheters may be associated with 
additional risks related to catheter placement and risk 
of infection in the ICU, which may explain, at least in 
part, the possible association of central venous access 
and mortality in these patients. 

In agreement with the results of a previous study by 
Shah and colleagues [23], we found that female sex was 
associated with a more favorable outcome in patients with 
ESRD than male sex. Sexual dimorphism in the immune 
response has been correlated to differences in sex steroid 
hormone concentrations [27-29]. These differences in 
hormonal secretion may explain the improved survival of 
critically ill women. We also found that residual urinary 
output of greater than 500 mL was associated with a 
decreased risk of in-hospital death in patients with ESRD. 
This observation may be explained by the ability of kidney 
in these patients to reduce volume overload, which is 
known to be associated with deleterious effects on out- 
come of renal failure in the ICU [30]. 

Our study has some limitations. First, our analysis 
is retrospective in nature and our results are only 
hypothesis-generating. A larger prospective observational 
trial in surgical ICU patients or in specific subpopulations 
is warranted to clarify this issue. Second, the multivariable 
analysis does not take into account unmeasured variables 
and cannot establish a cause-effect relation. The confound- 
ing effect of unmeasured variables, such as perioperative 
volume management, cannot be excluded. Nevertheless, 
many relevant variables were considered in our analysis. 
Third, we included a heterogeneous case mix of surgical 
ICU patients and were not able to perform subgroup 
analysis for the different surgical disciplines, because of 
the relatively small number of patients with ERSD in 
the subgroups. Finally, the results of our study cannot 
be extrapolated to populations with other case mixes, 
such as medical patients. The singe-center nature of the 



study may be another limiting factor that hinders the 
extrapolation of data to other cohorts of surgical ICU 
patients with a different case mix. This should be explored 
in large-scale multicenter studies. Nonetheless, the absence 
of major variability in clinical practice in single-center 
studies, such as ours, may reduce the impact of the 
possible confounding effect of variability in ICU and 
hospital organizational issues that may be difficult to 
adjust for in large-scale multicenter studies. 

Conclusions 

In this single-center, large cohort of patients in the sur- 
gical ICU, ESRD was associated with higher morbidity 
and mortality. The presence of ESRD was independently 
associated with a higher risk of in-hospital death. Our data 
can be useful in preoperative risk stratification. Further 
large multicenter studies are warranted to confirm whether 
these data can be generalized to a wide range of patients 
in the surgical ICU. 

Key messages 

• Postoperative patients with end-stage renal disease 
(ESRD) have a high incidence of comorbidities and a 
high degree of severity of illness on admission to the 
intensive care unit (ICU). 

• These patients are more likely to have any type of 
organ failure during the ICU stay than those 
without ESRD, especially hematologic failure. 

• ESRD was independently associated with a greater 
risk of in-hospital death. 

• The use of central venous vascular access and higher 
hepatic Sequential Organ Failure Assessment 
(SOFA) subscores were independently associated 
with increased risk of in-hospital death, whereas 
female sex, admission after cardiac procedures, and 
residual urinary output of more than 500 mL versus 
anuria were independently associated with decreased 
risk of in-hospital death in patients with ESRD. 

Additional file 



Additional file 1: Table 51. The multivariable model used to obtain the 
propensity score. Table S2. Physiological, acid-base parameters, and 
serum electrolytes according to the presence of end-stage renal disease 
(ESRD). Table S3. Logistic regression analysis with hospital mortality as 
the dependent variable in the whole population. Table S4. Summary of a 
multivariable forvi/ard stepwise logistic regression analysis with in-hospital 
death as the dependent variable. 



Abbreviations 

CI: confidence interval; ESRD: end-stage renal disease; ICU: intensive care unit; 
LOS: length of stay; OR: odds ratio; SAPS II: Simplified Acute Physiology Score II; 
SOEA: Sequential Organ Eailure Assessment; SOEA^ax: maximum Sequential 
Organ Eailure Assessment score recorded during the intensive care unit stay. 



Apel ef al. Critical Care 201 3, 1 7:R298 Page 8 of 8 

http://ccforum.eom/content/17/6/R298 



Competing interests 

The authors declare that they do not have any competing interests in 
relation to the subject of this manuscript. 

