Role of Presepsin as a Predictive Factor for Sepsis in Patients With Urinary Tract Infection Associated With Ureteral Calculi: A Retrospective Cohort Study
Article information
Abstract
Purpose
Recently, multiple studies have reported presepsin as a useful inflammatory biomarker for early sepsis diagnosis in patients with urinary tract infections (UTIs). Nonetheless, few studies have evaluated the efficacy of presepsin in urosepsis associated with ureteral calculi. We retrospectively investigated the efficacy of presepsin for early urosepsis diagnosis associated with ureteral calculi.
Materials and Methods
Between May 2021 and July 2023, 64 patients with UTI associated with ureteral calculi were included. Sepsis was defined as a Sequential Organ Failure Assessment (SOFA) score increase of ≥2 points. Patients were divided into 2 groups, with (n=38) and without (n=26) sepsis, and we assessed clinical characteristics (age, sex, and past medical history), laboratory data, and stone characteristics. Additionally, we evaluated predictive factors for urosepsis associated with ureteral calculi and compared these factors with inflammatory biomarkers.
Results
The proportion of females in the sepsis and nonsepsis groups was 89.5% (n=34) and 61.5% (n=16), respectively. In univariable analysis, low albumin level, low platelet count, and presepsin and procalcitonin (PCT) levels correlated with sepsis (p<0.05). In univariable logistic regression analysis, quick SOFA (odds ratio [OR], 2.071; p=0.033), C-reactive protein (CRP; OR, 1.08; p=0.01), PCT (OR, 1.025; p=0.008), and presepsin (OR, 1.354; p=0.001) were significantly associated with sepsis. In multivariate logistic regression analysis, presepsin (OR, 1.321; p=0.003) was significantly associated with sepsis. In receiver operating characteristic curve analysis of inflammatory markers, the areas under the curve for CRP, PCT, and presepsin were 0.704, 0.777, and 0.814, respectively.
Conclusions
Elevated presepsin levels may help predict sepsis occurrence in patients with UTI associated with ureteral calculi, thereby supporting timely and appropriate intervention.
HIGHLIGHTS
The presepsin is known as a useful inflammatory biomarker for early sepsis diagnosis. In this study, elevated presepsin level may help to predict sepsis occurrence in urinary tract infection associated with ureteral calculi, thereby facilitating timely and appropriate intervention.
INTRODUCTION
Among referred patients admitted through Emergency Departments (EDs) in South Korea, urinary tract infection (UTI) is the second most common cause for admission. Moreover, urosepsis is the most common cause of death in patients referred to the ED [1,2]. Ureteral calculi are a major cause of urosepsis, and rapid treatment is often challenging because appropriate drainage (percutaneous nephrostomy [PCN] or ureteral catheterization) may be required in the ED [3-5]. Therefore, for urosepsis associated with ureteral calculi, rapid diagnosis and adequate management are critical for reducing mortality in the ED.
In the newly proposed sepsis definition, the Sequential Organ Failure Assessment (SOFA) score is used to evaluate organ dysfunction and define severity. In this context, initial urosepsis assessment in the ED is critical for early diagnosis and rapid management, including fluid resuscitation and antibiotic therapy adjustment, supported by biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), which help identify patients at sepsis risk [6-8].
Previous studies have demonstrated that biomarkers such as presepsin can predict septic shock and adverse outcomes in patients with UTI [9,10]. Although presepsin is a promising biomarker in patients with UTI, evidence remains limited, particularly for identifying the optimal diagnostic threshold [11]. Moreover, few studies have evaluated presepsin for predicting urosepsis associated with ureteral calculi. Therefore, we investigated the efficacy of presepsin for predicting urosepsis associated with ureteral calculi and compared its performance with that of other inflammatory biomarkers.
MATERIALS AND METHODS
1. Patients and Data Collection
We retrospectively included 64 patients with UTI associated with ureteral calculi who visited the ED between May 2021 and July 2023. Missing data were handled using complete case analysis and patients with missing values for a given variable (e.g., biomarker levels) were excluded from the analysis. Patients were divided into 2 groups: with (n=38) or without (n=26) sepsis. Sepsis was defined as a SOFA score of ≥2 points, according to Sepsis-3 criteria [6]. Patients with chronic kidney disease (estimated glomerular filtration rate<30 mL/min/1.73 m2) were excluded (n=9) because blood presepsin levels increase with decreased renal function [12].
