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NDT Advance Access published online on January 10, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm914
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure

Ji-Tseng Fang1, Ming-Hung Tsai2, Ya-Chung Tian1, Chang-Chyi Jenq1, Chan-Yu Lin1, Yung-Chang Chen1, Jau-Min Lien2, Pan-Chi Chen2 and Chih-Wei Yang1

1 Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan 2 Division of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

Correspondence and offprint requests to: Yung-Chang Chen, Division of Critical Care Nephrology, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei, 105 Taiwan. Tel: +886-3-3281200 ext 8181; Fax: +886-3-3282173; E-mail: cyc2356{at}adm.cgmh.org.tw



   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 Reference
 
Background. End-stage liver disease is often complicated by renal function disturbances. Cirrhotic patients with acute renal failure admitted to intensive care units (ICUs) have high mortality rates. This work seeks to identify specific predictors of hospital mortality in critically ill cirrhotic patients with acute renal failure.

Methods. A total of 111 patients with cirrhosis and acute renal failure were admitted to ICU from March 2003 to February 2005. Twenty-six demographic, clinical and laboratory variables were prospectively gathered as predictors of survival on the first day of ICU admission.

Results. The overall hospital mortality rate was 81.1%. The univariate analysis identified 11 of the 32 variables as prognostically valuable. The multiple logistic regression analysis (excluding five scoring systems) indicates that the mean arterial pressure (MAP), serum bilirubin, respiratory failure and sepsis on the first day in ICU are significantly related to prognosis. The best Youden index (sensitivity + specificity – 1) yields cutoff points of 80 MAP (in mmHg) and 80 serum bilirubin (in µmol/L) (or 4.7 mg/dL) and indicates acute respiratory failure and sepsis. A simple model for mortality is developed on the basis of these four readily available parameters on Day 1 of ICU admission. The new score (MBRS score: MAP + bilirubin + respiratory failure + sepsis) displays an excellent area under the receiver operating characteristic curve (0.898 ± 0.031, P < 0.001). The mortality rate exceeds 90% when the MBRS (MAP + bilirubin + respiratory failure + sepsis) score is 2 or higher.

Conclusion. The MBRS score is a straightforward, reproducible and easily adopted evaluative tool with good prognostic abilities, which generates objective data for patient families and physicians and supplements a clinical judgment of prognosis.

Keywords: acute kidney injury; APACHE; Child—Pugh; ICU; prognosis



   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
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The prognosis of cirrhotic patients admitted to the intensive care unit (ICU) has been graved [1–3]. Multiple organ failure or dysfunction typically entails a very poor outcome in all ICU patients [4], and particularly in critically ill cirrhotic patients who develop an extrahepatic organ system failure or dysfunction [5,6]. Among the extrahepatic organ system failures often encountered in end-stage liver disease, renal failure or dysfunction in cirrhotic patients has been the subject of extensive investigation because of the functional nature, at least in part, and the capability of predicting morbidity and mortality [7,8].

Interest has recently been renewed in critically ill cirrhotics owing to the increasing application of sophisticated technology and medical care, such as terlipressin in hepatorenal syndrome and gastrointestinal bleeding, transjugular intrahepatic portosystemic shunt placement in uncontrolled gastrointestinal bleeding, molecular adsorbent re-circulating system and bioartificial livers in liver failure. Additionally, liver transplantation can provide long-term survival. These novel therapeutic possibilities need reliable prognostic factors to build valuable techniques for critically ill cirrhotics. Conversely, the circumstances in which ICU therapy may be futile should be assessed [9–14]. Mortality rates of cirrhotic patients with acute renal failure admitted to ICU are extremely high (>80%) [15,16]. In view of the promising new treatment and restricted medical resources, investigators and physicians require a reliable tool to risk-stratify and monitor the patients during practice and clinical trials.

