Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis

Abstract

Background:To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. Methods: This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. results: The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. conclusion: UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.l ate-onset sepsis, by definition, occurs at >72 h of life and can affect as many as 20-30% of infants hospitalized in the neonatal intensive care unit (NICU), with varying mortality rates depending on gestational age (GA) (1,2). Accurate diagnosis of late-onset sepsis in this vulnerable population can be difficult due to nonspecific signs and symptoms, as well as due to difficulties in obtaining sufficient diagnostic specimens, such as an adequate volume of blood samples. In order to determine which infants are most likely to be infected, biomarkers have been utilized with varying success. The ideal biomarker should have rapid onset of expression, reversibility of expression when the disease abates, ease of collection and measurement, high sensitivity, and high negative predictive value (NPV). Currently, C-reactive protein (CRP) is the most frequently used serum biomarker in the NICU population. As described by Benitz et al. (3), a single CRP at the time of a sepsis evaluation has a modest sensitivity (65%) and NPV (79%). In septic infants, CRP peaks 24-48 h after the onset of symptoms; a second sample obtained during this time period increases the sensitivity to 97%. Although CRP can help determine which neonates may not be septic, it is a relatively invasive, late biomarker and the results of the second sample may have limited additional diagnostic utility compared with blood culture results, which are often available about the same time. A noninvasive biomarker with high sensitivity, high NPV, and results available at the time of sepsis evalu...

Clinical effect of combined ulinastatin and continuous renal replacement therapy on management of severe sepsis with acute kidney injury

“…Sepsis patients have changes in their neuroendocrine system such as activation of sympathetic nervous system, release of vasopressin, and activation of renin -angiotensin -aldosterone system. These changes can result in decrease in renal blood flow, renal tubular epithelial cell necrosis and decline in renal function [13].…”

The Measurement of Neutrophil Gelatinase Associated Lipocalin In Umbilical Cord Blood And The Assessment Of Its Relationship With Neonatal Results

“…Sepsis is one of the major causes of AKI in neonates. In a study conducted by Pynn et al (18) , urine NGAL was pointed out as a non-invasive biomarker with high negative predictive value at the time of late-onset sepsis assessment in neonates. According to a study conducted by Parravicini et al (4) , on 91 very low birth weight infants, urine NGAL is a promising candidate as an early biomarker for sepsis and it was also shown that urinary NGAL levels was an early biomarker to detect sepsis.…”

“…In our study, there was no statistically significant difference between the risk factors of sepsis, such as male gender, gestational age below 37 weeks and umbilical cord blood NGAL levels; however, there was a statistically significant difference between PROM, which is also a risk factor in sepsis, and umbilical cord blood NGAL levels. (18) In a group of neonates with intrauterine hypoxia, Essajee et al (20) found that urine NGAL is a predictor of mortality and hypoxic encephalopathy. Similar results were found in another study conducted by Fiala et al (21) .…”

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass

“…In children, uNGAL's ability to predict AKI is enhanced when it is used in combination with other biomarkers for renal injury or function such as interleukin-18 (IL-18), Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1) [29,31]. We examined only the association of uNGAL and AKI, as this study was part of a series of studies examining the utility of uNGAL as a biomarker for various outcomes [19,22,43,44]; however, further investigation of the utility of multiple biomarkers in this population is warranted. Finally, while to the best of our knowledge neonates included in our study had normal renal anatomy and function, there may be microscopic changes that could not be appreciated by ultrasound.…”