Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial

Masson et al. Critical Care 2014, 18:R6 http://ccforum.com/content/18/1/R6 RESEARCH Open Access Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial Serge Masson1*†, Pietro Caironi2,3†, Eberhard Spanuth4, Ralf Thomae5, Mauro Panigada3, Gabriela Sangiorgi6, Roberto Fumagalli7, Tommaso Mauri8, Stefano Isgrò7, Caterina Fanizza9, Marilena Romero9, Gianni Tognoni9, Roberto Latini1, and Luciano Gattinoni2,3, on behalf of the ALBIOS Study Investigators† Abstract 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 μg/L (median 3.4 to 45.2) and 10.8 μg/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. 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 * Correspondence: † Equal contributors 1 IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan, Italy Full list of author information is available at the end of the article 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 host’s 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]. © 2014 Masson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Masson et al. Critical Care 2014, 18:R6 http://ccforum.com/content/18/1/R6 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 case–control 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 early goal-directed therapy and the treatment of patients with severe sepsis [1,9]. We selected 50 survivors and 50 nonsurvivors at the time of ICU discharge (21 ± 18 days). The cohorts were matched for age, sex, source center and time of enrollment after confirmation of the inclusion criteria (within 6 hours and between 6 and 24 hours), which were at least one focus of infection (known or suspected), two or more signs of systemic inflammatory reaction syndrome (core temperature >38°C or <36°C; heart rate >90 beats/min; respiratory rate >20 breaths/min or arterial partial pressure of carbon dioxide <32 mmHg or requirement for mechanical ventilation for an acute pathological process; white blood cell count >12,000/μl or <4,000/μl or more than 10% immature neutrophils) and at least one severe, acute sepsis-related organ dysfunction assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score [10]. Exclusion criteria were age younger than 18 years, Page 2 of 9 terminal state, a known adverse reaction to albumin, a proved or suspected and clinically active brain injury, congestive heart failure (New York Heart Association class III o (...truncated)