This investigation has the following three goals: (a) to explore short-term mortality predictors in critically ill cirrhotic patients with acute renal failure; (b) to develop and validate a clinical new score that accurately predicts hospital mortality by accounting for the effect of all of its major risk factors and (c) to compare whether this new score performs better with liver-disease-specific scores [Child–Pugh points [17] and model for end-stage liver disease (MELD) [18]] and general ICU prognostic models [sequential organ failure assessment (SOFA) [19] and acute physiology, age, chronic health evaluation II and III (APACHE II & III) [20,21]] in this homogenous group in an ICU admission setting.



   Methods
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 Introduction
 Methods
Results
 Discussion
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Patient information and data collection
The local ethics committee approved the study protocol. Formal consent was obtained from each patient's next of kin. This study was undertaken in a 10-bed specialized hepatogastroenterology ICU at a 2000-bed university hospital in Taiwan, between March 2003 and February 2005. In total, 111 consecutive patients with hepatic cirrhosis and acute renal failure requiring intensive monitoring and/or treatment that could not be provided outside the ICU were enrolled. Only those cirrhotic patients with acute renal failure were included. Exclusion criteria were as follows: patients who did not match the criteria of acute renal failure (see later) (50 patients); previous end-stage renal disease (chronic uraemic) patients undergoing regular renal replacement therapy (22 patients); the length of hospital stay <24 h (25 patients) and/or patients who had received liver transplantation (8 patients). Readmitted patients were also excluded from the study (12 patients).

Prospectively collected data were as follows: demographics; reason for ICU admission; acute diagnosis; illness severity; MELD, SOFA, APACHE II and III on the first day of ICU admission; the length of hospitalization and outcome. The primary study outcome was the hospital mortality rate. Follow-up at 6 months after hospital discharge was performed in telephone interviews. The registry office provided information regarding patient survival or the date of death when necessary.

Definitions
The diagnosis of cirrhosis was based on liver histology or a combination of physical signs and biochemical and ultrasonographic findings. Acute renal failure was defined as a serum creatinine (SCr) level over 1.5 mg/dL (132.6 µmol/L) or a 50% rise in serum creatinine, after correcting for prerenal causes and mechanical obstruction, or an acute requirement for renal replacement therapy. Serum creatinine measurement was repeated following diuretic withdrawal in patients receiving diuretics. A cutoff value of 1.5 mg/dL of SCr was applied, since previous investigations have shown that patients with cirrhosis with a creatinine level >1.5 mg/dL have a significantly decreased glomerular filtration rate [22], and this is also the cutoff level used to define hepatorenal syndrome [23]. A rise of 50% in SCr for acute renal dysfunction cited the RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage renal failure) classification (RIFLE-R stage: SCr had risen by a factor of 1.5 or more from the baseline) [24–26]. Baseline SCr was the first value measured during hospitalization. The modification of diet in renal disease (MDRD) formula was applied for 12 patients to estimate baseline SCr concentrations as those patients admitted directly to the ICU and their previous SCr levels on admission were unknown [24]. Respiratory failure is defined as a respiratory rate of ≤5/min or ≥50/min and/or mechanical ventilation for ≥3 days and/or fraction of inspired oxygen (FiO2) >0.4 and/or positive end-expiratory pressure >5 cm H2O [4,5,9]. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference [27]. The severity of liver disease on ICU admission was graded by the Child–Pugh system and the MELD score. Illness severity also was assessed by the SOFA, APACHE II and III scoring systems. These scoring systems have been validated to predict the outcomes of critically ill patients with cirrhosis. The worst physiological and biochemical values during the first day of ICU admission were recorded.

Clinical management
In brief, patients with upper gastrointestinal bleeding caused by oesophageal varices (44 patients) were initially treated with emergency sclerotherapy associated with vasopressin derivatives administration. Patients with peptic ulcer (40 patients) either with active bleeding, visible vessel or clot were treated with the injection of sclerosing agents, followed by proton pump inhibitors. Intravenous fluids were administered to all patients depending on their volume status. PRBC were administered according to the criteria of the attending physician or whenever the haemoglobin decreased <8 g/dL. In all patients, the presence of bacterial infections (45 patients) at admission and their development during hospitalization was investigated with appropriate diagnostic methods and cultures. Patients were then started on appropriate empiric antibiotic therapy intravenously. To patients developing signs of acute renal failure (oliguria and/or increase in serum creatinine), blood volume expansion with PRBC, albumin and/or artificial plasma expanders (56 patients) was given to improve renal function and increase urine volume. If oliguria persisted after volume depletion had been corrected or excluded, vasoactive agents with or without the addition of a loop diuretic were prescribed [8]. When acute renal failure was severe or progressive and measures to improve renal function had been unsuccessful, renal replacement therapy was performed (11 patients).

