Urinary Intestinal Fatty Acid-binding Protein Research Articles

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

The Association Between Intraoperative Compromised Intestinal Integrity and Postoperative Complications in Cancer Patients

BackgroundBecause of perioperative splanchnic hypoperfusion, the gut wall becomes more permeable for intraluminal microbes to enter the splanchnic circulation, possibly contributing to development of complications. Hypoperfusion-related injured enterocytes release intestinal fatty acid binding protein (I-FABP) into plasma, which is used as proxy of intestinal integrity. This study investigates the occurrence of intestinal integrity loss during oncologic surgery, measured by I-FABP change. Secondary the relationship between compromised intestinal integrity, and related variables and complications were studied.MethodsPatients undergoing oncologic surgery from prospective cohort studies were included. Urine I-FABP samples were collected preoperatively (T0) and at wound closure (T1), and in a subgroup on Day 1 (D1) and Day 2 (D2) postoperatively. I-FABP dynamics were investigated and logistic regression analyses were performed to study the association between I-FABP levels and patient-related, surgical variables and complications.ResultsA total of 297 patients were included with median age of 70 years. Median I-FABP value increased from 80.0 pg/mL at T0 (interquartile range [IQR] 38.0–142.0) to 115 pg/mL at T1 (IQR 48.0–198.0) (p < 0.05). Age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08) and anesthesia time (OR 1.13, 95% CI 1.02–1.25) were related to stronger I-FABP increase. When comparing I-FABP change in patients experiencing any complications versus no complications, relative I-FABP change at T1 was 145% of T0 (IQR 86–260) versus 113% (IQR 44–184) respectively (p < 0.05).ConclusionsA significant change in I-FABP levels was seen perioperatively indicating compromised intestinal integrity. Age and anesthesia time were related to higher I-FABP increase. In patients experiencing postoperative complications, a higher I-FABP increase was found.

Diagnostic accuracy of biomarkers to detect acute mesenteric ischaemia in adult patients: a systematic review and meta-analysis

BackgroundAcute mesenteric ischaemia (AMI) is a disease with different pathophysiological mechanisms, leading to a life-threatening condition that is difficult to diagnose based solely on clinical signs. Despite widely acknowledged need for biomarkers in diagnosis of AMI, a broad systematic review on all studied biomarkers in different types of AMI is currently lacking. The aim of this study was to estimate the diagnostic accuracy of all potential biomarkers of AMI studied in humans.MethodsA systematic literature search in PubMed, The Cochrane Library, Web of Science and Scopus was conducted in December 2022. Studies assessing potential biomarkers of AMI in (at least 10) adult patients and reporting their diagnostic accuracy were included. Meta-analyses of biomarkers’ sensitivity, specificity, and positive and negative likelihood ratios were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed with the QUADAS-2 tool.ResultsSeventy-five studies including a total of 9914 patients assessed 18 different biomarkers in serum/plasma and one in urine (each reported in at least two studies), which were included in meta-analyses. None of the biomarkers reached a conclusive level for accurate prediction. The best predictive value overall (all studies with any type and stage of AMI pooled) was observed for Ischaemia-modified albumin (2 studies, sensitivity 94.7 and specificity 90.5), interleukin-6 (n = 4, 96.3 and 82.6), procalcitonin (n = 6, 80.1 and 86.7), and intestinal fatty acid-binding protein (I-FABP) measured in serum (n = 16, 73.9 and 90.5) or in urine (n = 4, 87.9 and 78.9). In assessment of transmural mesenteric ischaemia, urinary I-FABP (n = 2, 92.3 and 85.2) and D-dimer (n = 3, 87.6 and 83.6) showed moderate predictive value. Overall risk of bias was high, mainly because of selected study populations and unclear timings of the biomarker measurements after onset of symptoms. Combinations of biomarkers were rarely studied, not allowing meta-analyses.ConclusionsNone of the studied biomarkers had sufficient sensitivity and specificity to diagnose AMI, although some biomarkers showed moderate predictive accuracy. Future studies should focus on timing of measurements of biomarkers, distinguishing between early stage and transmural necrosis, and between different types of AMI. Additionally, studies on combinations of biomarkers are warranted.PROSPERO registration: CRD42022379341.

I-FABP as a Potential Marker for Intestinal Barrier Loss in Porcine Polytrauma.

Polytrauma and concomitant hemorrhagic shock can lead to intestinal damage and subsequent multiple organ dysfunction syndrome. The intestinal fatty acid-binding protein (I-FABP) is expressed in the intestine and appears quickly in the circulation after intestinal epithelial cell damage. This porcine animal study investigates the I-FABP dynamics in plasma and urine after polytrauma. Furthermore, it evaluates to what extent I-FABP can also act as a marker of intestinal damage in a porcine polytrauma model. Eight pigs (Sus scrofa) were subjected to polytrauma which consisted of lung contusion, tibial fracture, liver laceration, and hemorrhagic shock followed by blood and fluid resuscitation and fracture fixation with an external fixator. Eight sham animals were identically instrumented but not injured. Afterwards, intensive care treatment including mechanical ventilation for 72 h followed. I-FABP levels in blood and urine were determined by ELISA. In addition, immunohistological staining for I-FABP, active caspase-3 and myeloperoxidase were performed after 72 h. Plasma and urine I-FABP levels were significantly increased shortly after trauma. I-FABP expression in intestinal tissue showed significantly lower expression in polytraumatized animals vs. sham. Caspase-3 and myeloperoxidase expression in the immunohistological examination were significantly higher in the jejunum and ileum of polytraumatized animals compared to sham animals. This study confirms a loss of intestinal barrier after polytrauma which is indicated by increased I-FABP levels in plasma and urine as well as decreased I-FABP levels in immunohistological staining of the intestine.

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

The aim of the study was to assess intestinal inflammatory measures, urinary intestinal fatty acid-binding protein (IFABP), and fecal calprotectin (FC) by gestational age (GA) and postmenstrual age (PMA) and determine the association between intestinal inflammation and growth in preterm infants from birth to hospital discharge. We hypothesized that intestinal inflammation is associated with adverse growth in preterm infants. We assayed repeated measures of IFABP and FC in 72 hospitalized preterm infants (<34 weeks' gestation). We calculated weight and length z scores at birth and discharge using the Fenton growth reference. Associations between mean IFABP or FC, growth z scores at discharge, and growth faltering (weight or length z score difference <-0.8 from birth to discharge) were assessed using mixed linear and logistic regression models, adjusted for intrafamilial correlation and potential confounders: GA, sex, birth z score, race/ethnicity, and maternal age. Mean IFABP was greater among infants born at earlier GA and decreased with increasing PMA. Mean FC did not vary by GA or PMA. Higher mean IFABP and FC were associated with lower discharge growth z scores and greater likelihood of growth faltering significant only for mean IFABP and discharge length z score (β = -0.353, 95% confidence interval [CI]: -0.704 to -0.002) and mean IFABP and length faltering (odds ratio [OR] 1.99, P = 0.018). Intestinal inflammation, measured by IFABP, was associated with lower length z scores and length faltering at discharge. Interventions to prevent intestinal inflammation may improve linear growth among preterm infants.

Neonatal anemia relates to intestinal injury in preterm infants.

BackgroundAnemia is associated with decreased tissue oxygenation in preterm infants and may contribute to developing necrotizing enterocolitis (NEC). We aimed to investigate whether hemoglobin level is associated with intestinal injury, by comparing anemic infants 10 days prior to red blood cell (RBC) transfusion with non-anemic controls.MethodsA nested case–control study in which we matched anemic preterms (gestational age (GA) < 32 weeks) with non-anemic controls (1:1), based on GA, birth weight (BW), and postnatal age. We measured urinary intestinal fatty acid-binding protein, I-FABP, marker for intestinal injury, twice weekly. Simultaneously, we assessed splanchnic oxygen saturation (rsSO2) and rsSO2 variability.ResultsThirty-six cases and 36 controls were included (median GA 27.6 weeks, BW 1020 grams). Median I-FABP level was higher in cases from 6 days to 24-h before transfusion (median ranging: 4749–8064 pg/ml versus 2194–3751 pg/ml). RsSO2 and rsSO2 variability were lower in cases than controls shortly before transfusion. Hemoglobin levels correlated negatively with rsSO2 and rsSO2 variability in cases, and negatively with I-FABP in cases and controls together.ConclusionsUrinary I-FABP levels were higher in anemic infants before RBC transfusion than in non-anemic matched controls, suggesting intestinal injury associated with anemia. This may predispose to NEC in some anemic preterm infants.Impact Anemia is a common comorbidity in preterm infants and may lead to impaired splanchnic oxygen saturation and intestinal tissue hypoxia, a proposed mechanism for NEC.Lower hemoglobin level is associated with higher urinary I-FABP levels, a marker for intestinal injury, both in anemic preterm infants and in cases and controls together.Lower splanchnic oxygen saturation and reduction of its variability are associated with higher urinary I-FABP levels in anemic preterm infants before their first RBC transfusion.These results support the hypothesis that anemia in very preterm infants results in intestinal cell injury, which may precede NEC development in some.

Clinical investigation of intestinal fatty acid-binding protein (I-FABP) as a biomarker of SARS-CoV-2 infection

ObjectivesSARS-CoV-2 exhibits tropism for the gastrointestinal tract; however, lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown.MethodsSARS-CoV-2 patients were enrolled in 5 medical centres in São Paulo, Brazil and their clinical characteristics and laboratory findings recorded. At admission, day 7 and day 14 of hospitalisation, plasma and urine samples were collected, and cytokine levels and intestinal fatty acid-binding protein (I-FABP) concentrations measured.ResultsCOVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission (n=283; P<0.001), day 7 (n=142; P<0.01) and day 14 (n=75; P<0.01) of hospitalisation. Critically ill patients and nonsurvivors showed higher I-FABP concentrations compared with patients with less severe illness. At admission, infected patients demonstrated enhanced production of plasma interferon (IFN)-γ and interleukin (IL)-6. The receiver operating characteristic curve suggested I-FABP as a biomarker for COVID-19 disease severity at admission (P<0.0001; Youden index=6.89; area under the curve=0.699). Patients with I-FABP ≥6.89 showed higher IL-6 and C-reactive protein levels (P<0.001) at admission and had a prolonged length of hospital stay.ConclusionsOur findings revealed damage to enterocytes in SARS-CoV-2 infection, which is associated with illness severity, poor prognosis and exacerbated inflammatory response.

The Physiologic Significance of Early Urinary Intestinal Fatty Acid Binding Protein Levels in Preterm Infants: A Prospective Cohort Study.

Intestinal fatty acid binding protein (I-FABP) is released from mature enterocytes when cell membrane integrity is disrupted. This study aimed to prospectively investigate the physiologic significance of early urinary I-FABP and whether it might reflect intestinal compromise in preterm infants. We conducted a prospective cohort study of 100 preterm infants weighing <1250 g and collected serial urine samples at 12, 24, and 48 h after birth. The correlations between initial urinary I-FABP/urinary creatinine (creatinineu) levels and associated factors were analyzed. Among 100 patients, 15 were diagnosed with meconium obstruction of prematurity, and five were diagnosed with necrotizing enterocolitis during the hospital stay. Early urinary I-FABP/creatinineu levels were inversely correlated with both gestational age (Spearman’s rank correlation coefficient (Rs) −0.381, p < 0.01) and birth weight ((Rs) −0.424, p < 0.01). Early urinary I-FABP/creatinineu levels were associated with cord pH ((Rs) −0.436, p < 0.01) and base excess ((Rs) −0.258, p = 0.021). There were significantly positive correlations between early urinary I-FABP/creatinineu levels and the time to full enteral feeding in preterm infants without specific intestinal morbidities. Therefore, a more premature gut with acute perinatal ischemia is expected to exhibit increased I-FABP levels shortly after birth. Because of small sample size, further large-scale studies are needed.

Prevalence of intra-abdominal hypertension and markers for associated complications among severe burn patients: a multicenter prospective cohort study (BURNIAH study)

