Clinical trial NCT05060679: Presepsin:Gelsolin Ratio in Sepsis-related Organ Dysfunction
Official title: Presepsin:Gelsolin Ratio, as a Promising Marker of Sepsis-related Organ Dysfunction: a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Acute Kidney Injury Due to Sepsis
Septic Shock
Acute Respiratory Distress Syndrome
Keywords: Sepsis-3
Organ dysfunction
Prognosis
Presepsin
Gelsolin
Presepsin:gelsolin ratio
Novel biomarker
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2021-09-29
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy control individuals (n=23), non-septic ICU patients (n=38) and septic patients (n=65) were enrolled, while the septic group was also investigated based on the occurrence of sepsis-related organ dysfunction (e.g. acute kidney injury, hemodynamic instability, acute respiratory distress syndrome)

Brief summary: In the present study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. Exclusion criteria were patients under 18 years of age, unobtainable consent, end-stage renal disease requiring chronic dialysis or kidney transplantation and patients with malignancies needing palliative care. Not more than one sample (venous blood) was collected from control patients. Plasma presepsin levels were determined by an automated chemiluminescence-based Point of Care instrument while serum gelsolin levels were measured using an automated immune turbidimetric assay. Plasma presepsin concentrations were expressed as pg/mL, while serum gelsolin levels were expressed as mg/L. Data were compared with laboratory and clinical parameters. Patients were categorized by the Sepsis-3 definitions and 10-day mortality data were investigated. Presepsin:gelsolin ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic disturbances, respiratory insufficiency and acute kidney injury (AKI).

Detailed description: Presepsin is the 13-kDa soluble N-terminal fragment of the 55-kDa cluster of differentiation (CD) marker protein CD14, which is the receptor for lipopolysaccharide (LPS) and LPS-binding protein complexes. CD14 is a glycoprotein expressed mostly on the membrane surface of macrophages, monocytes and granulocytes which is released and degraded during inflammation after the recognition of pathogen-associated molecular patterns (PAMP), thus probably resulting in earlier elevation of plasma presepsin (PSEP) levels than the conventional sepsis biomarkers (C-reactive protein, procalcitonin). There is a growing body of evidence indicating increasing PSEP levels as kidney function decreases (e.g. during chronic kidney disease or sepsis-related AKI). Gelsolin (GSN) is a multifunctional protein existing in three different isoforms. Secreted or plasma GSN (MW = 83 kDa) is an essential component of the so-called extracellular actin scavenger system, therefore, decreasing serum GSN levels were reported in various clinical conditions (e.g. severe sepsis, multiple organ dysfunction syndrome (MODS), extensive trauma, acute liver failure, myocardial infarction). As albumin levels also tend to decrease in severe catabolic conditions, the simultaneous measurement of PSEP and GSN could prove to be useful regarding the diagnosis and prognosis of sepsis and sepsis-related organ dysfunction. Therefore, a new potential marker was investigated: the presepsin:gelsolin (PSEP:GSN) ratio. The main focuses of this study were analyzing the time course of PSEP:GSN ratio in non-septic and septic patients, while also investigating its diagnostic and prognostic utility in various sepsis-related organ dysfunctions in contrast to the conventional sepsis markers and clinical prognostic scores.

Eligibility criteria: Inclusion Criteria:

* Non-septic patients needing ICU supportive treatment after major surgical interventions
* Sepsis
* Sepsis-related organ dysfunction (e.g. acute kidney injury, hemodynamic instability, acute respiratory distress syndrome)

Exclusion Criteria:

* under 18 years of age
* unobtainable consent
* end-stage renal disease
* kidney transplantation
* malignancies needing palliative care

Primary outcomes:
measure: Plasma Presepsin concentrations
timeFrame: 3 days
measure: Serum gelsolin concentrations
timeFrame: 3 days
Secondary outcomes:
measure: Presepsin:gelsolin ratios
timeFrame: 5 days
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs
state: Baranya
Study officials:
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Dániel Ragán, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Péter Kustán, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Zoltán Horváth-Szalai, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Balázs Szirmay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Attila Miseta, MD, Dsc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs
name: Gábor Woth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Laboratory Medicine, Medical School, University of Pécs
name: Tamás Kőszegi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs
name: Diána Mühl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: