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L-FABP and NGAL are novel biomarkers for detection of abdominal injury and hemorrhagic shock

  • M. Voth
    Correspondence
    Corresponding author at: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt / Main, Germany.
    Affiliations
    Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
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  • R. Verboket
    Affiliations
    Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
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  • D. Henrich
    Affiliations
    Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
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  • I. Marzi
    Affiliations
    Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
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Published:January 02, 2023DOI:https://doi.org/10.1016/j.injury.2023.01.001

      Highlights

      • L-FABP is a novel biomarker for the early detection of abdominal injury and of hemorrhagic shock.
      • L-FABP is specific in the detection of an injury of the kidney and liver.
      • NGAL is a novel biomarker for the detection of abdominal injury and hemorrhagic shock.
      • NGAL failed to be specific in the detection of an injury of the liver and/or the kidney.

      Abstract

      Introduction

      Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries.

      Patients and Methods

      Traumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury (“Abd”) and 10 patients had an abdominal injury with hemorrhagic shock (“HS Abd”). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 (“noAbd”) were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma.

      Results

      All patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in “HS Abd” group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to “noAbd” group (36.4 ng/ml [IQR=14.8–88.5]), and to “Abd” group (41.4 ng/ml [IQR=18.0–235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group “Abd” were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to “noAbd” (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in “HS Abd” group (115.9 ng/ml [IQR=90.6–163.8]) compared to “noAbd” group (58.5 ng/ml [IQR=41.0–89.6],p<0.001) and “Abd” group (70.5 ng/ml [IQR=53.3–115.5], p<0.05). The group “Abd” showed significant higher median NGAL levels compared to “noAbd”, p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock.

      Conclusion

      :L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.

      Keywords

      Abbreviations:

      Abd (Patients with abdominal injury), AIS (Abbreviated Injury Scale), ALT (aspartate transferase), AST (alanine transferase), AUC (Area under the curve), CI (Confidence interval), ER (Emergency Room), FFP (Fresh frozen plasma), H-FABP (Heart-type fatty acid binding protein), Hb (Hemoglobin), HS Abd (Patients with hemorrhagic shock and abdominal injury), Intestinal (isolated injuries of the intestine), ICU (Intensive care unit), IQR (Interquartile Range), IL-6 (interleukin-6), INR (International normalized ratio), ISS (Injury Severity Score), Kidney (isolated injuries of the kidney), L-FABP (Liver fatty acid-binding protein), Liver (isolated injuries of the liver), MAP (Mean arterial pressure), MODS (Multiple organ dysfunction syndrome), NGAL (neutrophil gelatinase-associated lipocalin), noAbd (Patients with hemorrhagic shock and without abdominal injury), PLT (Platelets), NPV (Negative predictive value), PPV (Positive predictive value), PRBC (Packed red blood cells), PTT (Partial thromboplastin time), ROC (Receiver operator characteristic curves), SBP (Systolic blood pressure), SI (Shock index), SIRS (Systemic inflammatory distress syndrome), Spleen (isolated injuries of the spleen)
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      References