PurposeSeverely burned patients are at risk for intra-abdominal hypertension (IAH) and associated complications such as organ failure, abdominal compartment syndrome (ACS), and death. The aim of this study was to determine the prevalence of IAH among severely burned patients. The secondary aim was to determine the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications.MethodsA prospective observational study was performed in two burn centers in the Netherlands. Fifty-eight patients with burn injuries ≥ 15% of total body surface area (TBSA) were included. Intra-abdominal pressure (IAP) and urinary I-FABP, measured every 6 h during 72 h. Prevalence of IAH, new organ failure and ACS, and the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications were determined.ResultsThirty-one (53%) patients developed IAH, 17 (29%) patients developed new organ failure, but no patients developed ACS. Patients had burns of 29% (P25–P75 19–42%) TBSA. Ln-transformed levels of urinary I-FABP and IAP were inversely correlated with an estimate of − 0.06 (95% CI − 0.10 to − 0.02; p = 0.002). Maximal urinary I-FABP levels had a fair discriminatory ability for patients with IAH with an area under the ROC curve of 74% (p = 0.001). Urinary I-FABP levels had no predictive value for IAH or new organ failure in severe burn patients.ConclusionsThe prevalence of IAH among patients with ≥ 15% TBSA burned was 53%. None of the patients developed ACS. A relevant diagnostic or predictive value of I-FABP levels in identifying patients at risk for IAH-related complications, could not be demonstrated.Level of evidenceLevel III, epidemiologic and diagnostic prospective observational study.

Intestinal fatty acid binding protein as a predictor for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; a prospective cohort study (I-Fabulous study).

Critically ill patients are at risk for intra-abdominal hypertension (IAH) and related complications such as organ failure, abdominal compartment syndrome (ACS), and death. This study aimed to determine the value of urinary and serum intestinal fatty acid binding protein (I-FABP) levels as early marker for IAH-associated complications. A prospective observational study was conducted in two academic institutional mixed medical-surgical ICUs in the Netherlands. Adult patients admitted to the ICU with two or more risk factors for IAH (198) were included. Urinary and serum I-FABP and intra-abdominal pressure (IAP) were measured every six hours during 72h. Fifteen (8%) patients developed ACS and 74 (37%) developed new organ failure. I-FABP and IAP were positively correlated. Patients who developed ACS had higher median baseline levels of urinary I-FABP (235(P25-P75 85-1747)μg/g creat) than patients with IAH who did not develop ACS (87(P25-P75 33-246)μg/g, p=0.037). With an odds ratio of 1.00, neither urinary nor serum I-FABP indicated increased risk for developing new organ failure or ACS. A relevant diagnostic value of I-FABP levels for identifying individual patients at risk for intra-abdominal pressure related complications could not be demonstrated.

Urinary Intestinal Fatty Acid Binding Protein for Diagnosis of Necrotizing Enterocolitis

This study was conducted to compare the urinary levels of intestinal fatty acid binding protein (I-FABP) and I-FABP: Cr (creatinine) between neonates with necrotising enterocolitis and gestation matched healthy controls. 24 neonates with stage 1, 25 with stage 2 and 3 necrotizing enterocolitis, and 25 gestation matched (32.9 wk) controls were compared. Single spot urine sample was collected for estimating the IFABP and creatinine levels. Median (IQR) value of urinary I-FABP were higher in those with stage 2, 3 NEC [2773 (2417.7- 2820)] than stage 1 NEC [1164 pg/mL (1341.5 - 2213.4)] and controls [413 (113 - 729.7); pg/mL] (P<0.001). Urinary I-FABP: Cr levels of 3.6 pg/mmoL had a sensitivity and specificity of 96% and 99.5%, respectively in diagnosing stage 2/3 NEC. Urinary IFABP: Creatine ratio of 3.6 pg/mmoL is highly specific for stage 2 and 3 NEC.

Effects of an 8-Week Protein Supplementation Regimen with Hyperimmunized Cow Milk on Exercise-Induced Organ Damage and Inflammation in Male Runners: A Randomized, Placebo Controlled, Cross-Over Study

Prolonged strenuous exercise may induce inflammation, cause changes in gastrointestinal permeability, and lead to other unfavorable biological changes and diseases. Nutritional approaches have been used to prevent exercise-induced inflammatory responses and gastrointestinal disorders. Hyperimmunized milk, obtained by immunizing cows against specific antigens, promotes the development of immunity against pathogens, promotes anti-inflammatory effects, and protects intestinal function. Immune protein (IMP) is a concentrated product of hyperimmunized milk and is a more promising means of supplementation to protect against acute infections and inflammation. To determine whether IMP has protective properties against exercise-induced gastrointestinal dysfunction and inflammation, we examined biochemical markers, intestinal damage markers, and pro-/anti-inflammatory profiles of young male runners using a randomized, placebo controlled, cross-over design. Urine samples were collected and used for measurements of creatinine, N-acetyl-β-d-glucosaminidase, osmotic pressure, and specific gravity. Titin was measured as a muscle damage marker. Further, urine concentrations of complement 5a, calprotectin, fractalkine, myeloperoxidase, macrophage colony-stimulating factor, monocyte chemotactic protein-1, intestinal fatty acid binding protein (I-FABP), interferon (IFN)-γ, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays. We demonstrated that urine osmotic pressure, urine specific gravity, I-FABP, IFN-γ, IL-1β, and TNF-α were reduced by 8 weeks of IMP supplementation, indicating that IMP may have potential in preventing strenuous exercise-induced renal dysfunction, increased intestinal permeability, and inflammation. Thus, IMP supplementation may be a feasible nutritional approach for the prevention of unfavorable exercise-induced symptoms.

