Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial
Serge Masson
Pietro Caironi
Eberhard Spanuth
Ralf Thomae
Mauro Panigada
Gabriela Sangiorgi
Roberto Fumagalli
Tommaso Mauri
Stefano Isgr
Caterina Fanizza
Marilena Romero
Gianni Tognoni
Roberto Latini
Luciano Gattinoni
on behalf of the ALBIOS Study Investigators
Introduction: Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT). Methods: This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment. Results: Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 g/L (median 3.4 to 45.2) and 10.8 g/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65). Conclusions: In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.
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Introduction
Sepsis is the leading cause of death in critically ill
patients and requires early goal-directed management to
reduce its high burden of mortality and morbidity [1].
During sepsis, the combination of severe infection and
the subsequent nonlocalized inflammatory and
immunemediated systemic responses may result in a clinical
1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, via Giuseppe La
condition with lethality as high as 40% [2]. Despite
efforts to improve early recognition and clinical treatment,
sepsis often evolves to septic shock (that is, reduced
tissue perfusion despite fluid therapy and vasoactive drugs)
and multiorgan failure, which are the most frequent
causes of death in the septic patient. The hosts innate
and adaptive immune responses are fundamental in
defense against the infecting microorganisms, but they
also contribute to the amplification of proinflammatory
mechanisms, coagulation imbalance and endothelial
dysfunction that participate in organ injury [3].
Optimal management requires early goal-oriented
therapies, so, in principle, it could be improved by
individualized circulating biomarkers for early risk
stratification. Circulating biomarkers may help in making the
diagnosis and guiding antimicrobial therapy for patients
with sepsis [4,5], but few have proved to be useful for
individual prognostic stratification. Presepsin (sCD14-ST)
is a soluble N-terminal fragment of the cluster of
differentiation (CD) marker protein CD14, which is released
into the circulation during monocyte activation upon
the recognition of lipopolysaccharide (LPS) from
infectious agents [6]. It shows promise for diagnostic
purposes [7] and powerful prognostic information in septic
patients as early as the time of admission [8]. To date,
no multicenter study has been conducted to evaluate the
prognostic value of presepsin during severe sepsis. We
therefore set out to examine the relationships between
early plasma presepsin concentration and mortality in
patients with severe sepsis and septic shock and
compare its prognostic performance with that of
procalcitonin (PCT).
Materials and methods
Study design
This retrospective casecontrol study was conducted with
data from the multicenter, randomized Albumin Italian
Outcome Sepsis (ALBIOS) trial, which enrolled patients
with severe sepsis or septic shock from 100 ICUs in Italy
(Clinicaltrials.gov Identifier: NCT00707122). The primary
aim of the trial was to verify whether volume replacement
with albumin and the maintenance of serum albumin
levels within the physiologic range during the first 28 days
(or until ICU discharge, whichever came first) improved
28-day and 90-day survival as compared to crystalloids.
Both arms of the study were carried out in accordance
with the Surviving Sepsis Campaign guidelines for earl (...truncated)