Statistical analysis
Continuous variables were summarized by mean and standard derivation unless otherwise stated. The primary analysis compared hospital survivors with nonsurvivors. All variables were tested for normal distribution with the Kolmogorov–Smirnov test. The Student's t-test was employed to compare the means of continuous variables and normally distributed data; otherwise, the Mann–Whitney U test was employed. Categorical data were tested by the chi-square test. The analysis of variance (ANOVA) test with the Tukey–Kramer test post hoc for numerical values and the chi-square test for trends were applied to assess categorical data associated with new scores (see the Results section). Finally, risk factors were assessed using univariate analysis, and variables that were statistically significant (P < 0.05) in the univariate analysis were included in multivariate analysis by adopting a multiple logistic regression based on the forward elimination of data. We used three models for multivariate analysis. In model 1, we analysed those statistically significant variables in univariate analysis. In model 2, we included those statistically significant variables in univariate analysis except for all scoring systems (because each score comprises many parameters) [6]. Based on model 2, we identified independent prognostic factors to generate a simple new score (see the Results section) for in-hospital mortality. After the new score was designed, we examined all statistically significant variables in univariate analysis plus the new score in multivariate analysis model 3. The correlation of paired variables within groups was assessed using linear regression with a Pearson analysis.

Calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test (C statistic), which compares the number of observed and predicted deaths in risk groups for the entire range of probabilities of death. Discrimination was explored using the area under a receiver operating characteristic curve (AUROC). An AUROC close to 0.5 indicates that the model performance approximates that of flipping a coin. However, the model nears 100% sensitivity and specificity despite any cutoff point as the area nears 1.0. To compare the areas under the two resulting AUROC curves we used a nonparametric approach [28]. The sensitivity, specificity and overall correctness for the serum bilirubin level, with/without respiratory failure, with/without sepsis, mean arterial pressure (MAP), new score, Child–Pugh, MELD, APACHE II, III and SOFA scores were determined. Finally, cutoff points were calculated by obtaining the best Youden index (sensitivity + specificity – 1) [29].

Cumulative survival curves as a function of time were generated by the Kaplan–Meier approach and compared with the log-rank test. The Cox proportional hazards model was applied to determine the significance of variables for predicting 6-month mortality (the second end point). All statistical tests were two-tailed; a value of P < 0.05 was regarded as statistically significant. Data were analysed with SPSS 12.0 for Windows 95 (SPSS, Inc., Chicago, IL, USA).



   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 Reference
 
Subject characteristics
Between March 2003 and February 2005, 111 cirrhotic patients with acute renal failure were enrolled at the specialized hepatogastroenterology ICU. The patient median age was 56 years; 81 patients were male (73%) and 30 were female (27%). The overall in-hospital mortality rate for the whole group was 81.1% (90/111). Table 1 shows the patient demographic data and clinical characteristics of survivors and non-survivors. Table 2 describes the cause of cirrhosis, the reasons for ICU admission and the presumptive aetiology of acute renal failure. Liver diseases were usually attributed to hepatitis B viral infection. The most frequent reason for ICU admission was upper gastrointestinal bleeding. Meanwhile, patients who developed acute renal failure tended to have a history of infection (45/111, 41%). Only 14% of ICU cirrhotics with acute renal failure were classified as hepatorenal syndrome, and none of these patients survived (see the Discussion section).


