Relationship between blood urea nitrogen to serum albumin ratio and short-term mortality among patients from the surgical intensive care unit: a population-based real-world study

With the continuous progress of medicine and the construction of subspecialization, the surgical intensive care unit (SICU) has provided better protection for the treatment and care of surgical perioperative patients, especially for critically ill surgical patients, and thus has significantly reduced the mortality rate of patients [1‐3]. Nevertheless, the number of patients admitted to SICU continues to increase, accounting for nearly one-third of ICU patients, and the mortality rate of SICU patients remains high, even up to 50% in some less developed countries [4‐6]. Therefore, identifying high-risk factors for death in SICU patients are essential to reduce mortality.

Blood urea nitrogen (BUN) is a byproduct of protein breakdown within the human body and is primarily eliminated through renal excretion. Consequently, its concentration serves as a significant determinant of renal function, metabolic condition, and nutritional status [7]. A case–control investigation revealed that elevated BUN levels were associated with a heightened likelihood of postoperative stroke subsequent to cardiac surgery [8]. Additionally, serum albumin, a negative acute phase reactant, has demonstrated prognostic value in various critical ailments, indicating an unfavorable outcome [9, 10]. The blood urea nitrogen to serum albumin ratio (B/A) is a novel inflammation prognostic marker that is calculated from two simple indicators, including urea nitrogen and albumin. It has been reported that the B/A was an independent risk factor for the prognosis of patients with a variety of critical illnesses, including chronic heart failure [11], aspiration pneumonia [12], myocardial infarction [13], acute pulmonary embolism [14], sepsis [15], and gastrointestinal bleeding [16].

However, the aforementioned studies primarily concentrate on prognostic prediction in a singular critical illness, and there is a dearth of research investigating whether B/A also severs as a superior prognostic indicator for patients in the SICU. Consequently, this retrospective population-based study aims to examine the relationship between B/A and short-term outcomes (30-day and 90-day mortality) in patients admitted to SICU by gathering pertinent data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.

It is well-established that protein catabolism is heightened in critically ill patients, leading to an elevation in BUN levels. Renal reabsorption of urea nitrogen likewise affects the BUN levels of patients. Urea nitrogen is passively reabsorbed with water and sodium in the proximal renal tubule. In the more distal renal units, urea nitrogen reabsorption is also closely related to water reabsorption under the influence of antidiuretic hormone, which in turn is regulated by angiotensin II. When patients are dehydrated or have certain cardiovascular diseases occurring, sympathetic excitation and activation of the renin–angiotensin–aldosterone system can increase the reabsorption of urea nitrogen by the body. Therefore, high BUN level also reflects the state of renal hypoperfusion caused by hypovolemia or reduction of cardiac output [17]. One study has already reported that BUN levels at admission and at discharge were predictors of prognosis in patients with heart failure, and patients with high BUN levels had a poorer prognosis [18]. Additionally, serum albumin serves as a partial indicator of the organism's nutritional status and fulfills crucial functions such as maintaining plasma colloid osmolality, acting as an antioxidant, eliminating oxygen free radicals, serving as a carrier for various compounds, and inhibiting platelet activation and aggregation [19, 20]. Hypoalbuminemia has linked to decreased overall survival and increased recurrence rates in diverse malignant tumors [21, 22].

Notably, in recent studies, B/A has been employed as a novel prognostic predictor for critically ill patients. A study that included 800 hypertensive COVID-19 patients showed that urea nitrogen, albumin, and B/A were all valid predictors of in-hospital mortality, while B/A was a more reliable predictor than urea nitrogen and albumin [23]. Another study on the long-term prognosis of patients with acute myocardial infarction in the ICU found that a higher B/A (> 7.83) was associated with four-year mortality and was an independent risk factor for long-term mortality in such patients. In the ROC curve, the AUC value of B/A was higher than that of systemic inflammatory response syndrome (SIRS) score and APACHE II score [24]. In addition, there have been several studies showing that B/A has equally good predictive value in determining the prognosis of critically ill patients with certain surgical-related conditions. Allameh F et al. in their study analyzing the relationship between B/A and prognosis of patients with Fournier's Gangrene found that there was a significant difference between the B/A values of the death group and the survival group, and that elevated B/A was an independent predictor of death in patients with Fournier's Gangrene [25]. Ye L et al. collected data on 2527 cardiac surgery patients in the MIMIC database and analyzed factors associated with prognosis, and found a significant relationship between elevated B/A and hospital mortality. B/A might serve as an independent risk factor for adverse outcomes in patients undergoing cardiac surgery, and the investigators reached similar conclusions in an external validation cohort [26].

The present study, to the best of our knowledge, is the first to explore the association between B/A and the prognosis of patients admitted to the SICU. Our study found that patients in the death group were older and had higher SOFA scores, SAPS II scores, and higher proportions of mechanical ventilation. In this study, the enrolled patients were grouped by B/A quartiles and the differences in 30- and 90-day mortality rates were statistically significant among the four groups of patients. Kaplan–Meier analysis showed that the 30-day and 90-day cumulative survival rate gradually decreased as B/A increased, with patients in the highest quartile of B/A having the lowest survival rate. Cox regression analysis suggested that elevated B/A (> 9.69) was an independent risk factor for 90-day all-cause mortality in SICU patients. It is well known that albumin is produced by the liver, so when patients suffer from severe liver disease or cirrhosis, it can affect albumin levels [27, 28]. Therefore, this study conducted sensitivity analyses after excluding patients with severe liver disease or cirrhosis and those who had been infused with albumin within 48 h of admission to the hospital, and still ended up with the same conclusion.

The present clinical risk assessment of critically ill patients primarily relies on the utilization of APACHE II score, SOFA score, SAPS II score, and SIRS score [29, 30]. The prognostic predictive efficacy of these conventional scoring systems in the clinical management of critically ill patients is evident and has been validated in our study through the analysis of ROC curves. On this basis, researchers are actively engaged in the pursuit of novel and more straightforward prognostic markers. The analysis of ROC curves demonstrate that the AUC of the B/A ratio closely approximates the AUC of both the APACHE II score and SOFA score. Furthermore, when these three indices are combined, the AUC of the comprehensive index surpasses that of any individual index. This finding implies that B/A improves the prognostic predictive capacity of traditional scoring indicators, offering a novel viewpoint for clinicians and caregivers.

The current study has several advantages. First, the present study was innovative in exploring the correlation between B/A, a clinical indicator, and prognosis for SICU patients. Second, the study was more comprehensive in using 30-day and 90-day mortality to represent short-term prognosis. Finally, the sample size of this study was relatively large, and it is a large population-based real-world study.

However, this study still had some limitations. First, this study was a retrospective analysis with some bias. In addition, this study explored the correlation between B/A and short-term prognosis based on the initial value at the time of admission to the ICU, and did not further evaluate the correlation between B/A and long-term prognosis, and the dynamic changes of B/A levels. Finally, our analysis was limited to all-cause mortality and did not explore specific causes of death. Therefore, rigorously designed prospective studies are still needed to validate the findings of this study.

To summarize, elevated B/A level (> 9.69) on admission was an independent risk factor for increased short-term mortality in SICU patients, and had some potential application as a clinically simple, inexpensive and easily accessible biomarker.