Prediction of Poor Outcome Using the Urea to Albumin Ratio in Thoracic Empyema

Purpose The prognostic performance of urea-to-albumin ratio (UAR) has been assessed in various pulmonary and nonpulmonary conditions, but never in thoracic empyema. Therefore, our aim was to determine whether this marker has the ability to predict outcome in such patients. Methods A single-center retrospective study was conducted in a Clinic of Thoracic Surgery at a University Hospital between January 2021 and October 2023. A total of 84 patients who underwent emergency surgery due to thoracic empyema were involved. Serum levels of urea and albumin at admission were used to calculate UAR. We analyzed area under receiver operating characteristics (AUROC) curves of UAR, systemic inflammatory response syndrome (SIRS) and quick-sequential organ failure assessment (qSOFA), and compared their prognostic performance. Results The identified in-hospital mortality was 10.7%. The UAR showed the best ability to prognosticate mortality compared to qSOFA (AUROC = 0.828 vs 0.747) and SIRS (AUROC = 0.828 vs 0.676). We established a sensitivity of 87.5% and specificity of 74.2% at optimal cut-off value UAR > 51.1 for prediction of adverse outcome. Conclusion In patients with thoracic empyema urea-to-albumin ratio showed significant prognostic performance and a potential for clinical application as a low cost and widely available predictor of death.


Introduction
Thoracic empyema represents a life-threatening disease in both adults and children, requiring urgent diagnostic and treatment measures.Between 20% and 30% of patients either die or require additional surgical intervention in the first year after developing empyema [1].Developments in the management in recent decades have not led to the desired survival rates and empyema is still associated with high morbidity and mortality [2], making early diagnosis and prognosis crucial for final outcome.Prediction of lethal outcome using routine laboratory markers is a rapid and inexpensive way to evaluate high-risk patients, enabling timely adjustment of treatment strategy.
Serum albumin and urea are easily assessable and low cost biomarkers, which are used widely as diagnostic and prognostic tools in everyday practice.It is thought that urea levels in peripheral blood can reliably reflect the association between renal status, nutritional status and metabolism [3,4].Higher urea levels have been found to be a predictor of death in patients with thoracic empyema [2,5], critical illness [6] and sepsis [7].Lower serum albumin concentrations represent an unfavorable prognostic factor, which is common in critically ill patients, especially in those with infections and sepsis, and is strongly associated with adverse outcome [8].Hypoalbuminemia is a major cause of disorders in nutrient absorption, immune response, and production of plasma proteins [9].Hypoalbuminemia also significantly affects the pharmacokinetics and pharmacodynamics of anti-infective therapy, which further complicates the disease severity [8].Various studies have reported an association between lower albumin levels and mortality in patients with thoracic empyema [5,10,11], pneumonia [12], lung cancer [13], and sepsis [14,15].
The serum urea to albumin ratio (UAR), which represents an indirect indicator of the degree of dehydration, nutritional status and functional reserves of the liver and kidneys [16], has recently been found to be a significant predictor of death in pneumonia [17], critical illness [18,19], sepsis [20][21][22] and septic shock [23].However, the ability of UAR to prognosticate outcome in thoracic empyema has not yet been evaluated.Therefore, we aimed to find an association between UAR and mortality in such clinical setting.

Material and methods
This retrospective study was performed in a Clinic of Thoracic Surgery at a University Hospital on eighty-four patients with thoracic empyema over a 34-month period (January 2021 to November 2023).We reviewed the medical records of all adult patients with empyema thoracis who underwent emergency surgery.The diagnosis was determined by presence of pus or positive culture in pleural space [1].Our exclusion criteria were age < 18 years and use of immunosuppressants, however, no patient met them and finally 84 participants were involved in the analysis.
Demographic, laboratory and clinical data were obtained from electronic medical records of each patient on admission to the clinic.The primary endpoint of the study was to evaluate the significance of UAR in predicting of fatal outcome, whereat in-hospital mortality was considered.
A presence of systemic inflammatory response syndrome (SIRS) was defined as two or more of the following four signs: a heart rate > 90/minute, a respiratory rate > 20/minute, a body temperature < 36°C or > 38°C and a white blood cell (WBC) count < 4x10 9 /L or > 12x10 9 /L [24].A positive quick-sequential organ failure assessment (qSOFA) score was identified as ≥ 2 of the following 3 criteria: a systolic blood pressure ≤ 100 mmHg, a respiratory rate ≥ 22/minute and a Glasgow Coma Scale < 15 points [25].
The UAR was calculated by the equation: urea (mg/dL)/albumin (mg/dL) x 1000 [18] based on laboratory results at admission.Serum levels of urea and albumin were analyzed using a spectrophotometric method (AU480 Chemistry Analyzer, Beckman Coulter) in the hospital laboratory.
In all 84 patients WBC, SIRS and qSOFA were determined, while due to missing data in medical records we recorded serum C-reactive protein (CRP) and urea (Ur) in 81 patients, total protein (TP) in 75 patients, albumin (Alb) and UAR in 74 patients.SPSS Statistics 19.0 (IBM, Chicago, Illinois, USA) was used for data analysis.Prognostic values of UAR, SIRS and qSOFA were compared performing area under receiver operating characteristics (AUROC) curves.Continuous variables were expressed as mean (±SD) or median (IQR) for normally or nonnormally distributed data, respectively.Categorical variables were presented as frequency (%) and compared by Fisher exact test or Chi-square test.A p-value was considered significant at < 0.05.