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  		Table 1 Patients’ demographic data and clinical characteristics

 

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  		Table 2 Causes of cirrhosis, reasons for ICU admission and presumptive causes of acute renal failure

 
Risk factors for hospital mortality
Univariate analysis identified 11 of the 32 variables as prognostically valuable (Table 3). Multivariate analysis identified the following variables as having independent prognostic significance: MAP, sepsis, APACHE III and MELD (Model 1: including all 11 parameters), and MAP, serum bilirubin, respiratory failure and sepsis on the ICU first day (Model 2: excluding all five scoring systems). Only the new score (see below) and APACHE III reached prognostic significance for in-hospital mortality in Model 3 (accompanied by 11 parameters in Model 1 plus the new score). The regression coefficients of Model 2 variables were adopted to calculate a logit of death for every patient as follows:


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  		Table 3 Variables showing prognostic significance

 
Log (odds of death) = 3.749 – 0.061 x MAP (in mmHg) + 0.007 x serum bilirubin (in µmol/L) + 2.069 x respiratory failure (with = 1/without = 0) + 2.090 x sepsis (with = 1/without = 0).

Indices for predicting short-term prognosis and the new score (MBRS score) developed
The validity of each scoring system for the sensitivity, specificity and overall correctness of prediction was obtained to determine their ability to predict hospital mortality. Table 4 presents these data calculated by the cutoff point providing the best Youden index. A simple model for mortality, based on the best Youden index for the multivariate analysis, that identified four independent prognostic predictors of lower thresholds of 80 MAP (in mmHg) (one point) (including 31 patients out of 79 therapy with vasoactive medication), upper thresholds cutoffs of 80 serum bilirubin (in µmol/L) (or 4.7 mg/dL) (one point), with acute respiratory failure (one point) and sepsis (one point) for Day 1 of ICU admission, was developed. In doing so, a new score (MBRS score, i.e. mean arterial pressure, bilirubin, respiratory failure and sepsis) was defined according to the sum of the values of the individual predictor, each ranging from 0 to 4. The MBRS score had the best Youden index and the highest overall correctness of prediction, as compared with the Child–Pugh points, MELD, APACHE II, III and SOFA scores (Table 4).


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  		Table 4 Prediction of subsequent hospital mortality on the first day of ICU admission

 
Hospital mortality and severity of illness scoring systems
Hospital mortality rates differed significantly according to the best Youden index below and above cutoffs of 80 MAP (in mmHg) (88.6% versus 62.5%, P = 0.003), 80 serum bilirubin (in µmol/L) (or 4.7 mg/dL) (63% versus 93.8%, P <0.001), with/without acute respiratory failure (92.3% versus 71.2%, P = 0.005) and sepsis (93.3% versus 66.7%, P = 0.006), 1 MBRS score point (41.9% versus 96.3%, P < 0.001), 10 Child–Pugh points (60% versus 87.2%, P = 0.007), 34 MELD points (69.5% versus 94.2%, P = 0.001), 25 APACHE II points (69.1% versus 92.9%, P = 0.003), 88 APACHE III points (46.2% versus 91.8%, P < 0.001) and 11 SOFA points (64.2% versus 96.6%, P < 0.001) (Table 4).

The data required to calculate the MBRS score on Day 1 of ICU admission were available for all 111 patients. Hospital mortality was 33.3% (2/6) for the MBRS score = 0, 44% (11/25) for the MBRS score = 1, 90.9% (30/33) for the MBRS score = 2 and 100% (47/47) for the MBRS score = 3 and 4 ({chi}2 for trend, P < 0.001) (Table 5). A progressive and significant elevation in mortality was correlated with the rising MBRS score among all patients. The odds ratios for the MBRS score were 1.571 (P = 0.636) for MBRS score = 1 versus MBRS score = 0, 20 (P = 0.005) for MBRS score = 2 versus MBRS score = 0 and infinity (P < 0.001) for MBRS score = 3 and 4 versus MBRS score = 0 (Table 5). Cumulative survival rates differed significantly (P < 0.05) for MBRS score = 0 versus MBRS score = 1, 2, 3 and 4, and MBRS score = 1 versus MBRS score = 2, 3 and 4 (Figure 1).


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  		Table 5 MBRS score for critically ill cirrhotic patients with acute renal failure

 

Figure 1
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  		Fig. 1 Cumulative survival in 111 critical ill cirrhotic patients with acute renal failure according to their MBRS score after the first day of admission to a specialized hepatogastroenterology intensive care unit.

