Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease

Abstract

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting mainly preterm newborns. It is characterized by unexpected onset and rapid progression with specific diagnostic signs as pneumatosis intestinalis or gas in the portal vein appearing later in the course of the disease. Therefore, we analyzed diagnostic and prognostic potential of the markers of early NEC pathogenesis, such as excessive inflammatory response (serum amyloid A (SAA)) and gut epithelium damage (intestinal and liver fatty acid-binding protein (I-FABP and L-FABP, respectively) and trefoil factor-3 (TFF-3)). We used ELISA to analyze these biomarkers in the urine of patients with suspected NEC, either spontaneous or surgery-related, or in infants without gut surgery (controls). Next, we compared their levels with the type of the disease (NEC or sepsis) and its severity. Already at the time of NEC suspicion, infants who developed NEC had significantly higher levels of all tested biomarkers than controls and higher levels of I-FABP and L-FABP than those who will later develop sepsis. Infants who will develop surgery-related NEC had higher levels of I-FABP and L-FABP than those who will develop sepsis already during the first 6 hours after the abdominal surgery. I-FABP was able to discriminate between infants who will develop NEC or sepsis and the SAA was able to discriminate between medical and surgical NEC. Moreover, the combination of TFF-3 with I-FABP and SAA could predict pneumatosis intestinalis, and the combination of I-FABP, L-FABP, and SAA could predict gas in the portal vein or long-term hospitalization and low SAA predicts early full enteral feeding. Thus, these biomarkers may be useful not only in the early, noninvasive diagnostics but also in the subsequent NEC management.

Urinary liver-type fatty acid-binding protein variation as a predictive value of short-term mortality in intensive care unit patients

“…Contrary to our previous findings, Doi et al reported an association between urinary L-FABP and 14-day mortality, in addition to the onset of AKI [5]. L-FABP was originally discovered as a specific marker for AKI; however, in recent years, it has been reported that urinary L-FABP increases due to damage to various other organs or surgical invasion [6][7][8][9][10][11][12][13][14], and therefore, it has also emerged as a marker of general organ damage.…”

Intestinal fatty acid-binding protein, a biomarker of intestinal barrier dysfunction, increases with the progression of type 2 diabetes

“…I-FABP is an intracellular protein specifically and abundantly expressed in intestinal epithelial cells, and its increased serum concentration represents intestinal epithelial cell damage and IB dysfunction ( Gajda & Storch, 2015 ; Wells et al, 2017 ). As a biomarker of IB dysfunction, I-FABP determination has been used in patients with necrotizing enterocolitis ( Coufal et al, 2020 ), acute mesenteric ischemia ( Salim et al, 2017 ), strangulated small bowel obstruction ( Kittaka et al, 2014 ), Crohn’s disease ( Sarikaya et al, 2015 ), blunt trauma ( Matsumoto et al, 2017 ), celiac disease ( Oldenburger et al, 2018 ), acute pancreatitis( Kupcinskas et al, 2018 ; Goswami et al, 2017 ), acute decompensated heart failure ( Kitai et al, 2017 ), chronic renal failure ( Okada et al, 2018 ), septic shock ( Sekino et al, 2017 ), psoriasis ( Sikora et al, 2019 ), and even physiological stressor-induced intestinal damage ( March et al, 2017 ). In addition to serum I-FABP, many other biomarkers are used to measure IB function ( Wells et al, 2017 ; Piton & Capellier, 2016 ).…”

Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage via Akt signaling

“…For critically ill children, where the body is in a stressed state, serum ITF concentration is associated with gastrointestinal failure and prognosis[ 20 ]. Another study has suggested that urinary ITF can help diagnose and predict the disease course in necrotizing enterocolitis at the early stage in newborns[ 21 ]. Previous studies have also paid close attention to the application of ITF to inflammatory bowel disease, showing that ITF could be used as a biomarker to predict disease activity and assess mucosal healing in ulcerative colitis[ 22 , 23 ].…”