Diagnostic accuracy of urinary intestinal fatty acid binding protein in detecting colorectal anastomotic leakage.

Anastomotic leakage (AL) remains a severe complication following colorectal surgery, having a negative impact on both short- and long-term outcomes. Since timely detection could enable early intervention, there is a need for the development of novel and accurate, preferably, non-invasive markers. The aim of this study was to investigate whether urinary intestinal fatty acid binding protein (I-FABP) could serve as such a marker. This prospective multicenter cross-sectional phase two diagnostic study was conducted at four centers in the Netherlands between March 2015 and November 2016. Urine samples of 15 patients with confirmed colorectal AL and 19 patients without colorectal AL on postoperative day 3 were included. Urinary I-FABP levels were determined using enzyme-linked immunosorbent assays and adjusted for urinary creatinine to compensate for renal dysfunction. Urinary I-FABP levels were significantly elevated in patients with confirmed AL compared to patients without AL on postoperative day 3 (median: 2.570ng/ml vs 0.809ng/ml, p = 0.006). The area under the receiver operating characteristics curve (AUROC) was 0.775, yielding a sensitivity of 80% and specificity of 74% at the optimal cutoff point (> 1.589ng/ml). This difference remained significant after calculation of I-FABP/creatinine ratios (median: 0.564ng/µmol vs. 0.158ng/µmol, p = 0.040), with an AUROC of 0.709, sensitivity of 60% and specificity of 90% at the optimal cutoff point (> 0.469ng/µmol). Levels of urinary I-FABP and urinary I-FABP/creatinine were significantly elevated in patients with confirmed AL following colorectal surgery, suggesting their potential as a non-invasive biomarker for colorectal anastomotic leakage.

Urinary Intestinal Fatty Acid Binding Protein “IFABP” as a Marker for Gut Maturation in Preterm Babies

Objective: Formula-fed premature babies have a higher incidence of developing necrotizing enterocolitis (NEC) than breast-fed babies which may be caused by breast milk induced gut maturation. The effect of breast milk on maturation of the gut has been widely studied in animal models and recently in humans. The Aim of this Study: Is to evaluate the effects of breast-feeding on maturation of the intestine in premature babies by measuring the postnatal values of a specific enterocyte marker which is urinary intestinal fatty acid binding protein (I-FABP). Method: Maturation of the gut was studied in 60 premature babies(&lt;37 weeks of gestation) without gastrointestinal morbidity. 30 of them were exclusively breast-fed and the other 30 were formula-fed. Urinary I-FABP levels as the measure of gut maturation were measured at 7th, 12th, and 22 nd post-natal days. Results: In breast-fed babies, there was a statistically significant increase in urinary I-FABP levels between 7 th and 12 th days after birth compared with formula-fed babies (p&lt;0.01) Conclusions: The pattern of postnatal changes in urinary I-FABP levels suggests a delayed physiological response causing significantly delayed gut maturation in formula-fed babies compared with breast-fed ones.