 
Table 6 shows the goodness-of-fit, as measured by the Hosmer–Lemeshow chi-square statistics of predicted mortality risk, and the predictive accuracy of the MBRS score, Child–Pugh points, MELD, APACHE II, III and SOFA. Table 6 also lists the discrimination for the MBRS score, Child–Pugh points, MELD, APACHE II, III and SOFA scores. The MBRS score had better discriminatory power than Child–Pugh points, MELD, APACHE II, III and SOFA scores. The AUROC of the MBRS score was significantly better (P < 0.05) than that of the Child–Pugh and APACHE II scores (Table 6).


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  		Table 6 Calibration and discrimination for the scoring methods in predicting hospital mortality

 
At the end of the 6-month observation period, four scoring systems (MBRS, SOFA, APACHE III and MELD scores) had prognostic value according to the univariate (unadjusted) hazard analysis (Table 7). Cox multivariate regression analysis revealed that—after adjustment for all six scores—the presence of only the MBRS score was of prognostic significance for the 6-month mortality of patients (Table 7).


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  		Table 7 Cox regression analysis of the six scoring systems according to the first day of ICU admission for 6-month mortality

 


   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
Reference
 
The overall mortality rate in this investigation was 81.1%, which is consistent with previous reports revealing that cirrhotic patients with acute renal failure admitted to an ICU have an extremely poor prognosis [15,16]. This investigation discovered that MAP, serum bilirubin, respiratory failure and sepsis on the first day of ICU admission were prognostically significant variables for those patients (Table 3). This work proposed and internally validated predictive models for mortality and resource utilization in ICU patients with cirrhosis and acute renal failure. This study has indicated that the MBRS score is a good prognostic system for predicting in-hospital mortality in critically ill cirrhotic patients with acute renal failure and has also confirmed that the MBRS score had better discriminatory power than Child–Pugh points, MELD, APACHE II, III and SOFA scores. In particular, the MBRS score was significantly better (P < 0.05) than the Child–Pugh and APACHE II scores (Table 6). Mortality rates rose significantly with the rising MBRS score among all patients. This investigation found that for ICU cirrhotic patients with acute renal failure, these groups had significant odds ratios for hospital mortality with a stepwise rise (MBRS score = 1, 1.571; MBRS score = 2, 20 and MBRS score = 3 and 4, infinity versus MBRS score = 0) (Table 5). Mortality rates rose substantially when the MBRS scores of 2, 3 and 4 were included in the calculation (Figure 1). At the end of 6 months of follow-up, Cox multivariate regression analysis revealed that only the MBRS score reached prognostic significance after adjustment for all six scoring systems (Table 7). These results demonstrate that the MBRS score is a good measurement of the severity of disease in this homogeneous patient subset when obtained early, so that a prognosis can be made promptly in the clinical course. This classification technique is also simple, straightforward, inexpensive, easy to perform and reproducible, such that a score can be obtained away from where it was obtained. The MBRS score can help in predicting a prognosis for critically ill cirrhotic patients with acute renal failure and may also aid the decision-making process.