Autliors' contributions 

MA contributed to the study design and helped collect data and revise 
the medical charts. YS contributed to the study design and helped perform 
the statistical analysis and draft the manuscript. KR and GW contributed to the 
study design and revised the manuscript. VPLM helped collect data, revise the 
medical charts, perform the statistical analysis, and draft the manuscript. CS 
helped collect data, revise the medical charts, and draft the manuscript. MZ 
helped collect data and revise the medical charts. All authors read and 
approved the final manuscript. 

Acl<nowledgments 

The authors are grateful to Karen Picket (Erasme Hospital, Free University of 
Brussels, Brussels, Belgium) for the editorial assistance and to Hassane Nigimi 
(Erasme Hospital) for the revision of the statistical analysis and the assistance 
in the multivariable analysis and propensity score matching. 

Autlior details 

'Department of Anesthesiology and Intensive Care, Friedrich-Schiller-University 
Hospital, Erianger Allee 103, 07743 Jena, Germany. ^Department of 
Anesthesiology and Intensive Care, Theodor Bilharz Institute, El-Nile St., Warrak 
El-Hadar, 1 241 1 Embaba, Giza, Egypt. ^Department of Internal Medicine III, 
Eriedrich-Schiller-University Hospital Erianger Allee 103, 07743 Jena, Germany. 

Received: 21 June 2013 Accepted: 26 November 2013 
Published: 23 December 2013 

References 

1. Kidney Disease Outcomes Quality Initiative: K/DOQI clinical practice 
guidelines for chronic kidney disease: evaluation, classification, and 
stratification. Arn J Kidney Dis 2002, 39:S1-S266. 

2. Lysaght MJ: Maintenance dialysis population dynamics: current trends 
and long-term implications. J Am Soc Nephrol 2002, 1 3:S37-S40. 

3. Meguid El Nahas A, Bello AK Chronic kidney disease: the global 
challenge. Lancet 2005, 365:331-340. 

4. National Institutes of Health, National Institute of Diabetes and Digestive 
and Kidney Diseases: Excerpts from the United States Renal Data Systems 
2002 annual report: Atlas of end-stage renal disease in the United States. 
Am J Kidney Dis 2003, 41:v-254. 

5. Strijack B, Mojica J, Sood M, Komenda P, Bueti J, Reslerova M, Roberts D, 
Rigatto C: Outcomes of chronic dialysis patients admitted to the 
intensive care unit. J Am Soc Nephml 2009, 20:2441 -2447. 

6. Sood MM, Miller L, Komenda P, Reslerova M, Bueti J, Santhianathan C, 
Roberts D, Mojica J, Rigatto C: Long-term outcomes of end-stage renal 
disease patients admitted to the ICU. Nepiirol Dial Transplant 201 1, 
26:2965-2970. 

7. Hutchison CA, Crowe AV, Stevens PE Harrison DA, Lipkin GW: Case mix, 
outcome and activity for patients admitted to intensive care units 
requiring chronic renal dialysis: a secondary analysis of the ICNARC Case 
Mix Programme Database. Crit Care 2007, 1 1:R50. 

8. Manhes G, Heng AE, Aublet-Cuvelier B, Gazuy N, Deteix P, Souweine B: 
Clinical features and outcome of chronic dialysis patients admitted to an 
intensive care unit. Nephrol Dial Transplant 2005, 20:1 127-1 133. 

9. Gall L Jr, Lemeshow S, Saulnier F: A new Simplified Acute Physiology 
Score (SAPS II) based on a European/North American multicenter study. 
JAMA 1993, 270:2957-2963. 

10. Vincent JL, Moreno R, Takala J, Willatts S, de Mendonca A, Bruining H, 
Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure 
Assessment) score to describe organ dysfunction/failure. On behalf of 
the Working Group on Sepsis-Related Problems of the European Society 
of Intensive Care Medicine. Intensive Care Med 1 996, 22:707-71 0. 

11. Hrstic I, Ostojic R: Chronic liver diseases in patients with chronic kidney 
disease. Acta Med Croatica 201 1, 65:349-353. 

