Pancreatic Stone Protein: A Novel Biomarker for Sepsis Management in Critical Care

Sepsis remains a leading cause of morbidity and mortality in intensive care units (ICUs), exacerbated by delays in diagnosis and inadequate risk stratification. Despite advances in critical care, conventional biomarkers like procalcitonin (PCT) and C-reactive protein (CRP) often fail to provide timely or specific detection. Pancreatic Stone Protein (PSP), a stress-induced secretory protein, has emerged as a promising biomarker for early sepsis identification and prognosis. Recent evidence demonstrates its superior performance over traditional markers, particularly when measured via rapid point-of-care platforms such as the Abionic abioSCOPE®. This review examines PSP’s biological rationale, clinical utility, and operational impact in critical care, underscoring its alignment with value-based medicine principles.

Introduction

Sepsis, a dysregulated host response to infection, presents a formidable challenge in ICUs due to its heterogeneous clinical course and the limitations of existing diagnostic tools. Current biomarkers, including PCT and CRP, lack sensitivity and specificity in early infection stages, contributing to delayed interventions and suboptimal outcomes. In value-based critical care, where precision, timeliness, and cost-efficiency are paramount, novel solutions are urgently needed.

Pancreatic Stone Protein (PSP) has recently gained attention as a biomarker capable of transforming sepsis workflows. Under physiological conditions, PSP is expressed minimally, but its levels rise sharply during systemic inflammation. When paired with rapid point-of-care testing (e.g., the abioSCOPE®), PSP enables early sepsis detection, optimised resource allocation, and judicious antibiotic use. This article explores PSP’s biological underpinnings, clinical evidence, and practical implications for ICU management.

Biological Rationale for PSP in Sepsis

PSP belongs to the regenerating (Reg) protein family, primarily expressed in the pancreas, gastrointestinal tract, and lungs. During infection or systemic inflammation, its production is upregulated by cytokine cascades and cellular stress. Emerging research suggests PSP modulates immune activation via pattern recognition receptors and neutrophil extracellular trap (NET) formation, positioning it as an upstream mediator of the host response (Ventura and Tissières 2024).

Critically, PSP levels elevate up to 72 hours before clinical sepsis manifestations, offering a vital window for preemptive action. Its kinetics are more rapid and pronounced than those of PCT or CRP, making it particularly suited for time-sensitive ICU decision-making.

Clinical Evidence Supporting PSP’s Role

The diagnostic and prognostic utility of PSP has been validated across diverse critically ill populations. In general ICU cohorts, large prospective studies reveal strong correlations between PSP levels, sepsis severity, organ dysfunction, and mortality. For example, a study of 285 sepsis patients demonstrated that PSP aligned closely with PCT and SOFA scores (AUC: 0.87), while elevated values predicted renal replacement therapy and in-hospital mortality (Lee et al. 2024). Although PSP may not function as an independent predictor, its integration into multimodal risk-stratification tools enhances accuracy, supporting its role as a complementary biomarker.

PSP’s potential is further highlighted in high-risk subgroups. In mechanically ventilated patients, serial PSP measurements detect ventilator-associated pneumonia (VAP) 48 to 72 hours before clinical diagnosis, outperforming CRP and PCT in sensitivity and specificity (Ceccato et al. 2023). This early signal could facilitate preemptive therapy, potentially reducing ICU stays and improving outcomes. Similarly, in patients with acute or chronic liver failure, populations with notoriously unreliable inflammatory markers, PSP levels rise predictably in non-survivors by the fourth day, correlating with renal dysfunction and adverse outcomes (Lopes et al. 2025).

These findings are reinforced by meta-analyses encompassing over 50 clinical studies, which collectively affirm PSP’s early predictive capacity. Comparative analyses consistently rank PSP ahead of or complementary to traditional markers, underscoring its potential within sepsis management bundles aimed at diagnostic precision and antimicrobial stewardship (Ventura et al. 2023).

Operational Impact and Future Directions

The integration of PSP into ICU workflows, particularly via point-of-care platforms, has the potential to significantly enhance sepsis management by enabling real-time, actionable insights. Early PSP-guided interventions may reduce unnecessary antibiotic use, improve resource allocation, and ultimately lower healthcare costs. Future research should focus on standardised cut-off values, protocolised monitoring strategies, and the biomarker’s impact on long-term outcomes.

Conclusion

PSP represents a significant advancement in sepsis biomarker science, bridging critical gaps in early detection and risk stratification. Its rapid kinetics, robust clinical correlations, and compatibility with point-of-care testing align with the demands of modern critical care. As evidence grows, PSP is poised to become a cornerstone of value-based sepsis management in ICUs.

Disclaimer

Point-of-view articles are the sole opinion of the author(s) and are part of the ICU Management & Practice Corporate Engagement or Educational Community Programme.