        • Nast-Kolb D.
        • Waydhas C.
        • Kastl S.
        • Duswald K.H.
        • Schweiberer L.
        The role of an abdominal injury in follow-up of polytrauma patients.
        Chirurg. 1993; 64: 552-559
        • Enderson B.L.
        • Maull K.I.
        Missed injuries. The trauma surgeon's nemesis.
        Surg Clin North Am. 1991; 71: 399-418
        • Osborn T.M.
        • Tracy J.K.
        • Dunne J.R.
        • Pasquale M.
        • Napolitano L.M.
        Epidemiology of sepsis in patients with traumatic injury.
        Crit Care Med. 2005; 32: 2234-2240
        • Moore F.A.
        The role of the gastrointestinal tract in postinjury multiple organ failure.
        Am J Surg. 2000; 178: 449-453
        • Thuijls G.
        • de Haan J.-.J.
        • Derikx J.P.M.
        • Daissormont I.
        • Hadfoune M.
        • Heineman E.
        • et al.
        Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock.
        Shock. 2008; 31: 164-169
        • Derikx J.P.M.
        • Poeze M.
        • van Bijnen A.A.
        • Buurman W.A.
        • Heineman E.
        Evidence for intestinal and liver epithelial cell injury in the early phase of sepsis.
        Shock. 2007; 28: 544-548
        • Deitch E.A.
        • Xu D.
        • Kaise V.L.
        Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review.
        Front Biosci. 2006; 11: 520-528
        • Fink M.P.
        • Delude R.L.
        Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level.
        Crit Care Clin. 2005; 21: 177-196
        • Van Leeuwen P.A.
        • Boermeester M.A.
        • Houdijk A.P.
        • Ferwerda C.C.
        • Cuesta M.A.
        • Meyer S.
        • et al.
        Clinical significance of translocation.
        Gut. 1994; 35: S28-S34
        • Waydhas C.
        • Nast-Kolb D.
        • Jochum M.
        • Trupka A.
        • Lenk S.
        • Fritz H.
        • et al.
        Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma.
        Arch Surg. 1992; 127: 460-467
        • Keel M.
        • Trentz O.
        Pathophysiology of polytrauma.
        Injury. 2005; 36: 691-709
        • Walcher F.
        Präklinische sonographie.
        Springer, 2003
        • Liu M.
        • Lee C.H.
        • FK P'eng
        Prospective comparison of diagnostic peritoneal lavage, computed tomographic scanning, and ultrasonography for the diagnosis of blunt abdominal trauma.
        J Trauma. 1993; 35: 267-270
        • Nural M.S.
        • Yardan T.
        • Güven H.
        • Baydin A.
        Diagnostic value of ultrasonography in the evaluation of blunt abdominal trauma.
        Dirjournalorg. 2005;
        • Sherck J.
        • Shatney C.
        • Sensaki K.
        • Selivanov V.
        The accuracy of computed tomography in the diagnosis of blunt small-bowel perforation.
        Am J Surg. 1994; 168: 670-675
        • Glatz J.F.
        • van der Vusse G.J.
        Cellular fatty acid-binding proteins: their function and physiological significance.
        Prog Lipid Res. 1996; 35: 243-282
        • Pelsers M.M.A.L.
        • Hermens W.T.
        • Glatz J.F.C.
        Fatty acid-binding proteins as plasma markers of tissue injury.
        Clin Chim Acta. 2005; 352: 15-35
        • Banaszak L.
        • Winter N.
        • Xu Z.
        • Bernlohr D.A.
        • Cowan S.
        • Jones T.A.
        Lipid-binding proteins: a family of fatty acid and retinoid transport proteins.
        Adv Protein Chem. 1994; 45: 89-151
        • Ockner R.K.
        • Manning J.A.
        • Poppenhausen R.B.
        • Ho W.K.
        A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium, and other tissues.
        Science. 1972; 177: 56-58
        • Pelsers M.M.A.L.
        • Namiot Z.
        • Kisielewski W.
        • Namiot A.
        • Januszkiewicz M.
        • Hermens W.T.
        • et al.
        Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility.
        Clin Biochem. 2003; 36: 529-535
        • Guthmann F.
        • Börchers T.
        • Wolfrum C.
        • Wustrack T.
        • Bartholomäus S.
        • Spener F.