We evaluated patient characteristics (age, sex, European Cooperative Oncology Group performance status scale score, medical history, and upper urinary tract calculi history). And the laboratory tests, including inflammatory markers, were performed as part of the initial evaluation in the ED prior to the administration of antibiotics and PCN. Plasma presepsin levels were measured using a fully automated immunoassay kit (PATHFAST; Mitsubishi Chemical Medience Corp., Japan). Stone characteristics (size and location) were assessed using abdominal computed tomography.
2. Statistical Analysis
For univariable analyses, we compared variables between groups using the Pearson chi-square test or Fisher exact test for categorical variables and Student t-test or Mann-Whitney U-test for continuous variables. Univariable logistic regression analyses were first performed to identify potential predictors of sepsis. Variables with p<0.10 in univariable analysis and those considered clinically relevant were included in the multivariable logistic regression model. Presepsin was analyzed per 100 pg/mL increase to improve interpretability of the odds ratios (ORs). To ensure model stability and prevent overfitting, the number of independent variables in the multivariable model was strictly restricted based on events-per-variable considerations. With 38 sepsis events recorded, the model was limited to a maximum of 3 predictors. Although CRP demonstrated univariable significance, it was excluded from the final model because PCT provides superior diagnostic specificity and accuracy for bacterial sepsis over CRP, which frequently rises nonspecifically during noninfectious systemic inflammation [8]. Therefore, PCT, presepsin, and the quick SOFA (qSOFA) score were selectively retained as the final 3 predictors to optimize both statistical and clinical validity. Receiver operating characteristic (ROC) analysis was used to evaluate predictive accuracy, and the area under the curve (AUC) was calculated for presepsin, CRP, and PCT. The Youden index was used to determine the optimal cutoff values of inflammation markers. Pairwise AUC comparisons for inflammatory biomarkers were conducted using the DeLong test, a nonparametric method for comparing correlated ROC curves. Statistical significance was defined as p<0.05. Statistical analyses were performed using IBM SPSS Statistics ver. 25.0 (IBM Co., USA).
RESULTS
The mean age of all patients was 73.0±10.9 years, and the female proportion was 89.5% (n=34) in the sepsis group and 61.5% (n=16) in the nonsepsis group (p=0.008). All patients underwent PCN in the ED for ureteral calculi. The mean hospital stay was 11.1±5.3 days. Patient baseline characteristics are summarized in Table 1.
The outcomes of baseline characteristics of all patients
Table 2 presents the results of the univariable analysis of laboratory variables. Platelet count, serum albumin level, presepsin level, and PCT level differed significantly between the groups (p<0.05). In univariable logistic regression analysis, qSOFA score (OR, 2.071; p=0.033), CRP (OR, 1.08; p=0.01), PCT (OR, 1.025; p=0.008), and presepsin (per 100-pg/mL increase; OR, 1.354; p=0.001) were significantly associated with sepsis in Table 3. In multivariate logistic regression analysis, presepsin level was an independent predictor of urosepsis associated with ureteral calculi (p=0.003) (Table 4). In the ROC analysis of inflammatory biomarkers, the AUC was higher for presepsin (0.814) than for PCT (0.777) and CRP (0.704) (p<0.05) (Fig. 1). At a cutoff value of 1,202 pg/mL, sensitivity and specificity for sepsis were 57.89% and 100%, respectively (Table 5). In pairwise AUC comparisons across inflammatory biomarkers, no statistically significant differences were observed (p>0.05) (Table 6).
The outcomes of univariable analysis of laboratory data
Univariable logistic regression analysis of inflammatory markers and qSOFA
Multivariate logistic regression analysis of inflammatory markers and qSOFA
Receiver operating characteristic (ROC) analysis comparing the sensitivity and specificity of C-reactive protein (CRP), procalcitonin (PCT), and presepsin for diagnosis of sepsis.
Comparison with each inflammatory biomarker in area under the curve
Pairwise comparisons with each inflammation biomarker in area under the curve
DISCUSSION
Presepsin (soluble CD14-subtype, sCD14-ST) is a 13-kDa fragment generated during breakdown of membrane-bound CD14 in monocytes and macrophages. It is released into the circulation when the innate immune system recognizes bacterial components, particularly after formation of the lipopolysaccharide, lipoprotein binding protein, and CD14 complex and subsequent activation of the toll-like receptor 4 signaling pathway [9]. In this context, presepsin has recently been used as a novel biomarker for the diagnosis of sepsis [13].
The major strength of this study is that it demonstrates the potential role of presepsin as an early predictive biomarker for identifying patients at higher risk of severe urosepsis requiring urgent intervention at ED presentation. Previous studies have evaluated the diagnostic value of presepsin for sepsis which is not associated with specific disease or acute pyelonephritis not associated with ureteral calculi [10,11,14,15]. Also, another study demonstrated that PCT is an early indicator of progression to septic shock associated with ureteral calculi [16]. In this study, we found that plasma presepsin level increased in sepsis, as other biomarkers also increased.
