Presepsin:Gelsolin Ratio in Sepsis-related Organ Dysfunction
Condition: Sepsis; Acute Kidney Injury Due to Sepsis; Septic Shock; Acute Respiratory Distress Syndrome
MeSH terms: Sepsis; Toxemia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Acute Kidney Injury
Study type: Observational

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.
    

Intervention name(s): Supportive therapy at the ICU; Sepsis therapy; Sepsis-related organ dysfunction therapy
Intervention type(s): Other; Other; Other
Intervention description(s): Non-septic ICU patients received adequate supportive treatment (fluid resuscitation, respiratory, anticoagulation, antimicrobial and vasopressor therapy along with sedation, ulcer prophylaxis and nutrition. Blood sampling for non-septic patients were the first (T1) and third (T3) postoperative morning at the ICU. Besides, 23 healthy outpatients were documented without sepsis or sepsis-related organ dysfuntion as a control group.; Patients receiving sepsis therapy followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis and nutrition. Blood samples were collected at the ICU from this patient group at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up.; Patient management of sepsis and sepsis-related organ dysfunction followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis, nutrition and renal replacement therapy (if needed). In this patient group, blood sampling was performed at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up.
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)
      
Biospecimen description: 
      Blood (Serum; Plasma)
    
Keywords: Sepsis-3; Organ dysfunction; Prognosis; Presepsin; Gelsolin; Presepsin:gelsolin ratio; Novel biomarker