Intestinal fatty acid-binding protein (I-FABP) at ICU admission as early biomarker of intestinal injury and predictor of mortality in septic shock.

Authors

Thorben Pape, Pedro David Wendel-Garcia, Nina Rittgerodt, Bahar Nalbant, Jan Hinrichs, Lena S Becker, Anna M Hunkemöller, Jakob Raith, Sören K J Boblitz, Jannik Ruwisch, Pia-Victoria Fangmann, Heiner Wedemeyer, Marius M Hoeper, Christian Bode, Sascha David, Klaus Stahl, Benjamin Seeliger

Published in

Intensive care medicine experimental. Volume 14. Issue 1. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

Septic shock and acute respiratory distress syndrome (ARDS) are major causes of mortality. Intestinal hypoperfusion is a frequent but often unrecognized complication, and the timing and extent of intestinal injury in these syndromes remain unclear. Intestinal fatty acid-binding protein (I-FABP) has emerged as a potential biomarker of intestinal injury. This study aimed to define a clinically relevant I-FABP cutoff for predicting relevant intestinal injury and to assess its association with disease severity and outcome.
We performed a post-hoc analysis combining cohorts of critically ill patients from the prospective EXCHANGE-pilot, the RCT EXCHANGE-1, and the SPARE-14 registry. The analysis included 102 patients with septic shock and/or ARDS, 22 patients with non-occlusive mesenteric ischemia (NOMI) from the REPERFUSE study, and 20 healthy individuals. Circulating I-FABP concentrations were measured by ELISA in plasma samples obtained at ICU admission. Receiver operating characteristic (ROC) analysis was used to define the optimal I-FABP threshold for predicting intestinal hypoperfusion, using patients with NOMI as positive- and healthy individuals as negative controls. Associations between I-FABP, disease severity, and 28-day mortality were analyzed.
ROC analysis identified an initial I-FABP cutoff of 1070 pg/ml (sensitivity 68%, specificity 100%) for the development of intestinal ischemia defined by criteria of manifest NOMI. I-FABP levels at ICU admission were significantly elevated in patients with ARDS and/or septic shock compared with healthy controls (1108 pg/ml (IQR 291-2846) vs. 479 pg/ml (IQR 358-631), p = 0.03), and comparable to those in NOMI patients. Exploratory generalized additive model analyses indicated a non-linear association between I-FABP concentrations and established markers of shock severity. Patients with high I-FABP levels (above 1070 pg/ml) had a higher 28-day mortality (high: 52.9% vs. low: 33.3%, p = 0.02). In a multivariate logistic regression model, I-FABP and SOFA score remained independently associated with 28-day mortality (I-FABP: adjusted OR 1.27 (1.03-1.62), p = 0.023), without independent association of lactate concentration.
Elevated plasma I-FABP may identify undetected intestinal injury in critically ill patients with septic shock and/or ARDS and might be associated with higher 28-day mortality. Additionally, I-FABP might reflect a distinct facet of critical illness that is not fully captured by conventional measures of organ dysfunction or shock severity and I-FABP concentrations ≥ 1070 pg/ml may help identify patients at high risk for intestinal ischemia who could benefit from early therapeutic interventions.

PMID:
42645732
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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