        Plasma concentration of intestinal- and liver-FABP in neonates suffering from necrotizing enterocolitis and in healthy preterm neonates.
        Mol Cell Biochem. 2002; 239: 227-234
        • Pelsers M.
        • Morovat A.
        • Alexander G.
        Liver fatty acid-binding protein as a sensitive serum marker of acute hepatocellular damage in liver transplant recipients.
        Academicoupcom. 2002;
        • Monbaliu D.
        • De Vries B.
        • Crabbe T.
        • Van Heurn E.
        Liver fatty acid-binding protein: an early and sensitive plasma marker of hepatocellular damage and a reliable predictor of graft viability after liver transplantation from non-heart-beating donors.
        Elsevier, 2005
        • Kamijo A.
        • Sugaya T.
        • Hikawa A.
        • Yamanouchi M.
        Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease.
        Springer, 2006
        • Negishi K.
        • Noiri E.
        • Doi K.
        • Maeda R.
        Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.
        Elsevier, 2009
        • Noiri E.
        • Doi K.
        • Negishi K.
        • Tanaka T.
        Urinary fatty acid-binding protein 1: an early predictive biomarker of kidney injury.
        Journalsphysiologyorg. 2009;
        • Voth M.
        • Holzberger S.
        • Auner B.
        • Henrich D.
        • Marzi I.
        • Relja B.
        I-FABP and L-FABP are early markers for abdominal injury with limited prognostic value for secondary organ failures in the post-traumatic course.
        Clin Chem Lab Med. 2014; 53: 771-780
        • Relja B.
        • Szermutzky M.
        • Henrich D.
        • Maier M.
        • De Haan J.-.J.
        • Lubbers T.
        • et al.
        Intestinal-FABP and Liver-FABP: novel markers for severe abdominal injury.
        Acad Emerg Med. 2010; 17: 729-735
        • Bolignano D.
        • Donato V.
        • Coppolino G.
        • Campo S.
        Neutrophil gelatinase–associated lipocalin (NGAL) as a marker of kidney damage.
        Elsevier, 2008
        • Kjeldsen L.
        • Johnsen A.H.
        • Sengeløv H.
        Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase.
        ASBMB, 1993
        • Devarajan P.
        Emerging biomarkers of acute kidney injury.
        Kargercom, 2007
        • Kim S.
        • Kim H.J.
        • Ahn H.S.
        • Song J.Y.
        • Um T.H.
        • Cho C.R.
        Is plasma neutrophil gelatinase-associated lipocalin a predictive biomarker for acute kidney injury in sepsis patients? A systematic review and meta-analysis.
        Elsevier, 2016
        • Supavekin S.
        • Zhang W.
        • Kucherlapati R.
        • Kaskel F.J.
        Differential gene expression following early renal ischemia/reperfusion.
        Elsevier, 2003
        • Mishra J.
        • Ma Q.
        • Prada A.
        • Mitsnefes M.
        Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury.
        Am Soc Nephrol. 2003;
        • Fodor R.
        • Grigorescu B.
        • Veres M.
        Plasma neutrophil gelatinase associated lipocalin (NGAL)–early biomarker for acute kidney injury in critically ill patients.
        Ncbinlmnihgov. 2015;
        • Mishra J.
        • Dent C.
        • Tarabishi R.
        • Mitsnefes M.M.
        • Ma Q.
        • Kelly C.
        • et al.
        Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.
        Lancet. 2005; 365: 1231-1238
        • Elm von E.
        • Altman D.G.
        • Egger M.
        • Pocock S.J.
        • Gøtzsche P.C.
        • Vandenbroucke J.P.
        The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. 12. 2014: 1495-1499
        • Baker S.P.
        • O'Neill B.
        • Haddon W.
        • Long W.B.
        The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care.
        J Trauma. 1974; 14: 187-196
        • Dunham C.M.
        • Siegel J.H.
        • Weireter L.
        • Fabian M.
        • Goodarzi S.
        • Guadalupi P.
        • et al.
        Oxygen debt and metabolic acidemia as quantitative predictors of mortality and the severity of the ischemic insult in hemorrhagic shock.
        Crit Care Med. 1991; 19: 231-243
        • Rixen D.
        • Raum M.
        • Holzgraefe B.