A Pilot Study Evaluating Novel Urinary Biomarkers for Crohn’s Disease

Introduction: Although collecting faeces and blood samples are considered non-invasive methods of monitoring Crohn’s disease (CD), these methods are less preferred by some patients. This study utilized urine as an alternative to evaluate four disease biomarkers in young adults with active CD before and after exclusive enteral nutrition (EEN) therapy. Methods: Urine samples collected at baseline (W0) and after 8 weeks (W8) of EEN therapy were assayed by ELISA for levels of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3, and calprotectin. Levels of each biomarker were also compared with standard clinical parameters, including disease indexes, nutrient, and inflammatory markers. Results: Of the paired urine samples from 14 patients, 10 were female and 12 were newly diagnosed with CD. Urinary I-FABP:Cr (standardized to urine Cr) levels were significantly reduced, while urinary L-FABP:Cr levels increased following EEN therapy. Urinary L-FABP:Cr correlated positively with serum insulin-like growth factor 1 (IGF-1) (r = 0.60, p = 0.02). Urinary CLND3:Cr and calprotectin:Cr levels were not significantly different after treatment. Conclusion: I-FABP is a potential urinary biomarker of disease activity in adults with CD, while urinary L-FABP may be an indirect marker of nutritional status in adults with CD. CLND3 and calprotectin do not appear to have roles as urinary biomarkers in CD. These findings warrant further investigations using a larger sample size.

Predicting intestinal recovery after necrotizing enterocolitis in preterm infants.

Intestinal recovery after NEC is difficult to predict in individuals. We evaluated whether several biomarkers predict intestinal recovery after NEC in preterm infants. We measured intestinal tissue oxygen saturation (rintSO2) and collected urinary intestinal-fatty acidbinding protein (I-FABPu) levels 0-24 h and 24-48 h after NEC onset, and before and after the first re-feed. We assessed intestinal recovery in two ways: time to full enteral feeding (FEFt; below or equal/above group's median) and development of post-NEC complications (recurrent NEC/post-NEC stricture). We determined whether the rintSO2, its range, and I-FABPu differed between groups. We included 27 preterm infants who survived NEC (Bell's stage ≥ 2). Median FEFt was 14 [IQR: 12-23] days. Biomarkers only predicted intestinal recovery after the first re-feed. Mean rintSO2 ≥ 53% combined with mean rintSO2range ≥ 50% predicted FEFt < 14 days with OR 16.7 (CI: 2.3-122.2). The rintSO2range was smaller (33% vs. 51%, p < 0.01) and I-FABPu was higher (92.4 vs. 25.5 ng/mL, p = 0.03) in case of post-NEC stricture, but not different in case of recurrent NEC, compared with infants without complications. The rintSO2, its range, and I-FABPu after the first re-feed after NEC predicted intestinal recovery. These biomarkers have potential value in individualizing feeding regimens after NEC.

Calprotectin and Intestinal Fatty Acid Binding Protein (I-FABP) Level in Preterm Neonates with Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is inflammatory state of intestinal tissue which mostly occurred in preterm neonates and associated with ischemia and inflammation. This study was aimed to investigate calprotectin level (inflammatory marker) and intestinal fatty acid binding protein (I-FABP) (ischemia marker) in preterm neonates with NEC. This research was designed as cross sectional which involve 32 preterm neonates divided into 2 groups as follows: NEC group (n=16 subjects) and control group (n=16 subjects). Diagnosis of NEC was established by clinical and radiological signs (abdominal distension and pneumatosis). Fecal calprotectin and urinary I-FABP were measured using ELISA method. Results showed that fecal calprotectin and urinary I-FABP was significantly higher in NEC group as compared to control group ( Mann-Whitney test , p<0.05). Both calprotectin and I-FABP was positively correlated with NEC state (Spearman correlation test, p=0.000, r=0.866). Moreover, calprotectin and I-FABP level was positively correlated with grade (Bell’s classification) and type (Gordon’s classification) of NEC (Spearman correlation test, p<0.05). We concluded that calprotectin and I-FABP level was higher in NEC group. Moreover, I-FABP but not calprotectin, were correlated with grade and type of NEC.

The intestinal fatty acid-binding protein as a marker for intestinal damage in gastroschisis.

Background/PurposeWe analyzed the capacity of urinary Intestinal fatty acid-binding protein (I-FABP) to quantify the degree of mucosal injury in neonates with gastroschisis (GS) and to predict the speed of their clinical recovery after surgery.MethodsIn this prospective study, we collected urine during the first 48h after surgery from neonates operated between 2012 and 2015 for GS. Neonates with surgery that did not include gut mucosa served as controls for simple GS and neonates with surgery for intestinal atresia served as control for complex GS patients. The I-FABP levels were analyzed by ELISA.ResultsUrinary I-FABP after the surgery is significantly higher in GS newborns than in control group; I-FABP in complex GS is higher than in simple GS. I-FABP can predict subsequent operation for ileus in patients with complex GS. Both ways of abdominal wall closure (i.e. primary closure and stepwise reconstruction) led to similar levels of I-FABP. None of the static I-FABP values was useful for the outcome prediction. The steep decrease in I-FABP after the surgery is associated with faster recovery, but it cannot predict early start of minimal enteral feeding, full enteral feeding or length of hospitalization.ConclusionUrinary I-FABP reflects the mucosal damage in gastroschisis but it has only a limited predictive value for patients’ outcome.