1 2. USRDS: the United States Renal Data System. Am J Kidney Dis 2003, 42:1-230. 

13. The Renal Association, UK Renal Registry: The Sixth Annual Report http:// 
www.renalreg.com/Reports/2003.html. 

14. Arulkumaran N, Montero RM, Singer M: Management of the dialysis 
patient in general intensive care. Br J Anaesth 2012, 108:183-192. 



15. Kanbay M, Afsar B, Goldsmith D, Covic A: Sudden death in hemodialysis: 
an update. Blood Purif 20]0, 30:135-145. 

16. Kaw D, Malhotra D: Platelet dysfunction and end-stage renal disease. 
Semin Dial 2006, 19:317-322. 

17. Darlington A, Ferreiro JL, Ueno M, Suzuki Y, Desai B, Capranzano P, 
Capodanno D, Tello-Montoliu A, BassTA, Nahman NS, Angiolillo DJ: 
Haemostatic profiles assessed by thromboelastography in patients with 
end-stage renal disease. Thromb Haemost 201 1, 106:67-74. 

18. Chapman RJ, Templeton M, Ashworth S, Broomhead R, McLean A, Brett SJ: 
Long-term survival of chronic dialysis patients following survival from an 
episode of multiple-organ failure. CrIt Care 2009, 13:R65. 

19. Senthuran S, Bandeshe H, Ranganathan D, Boots R: Outcomes for dialysis 
patients with end-stage renal failure admitted to an intensive care unit 
or high dependency unit. Med J Aust 2008, 188:292-295. 

20. Uchino S, Morimatsu H, Bellomo R, Silvester W, Cole L: End-stage renal failure 
patients requiring renal replacement therapy in the intensive care unit: 
incidence, clinical features, and outcome. Blood Purif 2003, 21:170-175. 

21 . Sood MM, Roberts D, Komenda P, Bueti J, Reslerova M, Mojica J, Rigatto C: 
End-stage renal disease status and critical illness in the elderly. Clin J Am 
Soc Nephrol 2011,6:613-619. 

22. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, 
Wilmer A, Bobbaers H: Thrombocytopenia and prognosis in intensive 
care. CrIt Care Med 2000, 28:1 871 -1 876. 

23. Shah DS, Polkinghorne KR, Pellicano R, Kerr PG: Are traditional risk factors 
valid for assessing cardiovascular risk in end-stage renal failure patients? 
Nephrology (Carlton) 2008, 13:667-671. 

24. Sarnak MJ, Jaber BL Mortality caused by sepsis in patients with end-stage 
renal disease compared with the general population. Kidney Int 2000, 
58:1758-1764 

25. Saha M, Faroque MO, Alam KS, Alam MM, Ahmed S: Chronic kidney disease 
specific cardiovascular risk factors among non dialytic patients with chronic 
kidney disease stage-V-an experience of a specialized hospital. 
Bangladesh Med Res Counc Bull 201 2, 38:1 8-22. 

26. Kessler M: Cardiovascular disease in terminal end-stage renal failure- 
epidemiological aspects. Nephrologle 2002, 23:361-365. 

27. Combes A, Luyt CE Trouillet JL, Nieszkowska A, Chastre J: Gender impact on 
the outcomes of critically ill patients with nosocomial infections. Cnf Care 
Med 2009 37:2506-2511. 

28. Angstwurm MW, Gaertner R, Schopohl J: Outcome in elderly patients with 
severe infection is influenced by sex hormones but not gender. CrIt Care 
Med 2005, 33:2786-2793. 

29. Sperry JL, Nathens AB Frankel HL, Vanek SL, Moore EE Maier RV, Minei JP: 
Characterization of the gender dimorphism after injury and hemorrhagic 
shock: are hormonal differences responsible? Crif Care Med 2008, 
36:1838-1845. 

30. Payen D, de Pont AC, Sakr Y Spies C, Reinhart K, Vincent JL A positive fluid 
balance is associated with a worse outcome in patients with acute renal 
failure. Crif Core 2008, 12:R74 



doi:10.1186/cc13167 

Cite this article as: Apel et al:. End-stage renal disease and outcome in a 
surgical intensive care unit. Critical Care 2013 17:R298. 



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