We developed a simple prognostic model comprising four variables (<80 mmHg of MAP, >80 µmol/L of serum bilirubin, acute respiratory failure and sepsis) to predict in-hospital mortality. The severity of hepatic disease, defined as high bilirubin (or the presence of jaundice), severe encephalopathy or high Child–Pugh score, was independently associated with mortality. This work applied the best Youden index and recognized a cutoff value of 80 µmol/L of serum bilirubin (Table 4). The hospital mortality rates below and above the cutoff value of 80 µmol/L (4.7 mg/dL) serum bilirubin were 63% (29/46) and 93.8% (61/65) (P < 0.001), respectively. Moreover, the predictive accuracy and discriminative power for Child–Pugh points in this study are comparable with those from previous reports [1,5]. The Child–Pugh score reveals the severity of underlying liver disease but is not the ideal tool for predicting mortality or resource usage in cirrhotic patients with multiple organ failure [3,5]. The lack of extrahepatic parameters in the Child–Pugh score and the lack of liver-specific prognostic factors in the APACHE II score may account for their significant inferiority to MBRS scores in discriminative capability (Table 6). Previous studies have shown the influence of haemodynamics and respiratory function, which are not measured in the Child–Pugh score, on the morbidity and mortality of liver cirrhotic patients with acute renal failure [1,3,9]. The MELD score has very good short-term (3-month) prediction for end-stage cirrhotics, but it requires computer computation [9]. However, multivariate analysis in model 2 showed that MAP, serum bilirubin, respiratory failure and sepsis were associated with in-hospital mortality, whereas the SCr level was not. Both its overall correctness and discrimination capability are inferior to those of the MBRS score. The MBRS score might reflect the significance of extrahepatic and extrarenal, e.g. sepsis, haemodynamic status, and respiratory failure, that are not measured in MELD scores. The APACHE III system has been designed to increase prediction accuracy for critically ill patients, using a continuous weighing scheme for physiological variables, age and comorbid conditions. However, the number and categorization of variables in the APACHE III score have increased. Enhancement in statistical power in turn increases the complexity. Nevertheless, APACHE III is still considered economical [3,15].

Recent research strongly indicates that cardiodepression during sepsis contributes to the pathogenesis of hepatorenal syndrome. Patients with cirrhosis and portal hypertension exhibit characteristic cardiovascular and pulmonary haemodynamic changes. A vasodilatatory state and a hyperdynamic circulation influencing the cardiac and pulmonary functions dominate the circulation. The hyperdynamic syndrome consists of the raised heart rate, cardiac output and plasma volume and a decreased systemic vascular resistance and arterial blood pressure [30–36]. Analytical results demonstrate that MAP is an independent risk factor for critically ill cirrhotic patients with acute renal failure. Glomerular blood flow is autoregulated by the pre-glomerular arteriole until the MAP decreases to 80 mmHg. The flow falls below this pressure. Autoregulation is achieved by arteriolar dilatation (partly mediated by prostaglandins and partly myogenic) as pressure falls and by vasoconstriction when pressure rises. Glomerular filtration pressure is further maintained by the constriction of post-glomerular arterioles mediated by angiotensin II when the perfusion pressure continues to decline [37]. Notably, this work adopted the best Youden index and established a cutoff value of 80 mmHg of MAP (Table 4). Hospital mortality rates differed significantly (P = 0.003) below and above cutoffs of 80 MAP (in mmHg) in this investigation.

Cirrhosis is linked with increased relative risk and death from acute respiratory failure. Additionally, cirrhotic patients needing mechanical ventilation have an extremely poor prognosis [38]. Some studies have found that respiratory failure was not a significant prognostic factor probably because they did not distinguish between hypoxaemia needing ventilatory support and elective intubation, especially in cirrhotics with bleeding or encephalopathy [1,5,9]. In this investigation, the incidence and hospital mortality rates for cirrhotic patients with acute renal failure and acute respiratory failure were 46.8% (52/111) and 92.3% (48/52), respectively (Table 1). Patients with cirrhosis have a compromised lung function with a decreased transfer factor and ventilation/perfusion abnormalities, and arterial hypoxaemias were seen in 30–70% of patients with chronic liver disease, according to the severity. Various pathophysiological factors, such as an abnormal ventilation/perfusion ratio, the presence of arterial venous shunts and changes in the alveolar-arterial membrane, may be involved in the reduced diffusing capacity [39].

Sepsis is a frequent cause of acute renal failure and is associated with a worse prognosis than other causes. Patients with cirrhosis are susceptible to bacterial infection [2], which can lead to circulatory dysfunction, renal failure, hepatic encephalopathy and decreased survival. The development of renal failure in patients with cirrhosis and sepsis was associated with a marked impairment of survival, even in patients in whom renal failure was reversible [40]. The mortality of our critically ill cirrhotic patients who developed renal failure without sepsis was 66.7% during hospitalization and increased to 93.3% for those patients with renal failure and sepsis (P = 0.006). Patients with cirrhosis are characterized by hyperdynamic circulation, which is closely related to the complications of cirrhosis. The haemodynamic impairment can be made worse during sepsis, leading to multiple organ failure and mortality [2,30–36,40].