Basic characteristics
Of the total of 84 patients, nine (10.7%) had a lethal outcome.Despite the observation that all patients who died were male, no significance was established for this variable according to outcome (p = 0.194).No significant differences between survivors (S) and nonsurvivors (NS) were established also for age (p = 0.186), hospital stay (p = 0.302), blood type (p = 0.092), comorbidity (p = 1.00), stage (p = 0.217) and location of empyema (p = 0.298).In contrast, patients who underwent minimally invasive surgery were found to have a higher chance of favorable outcome (p = 0.031) [Table 1].

Laboratory parameters and prognostic scores
Laboratory parameters WBC (p = 0.452), CRP (p = 0.663), TP (p = 0.556) and Alb (p = 0.506) failed to discriminate patients who died from those who survived.In contrast, levels of serum urea were higher in NS (10.1 vs 5.85, p = 0.002).More than half of participants had clinical evidence of SIRS (52.4%), however no significance according to outcome was observed (NS = 77.8%vs S = 49.3%, p = 0.16).NS had higher median qSOFA score (1 vs 0, p = 0.003) and a positive qSOFA was found more frequent in these patients (NS = 44.4% vs S = 8%, p = 0.01).We found UAR as a significant unfavorable indicator, with median values approximately twice as high in patients with poor outcome (NS = 60.54 vs S = 35.34,p = 0.003) [Table 2].

Logistic regression
The ability of UAR to predict mortality was analyzed by direct logistic regression [Table 4].The model using only the UAR was significant (p = 0.019), whereat the odds of adverse outcome increased by 1.019 by an increase on 1 point of the score.

Discussion
Thoracic empyema affects over 65,000 patients annually in the United States and the United Kingdom [5] and is associated with significant healthcare costs and a major workload on hospital staff [26].Approximately 1/4 of patients require prolonged hospitalization (more than 30 days) and between 10% and 20% of them had a poor outcome [27,28].Despite the advances in management of empyema thoracis in recent decades, mortality rates remain unsatisfactory high.An early prognostic evaluation can provide an objective classification of the infection severity and differentiate high-risk patients in whom more aggressive therapeutic measures can be applied.Unfortunately, most patients with empyema do not seek help in time and are hospitalized with a significant delay, which further complicates effective treatment.Finding accurate predictive biomarkers that could contribute to early prognosis and early assessment of treatment regimen remains a matter of great importance.
On a global scale serum albumin and serum urea are among the most common laboratory parameters routinely used to evaluate nutritional balance and disease severity.
Higher serum urea was strongly associated with mortality in patients with thoracic empyema according to Rahman et al. [5] (p < 0.001) and Tsai et al. [2] (p = 0.049).In the present study, we confirmed these findings by observing that higher urea concentrations correlated with lethal outcome (p = 0.002).Conversely, Marks et al. [10] in thoracic empyema reported lack of prognostic significance (p = 0.055).
Hypoalbuminemia was also found as unfavorable factor in patients with thoracic empyema.Marks et al. [10] and Chu et al. [11] observed that patients who died had significantly lower albumin concentration (NS = 27 vs S = 32 g/L, p = 0.014 and NS = 25.1 vs S = 27.8,p = 0.035, respectively).Developing a prognostic score for thoracic empyema, Rahman et al. [5] reported that albumin levels > 27 mmol/L were indicative for increased chance of survival (p < 0.001).In contrast, we failed to establish an ability of serum albumin to differentiate patients at high risk of death (p = 0.506).
Determining the criteria with the greatest impact on the final outcome to be included in reliable prognostic score is not an easy task.A number of factors have already been proven to correlate with mortality in patients with empyema -advanced age, comorbidity, immunosuppression, prolonged hospital stay, sepsis, septic shock, multiple organ failure, poor control of the source of infection, nosocomial etiology [5,10,29].A large number of researchers are still trying to deal with these problems, focusing on the prognostic capabilities of various scoring systems.However, most of the scores are complex and difficult for calculation, require multiple laboratory and clinical parameters, and are rarely used outside the intensive care units.This is not the case with simple laboratory prognostic indices or ratios, which are easily accessible and quickly calculated, requiring only 2 or 3 routine laboratory parameters.One of those ratios, the UAR has already shown promising predictive performance in various clinical settings [17][18][19][20][21][22][23], however it has never been investigated in thoracic empyema.

Table 1 .
Basic characteristics

Table 2 .
Laboratory parameters and prognostic scores

Table 4 .
Direct logistic regression model for predicting lethal outcome