        • Sauerland S.
        • Nagelschmidt M.
        • Neugebauer E.A.
        A pig hemorrhagic shock model: oxygen debt and metabolic acidemia as indicators of severity.
        Shock. 2001; 16: 239-244
        • Harrois A.
        • Baudry N.
        • Huet O.
        • Kato H.
        • Lohez M.
        • Ziol M.
        • et al.
        Synergistic deleterious effect of hypoxemia and hypovolemia on microcirculation in intestinal villi*.
        Crit Care Med. 2013; 41: e376-e384
        • Timmermans K.
        • Sir Ö.
        • Kox M.
        • Vaneker M.
        • de Jong C.
        • Gerretsen J.
        • et al.
        Circulating iFABP Levels as a Marker of Intestinal Damage in Trauma Patients.
        Shock. 2015; 43: 117
        • de Haan J.J.
        • Lubbers T.
        • Derikx J.P.
        • Relja B.
        • Henrich D.
        • Greve J.-.W.
        • et al.
        Rapid development of intestinal cell damage following severe trauma: a prospective observational cohort study.
        Crit Care. 2009; 13: R86
        • Derikx J.P.M.
        • Schellekens D.H.S.M.
        • Acosta S.
        Serological markers for human intestinal ischemia: a systematic review.
        Best Pract Res Clin Gastroenterol. 2017; 31: 69-74
        • Powell A.
        • Armstrong P.
        Plasma biomarkers for early diagnosis of acute intestinal ischemia.
        Semin Vasc Surg. 2015; 27: 170-175
        • Voth M.
        • Lustenberger T.
        • Relja B.
        Is I-FABP not only a marker for the detection abdominal injury but also of hemorrhagic shock in severely injured trauma patients?.
        Wjesbiomedcentralcom. 2019;
        • Surgeons C.A.C.O.
        American College of Surgeons Committee on Trauma: advanced trauma life support courses.
        2013
        • Davis J.W.
        • Shackford S.R.
        • Mackersie R.C.
        • Hoyt D.B.
        Base deficit as a guide to volume resuscitation.
        J Trauma. 1988; 28: 1464-1467
        • Huckabee W.E.
        Abnormal resting blood lactate.
        Am. J. Med. 1961; 30: 840
        • Davis J.W.
        • Shackford S.R.
        • Holbrook T.L.
        Base deficit as a sensitive indicator of compensated shock and tissue oxygen utilization.
        Surg Gynecol Obstet. 1991; 173: 473-476
        • Broder G.
        • Weil M.H.
        Excess lactate: an index of reversibility of shock in human patients.
        Science. 1964;
        • Baron B.J.
        • Scalea T.M.
        Acute blood loss.
        Emerg Med Clin North Am. 1996; 14: 35-55
        • Makris K.
        • Markou N.
        • Evodia E.
        Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients.
        Degruytercom. 2009;
        • Makris K.
        • Kafkas N.
        Neutrophil gelatinase-associated lipocalin in acute kidney injury.
        Booksgooglecom. 2012;
        • Rashidi H.H.
        • Sen S.
        • Palmieri T.L.
        • Blackmon T.
        • Wajda J.
        Early recognition of burn-and trauma-related acute kidney injury: a pilot comparison of machine learning techniques.
        Naturecom. 2020;
        • Bolignano D.
        • Lacquaniti A.
        • Coppolino G.
        Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients.
        Kargercom, 2009
        • Bakal Ü.
        • Sarac M.
        • Tartar T.
        • Kaman D.
        A study of the utility of novel non-invasive urinary and serum biomarkers of blunt kidney injury in a rat model: NGAL, KIM-1, and IL-18.
        Ncbinlmnihgov. 2019;
        • Kokorin V.A.
        • Arefiev M.N.
        • Levchouk N.N.
        • Gordeev I.G.
        Diagnostic value of qualitative bedside heart-type fatty acid-binding protein tests compared with cardiac troponin assays in patients with suspected acute coronary syndrome.
        Pol Arch Intern Med. 2018; 128: 623-625
        • Chan C.P.Y.
        • Wan T.S.M.
        • Watkins K.L.
        • Pelsers M.M.A.L.
        • Van der Voort D.
        • Tang F.P.W.
        • et al.
        Rapid analysis of fatty acid-binding proteins with immunosensors and immunotests for early monitoring of tissue injury.
        Biosens Bioelectron. 2004; 20: 2566-2580