Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study

Abstract

Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio.

Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI).

Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients.

Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis.

Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

Keywords: gelsolin; novel biomarker; organ dysfunction; presepsin; presepsin:gelsolin ratio; prognosis; sepsis-3.

Figure 1

PSEP:GSN ratio in control, non-septic and septic patients. PSEP:GSN ratios of control, non-septic and septic patients during follow-up (A). Receiver operating characteristic (ROC) curves of admission laboratory parameters for distinguishing non-sepsis from sepsis (B). Time points: T1: within 12 h after admission; T2: second day; T3: third day. PSEP, presepsin; PSEP:GSN, presepsin:gelsolin ratio; PCT, procalcitonin; SOFA, Sequential Organ Failure Assessment score. n: sample number; n.s.: not significant. ***p < 0.001.

Figure 2

Survival data and predictive power of PSEP:GSN ratio. PSEP:GSN ratio in survivor and in non-survivor septic patients based on 10-day mortality during follow-up (A). Receiver operating characteristic (ROC) curves of admission parameters for predicting 10-day mortality in sepsis (B). Time points: T1: within 12 h after admission; T2: second day; T3: third day. PSEP, presepsin; PSEP:GSN, presepsin:gelsolin ratio; APACHE II, Acute Physiology and Chronic Health Evaluation II score; SAPS II, Simplified Acute Physiology Score II; SOFA, Sequential Organ Failure Assessment score. n: sample number. *p < 0.05; **p < 0.01.

Figure 3

PSEP:GSN ratio in septic patients based on vasopressor requirement. PSEP:GSN ratios of septic patients with different doses of vasopressor requirement during follow-up (A). PSEP:GSN ratios of patients with sepsis and septic shock (B) during follow-up. PSEP:GSN ratios of septic patients needing shorter (≤5 days) and longer (>5 days) vasopressor support during follow-up (C). Receiver operating characteristic (ROC) curves of admission parameters for distinguishing sepsis from septic shock (D) along with discerning septic patients’ shorter (≤5 days) and longer (>5 days) vasopressor requirement (E). Time points: T1: within 12 h after admission; T2: second day; T3: third day. NE, norepinephrine; PSEP, presepsin; PSEP:GSN, presepsin:gelsolin ratio; PCT, procalcitonin; SOFA, Sequential Organ Failure Assessment score. n: sample number. **p < 0.01; ***p < 0.001.

Figure 4

PSEP:GSN ratio in septic patients based on requirements of respiratory support. PSEP:GSN ratios of septic patients with requirements of oxygen supplementation and mechanical ventilation (A), with the latter group having ARDS (B) during follow-up. PSEP:GSN ratios of septic patients having shorter (≤7 days) and longer (>7 days) requirement of mechanical ventilation during follow-up (C). Receiver operating characteristic (ROC) curves of admission parameters for distinguishing septic patients needing oxygen supplementation from mechanical ventilation (D) along with discerning septic patients’ shorter (≤7 days) and longer (>7 days) requirement of mechanical ventilation (E). Time points: T1: within 12 h after admission; T2: second day; T3: third day. ARDS, acute respiratory distress syndrome; PSEP, presepsin; PSEP:GSN, presepsin:gelsolin ratio; PCT, procalcitonin; SOFA, Sequential Organ Failure Assessment score. n: sample number. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 5

PSEP:GSN ratio in sepsis-related AKI. PSEP:GSN ratios of septic non-AKI and sepsis-related AKI patients (A) during follow-up. PSEP:GSN ratios of the individual sepsis-related AKI stages (B) during follow-up. Receiver operating characteristic (ROC) curves of admission laboratory parameters for distinguishing septic non-AKI from sepsis-related AKI state (C). AKI, acute kidney injury; PSEP, presepsin; PSEP:GSN, presepsin:gelsolin ratio; PCT, procalcitonin. Time points: T1: within 12 h after admission; T2: second day; T3: third day. n: sample number. *p < 0.05; **p < 0.01; ***p < 0.001.