The specific prognostic score for cirrhotic patients with acute renal failure admitted to ICU derived in this study needs validation in further cohort studies. Further confirmation is particularly important as decreasing mortality was observed over time despite the similar patient characteristics at the time of ICU admission. Possible causes that may not have affected scoring variables, including improved therapies and the management of bleeding, renal failure, respiratory failure and sepsis, require additional testing in new cohorts [9,41,42]. The MBRS score was tested in the same way using data collected from April 2001 to March 2002 [15] that were not included in the original analysis or generation of the model. The MBRS score still had better discriminatory power (AUROC = 0.904 ± 0.047) than Child–Pugh points (AUROC = 0.772 ± 0.094), MELD (AUROC = 0.802 ± 0.064), APACHE II (AUROC = 0.797 ± 0.068), III (AUROC = 0.878 ± 0.050) and SOFA (AUROC = 0.868 ± 0.051) scores.

National Health Insurance in Taiwan did not provide coverage for terlipressin plus albumin in hepatorenal syndrome until the middle of 2005. The lack of treatment with terlipressin plus albumin at least partly explains the fatal outcomes in the 16 hepatorenal syndrome patients. Of all the cirrhosis complications, hepatorenal syndrome has the worst prognosis. Because of the lack of specific diagnostic tests, hepatorenal syndrome should only be diagnosed after excluding other disorders associated with renal failure in cirrhosis. Differentiating between hepatorenal syndrome and acute tubular necrosis is particularly difficult. Acute tubular necrosis in cirrhosis should be suspected when renal failure develops in a setting of hypovolaemic or septic shock or when administering nephrotoxic agents. Therefore, the presence of these conditions immediately before renal failure develops is currently deemed sufficient to diagnose acute tubular necrosis and to exclude hepatorenal syndrome [23]. The incidence of hepatorenal syndrome in this study was ~14% (Table 2). This finding is higher than that of another current prospective study of renal failure in patients with cirrhosis, which so far includes 142 episodes of renal failure diagnosed over 1 year. Thus far, the frequencies of the different causes of renal failure observed in that study are 32% infection-induced renal failure, 24% parenchymal renal diseases, 22% prerenal failure, 11% acute tubular necrosis, 8% hepatorenal syndrome and 3% nephrotoxic renal failure [7].

Despite the encouraging results, this study has several limitations. First, the MBRS scoring system was developed specifically for critically ill patients with cirrhosis and acute renal failure. Second, this study was conducted at just one institution; consequently, the results may not be directly extrapolated to other patient populations. Third, the patient population contained a high proportion of hepatitis B (55%) patients (Table 2) and hepatoma (35.1%) patients (Table 1), meaning that this study's applicability to typical North American and European patients with hepatitis C or who are alcoholics may be limited. Fourth, the sequential measurement of these scoring systems (e.g. daily, weekly) may reflect the dynamic aspects of clinical diseases, thus providing superior information on mortality risk. Finally, the prognostic instruments were tested on patients already admitted to intensive care, rather than being used as a preadmission screening tool, which also may have skewed the measured results.

In conclusion, this study shows that the prognosis for cirrhotic patients with acute renal failure admitted to ICU is very poor. This investigation also determines the predictors of MAP, serum bilirubin, acute respiratory failure and sepsis that are independently associated with hospital mortality. Analytical data also demonstrate the good discriminative power of the MBRS score in predicting the hospital mortality of critically ill cirrhotics with acute renal failure. Considering the economy and ease of implementation, we conclude that the MBRS score can raise the accuracy of the short-term prognosis in this homogeneous subset of patients.



   Acknowledgments
 
This work was supported by the Chang Gung Medical Research Fund CMRPG-32064, Chang Gung Memorial Hospital, Linkou, Taiwan and in part by National Science Council of Taiwan (NSC 95-2314-B-182A-190).

Conflict of interest statement. None declared.



   Reference
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Reference
 

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Received for publication: 12. 6.07
Accepted in revised form: 3.12.07


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