Second, we focused on the potential specificity of presespin as a diagnostic marker compared with other inflammatory biomarkers. Several studies have reported that CRP and PCT levels can increase not only in infection but also in trauma, necrosis, malignancy, burns, and other conditions [17,18]. In contrast to CRP and PCT, presepsin, a byproduct of immune activation, may offer greater specificity for identifying infectious conditions [9]. In this study, presepsin demonstrated an AUC of 0.814, which was higher than that of the other markers evaluated, although the difference was not statistically significant. These findings suggest that presepsin has a diagnostic performance comparable to that of CRP and PCT for identifying urosepsis. Moreover, presepsin may provide additional clinical value when used in combination with established biomarkers such as PCT. At the optimal cutoff value, presepsin showed a relatively low sensitivity (58%) but a high specificity (100%), suggesting its potential usefulness as a rule-in biomarker for urosepsis. However, this finding should be interpreted with caution due to the limited sample size.
Meanwhile, early diagnosis and proper antibiotics administration in sepsis were important to decrease mortality. In Early-Goal Directed Therapy in 2013 Guidelines of the Surviving Sepsis Campaign, early resuscitation of the patients with sepsis during the first 6 hours after recognition and administration of broad-spectrum antibiotics within 1 hour of septic shock [19]. On the basis of this guideline, presepsin may be a helpful biomarker for the early recognition of sepsis due to its early elevation during infection Experimental models have demonstrated detectable presepsin increases within 1–2 hours after endotoxin exposure, with peak concentrations occurring approximately 3 hours before PCT and CRP elevation [17,18,20]. For this reason, in our study, it revealed that presepsin was an independent factor among variables included in the multivariable model. Therefore, presepsin may be a useful biomarker for early sepsis detection, potentially enabling timelier clinical intervention than conventional inflammatory markers.
To manage the obstructed kidney with UTI, urgent decompression, including placement of ureteral stent or PCN should be performed to prevent complications [21]. Some studies demonstrated that ureteral stent and percutaneous drainage are equally effective for decompression of obstructed kidney [22,23]. However, other studies reported that PCN was superior to indwelling ureteral stent for decompression [24,25]. Because of this controversy and controlling confounding related to drainage procedure, we included only patients who underwent PCN as the emergency decompression method for UTI with ureteral calculi.
This study had some limitations. First, this was a single-center retrospective study, which may limit finding reliability. Second, the sample size was relatively small, and all patients underwent PCN that reflects a more severe clinical spectrum of obstructive UTI. These factors may limit the statistical power and generalizability of our findings. However, it is noteworthy that the proportion of patients with sepsis was relatively high in our cohort, suggesting that our findings may be particularly applicable to the management of severe obstructive UTI. Further prospective multicenter studies enrolling a broader patient population are needed to validate these results. Third, biomarker levels were measured only once at presentation, without serial monitoring. Another study reported that presepsin may also be useful for prognostic evaluation [14]. Because presepsin is known to respond rapidly to infection status, serial measurements could have provided additional insight into treatment response and could have supported clinical decision-making, including optimal surgery timing for ureteral calculi. Unfortunately, presepsin levels were not measured after decompression and serial monitoring in this study. Additionally, the timing of PCN decompression was not available in our dataset, which may represent an unmeasured confounding factor, as earlier decompression could potentially influence clinical outcomes including the development of sepsis.
Nevertheless, presepsin may serve as a more specific inflammatory biomarker for the early prediction of sepsis in patients with UTI associated with ureteral calculi, which may help guide treatment planning and early assessment of the need for intensive care. In this study, we demonstrated that presepsin may help predict early sepsis in patients with UTI associated with ureteral calculi. Elevated presepsin levels may help predict sepsis occurrence in patients with UTI associated with ureteral calculi, thereby supporting timely and appropriate intervention. Furthermore, addressing these limitations may enable the establishment of a more precise cutoff value.
Notes
Funding/Support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Research Ethics
This study was approved by the institutional review board (IRB) of Yeungnam University Medical Center (IRB No. YUMC 2026-02-006).
Conflict of Interest
The authors have nothing to disclose.
Author Contribution
Conceptualization: JGH, YUK, HCJ; Data curation: JGH; Formal analysis: JGH, YUK; Methodology: HCJ, YUK; Project administration: HCJ, YUK; Visualization: JGH, YUK; Writing - original draft: JGH; Writing - review & editing: YUK, HCJ.