Bowel Ischemia in ICU Patients: Diagnostic Value of I-FABP Depends on the Interval to the Triggering Event.

Background Intestinal fatty acid-binding protein (I-FABP) has been shown to be of high diagnostic value in patients with acute mesenteric ischemia. Whether these results can be reproduced in critically ill patients on the ICU was to be investigated. Materials and Methods I-FABP was measured in serum and urine of 43 critically ill patients in ICU when mesenteric ischemia was suspected. Bowel ischemia was confirmed in 21 patients (group 1). 22 patients who survived at least seven days without confirmation of ischemia were assigned to group 2. I-FABP levels were compared between the groups, and interval from the event that has triggered ischemia to I-FABP measurement was recorded. Results For the identification of patients with mesenteric ischemia, sensitivity, specificity, and area under the curve (AUC) for serum and urine I-FABP were 33.3%, 95.5%, and 0.565 and 81.3%, 70.0%, and 0.694, respectively. I-FABP measurements performed within 12 to 48 h after the event that triggered ischemia showed a sensitivity, specificity, and AUC for serum and urine of 75%, 100%, and 0.853 and 100%, 73.3%, and 0.856, respectively. Conclusions In ICU patients, one single I-FABP measurement at the time of clinical suspicion failed to reliably detect or exclude mesenteric ischemia. A higher diagnostic value of I-FABP was only confirmed in the early stages of mesenteric ischemia. I-FABP may be used most appropriately in perioperative monitoring.

Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients

BackgroundAcute mesenteric ischemia (AMI) has a high morbidity and mortality and often presents as a diagnostic challenge. Currently, there is no blood, urine, or radiologic tests that provide a definitive diagnosis of AMI. The aim of this study was to evaluate the clinical accuracy of urine intestinal fatty acid-binding protein (I-FABP) to diagnosis AMI. Materials and methodsTwenty patients referred to the Acute Care Surgery service at University of Alberta Hospital with suspected AMI taken to the operating room for definitive diagnosis were recruited. Pathologic findings from surgical specimens confirmed a gold standard diagnosis for intestinal ischemia. The patients found to be nonischemic became the internal controls. Conventional clinical markers were examined in blood including white blood cell count, lactate, and creatinine. Blood was also examined by enzyme-linked immunosorbent assays (ELISAs) for I-FABP and interleukin-6. Urine was examined preoperatively and 6 and 24 h postoperatively for I-FABP. ResultsThirteen patients were pathologically diagnosed with AMI while five patients were nonischemic; two were excluded due to missing biologic specimens. There was no difference in age or gender between ischemic and nonischemic patients (56 ± 5 versus 66 ± 11 years old, respectively; six females with ischemic and three females in the nonischemic group). There was no difference in serum lactate and creatinine between the two groups. Serum interleukin-6 levels in patients with AMI were significantly higher than nonischemic controls (0.4 ± 0.2 ng/mL versus 0.2 ± 0.07 ng/mL, respectively, P = 0.03). There was a nonstatistically significant increase in serum I-FABP in AMI patients compared to internal controls (9 ± 3 ng/mL versus 2.4 ± 0.9 ng/mL, respectively, P = 0.2). Urine I-FABP was significantly higher in patients diagnosed with AMI than in controls (7 ± 1 ng/mL versus 2 ± 1 ng/mL, respectively, P = 0.007). The receiver operating characteristic curve illustrated that urine I-FABP discriminates significantly between patients with AMI and controls (area under receiver operating characteristic = 0.88, P = 0.03). ConclusionsThe traditional clinical markers lactate and white blood cell count were not able to differentiate AMI from nonischemic bowel. However, we found that urine I-FABP was a noninvasive biomarker with high specificity and sensitivity for accurately diagnosing AMI in patients. A noninvasive accurate tool for AMI would facilitate for a rapid treatment, while preventing unnecessary surgical interventions in high-risk patient populations.