Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Promising Biomarker for Late Onset Culture-Positive Sepsis in Very Low Birth Weight Infants

Abstract

Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for Ն7 d and Ͻ7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p Ͻ 0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p Ͻ 0.05 to Ͻ0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants. (Pediatr Res 67: 636-640, 2010)

Assessment of renal functional maturation and injury in preterm neonates during the first month of life

“…NGAL is excreted by renal proximal tubule cells as a response to AKI (41); however, NGAL is produced during nephrogenesis (16), and levels may also be raised in late-onset sepsis (34). Although positive findings have been reported among older infants (57), the usefulness of urinary NGAL as a marker of AKI in preterm neonates remains unclear (20,23,33,34).…”

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

“…However, we have previously described the longitudinal behavior of UNGAL in very-low-birth-weight infants with sepsis (14): UNGAL increases from baseline 1 d prior to blood culture sampling and peaks at a mean level six times higher than baseline 2 d after the initiation of the antibiotic treatment, which then begins a slow descent back toward baseline that encompasses the duration of treatment. This pattern suggests that additional UNGAL determinations obtained serially, early in the course of a sepsis evaluation, might enhance the sensitivity and PPV of the biomarker.…”

“…UNGAL is an indicator of acute kidney injury (AKI) due to sepsis, ischemia, and nephrotoxins (5,6); concentrations have been shown to rise after cardiopulmonary bypass and renal transplantation in adults and children (7-10), with contrast administration (11), with hemolytic-uremic syndrome (12), and with lupus nephritis (13). We have previously demonstrated, in a pilot study, that concentrations of UNGAL in urine specimens obtained at the time of sepsis evaluations in very-low-birth-weight infants correlated with the presence of sepsis (14).The objective of this study was to prospectively measure UNGAL at the time of initial evaluation for late-onset sepsis among infants in a quaternary care NICU to determine a cutoff concentration of UNGAL for culture-positive lateonset sepsis with optimal sensitivity and NPV compared with negative-sepsis evaluations. We hypothesized that (i) UNGAL concentrations would be increased in neonates of all GAs and birth weights (BWs) with culture-positive lateonset sepsis and (ii) UNGAL would have a sensitivity and NPV comparable to those of CRP at the time of the sepsis workup.…”

“…UNGAL is an indicator of acute kidney injury (AKI) due to sepsis, ischemia, and nephrotoxins (5,6); concentrations have been shown to rise after cardiopulmonary bypass and renal transplantation in adults and children (7)(8)(9)(10), with contrast administration (11), with hemolytic-uremic syndrome (12), and with lupus nephritis (13). We have previously demonstrated, in a pilot study, that concentrations of UNGAL in urine specimens obtained at the time of sepsis evaluations in very-low-birth-weight infants correlated with the presence of sepsis (14).…”

Effects of Preterm Birth on the Kidney

“…In the preterm neonate, a small number of studies have been conducted for the assessment of urinary NGAL levels, with mixed results. These studies have shown that the highest NGAL levels are evident in the neonates that are critically ill, with and without evidence of renal dysfunction (Lavery et al, 2008;Parravicini, 2010); in particular, NGAL shows potential as a promising biomarker of late-onset sepsis (Lavery et al, 2008;Parravicini et al, 2010). Urinary NGAL levels also strongly correlated with gestational and postnatal age (Lavery et al, 2008;Huynh et al, 2009), perhaps reflecting the renal production of NGAL during nephrogenesis (Gwira et al, 2005) which is often still ongoing during the early postnatal period.…”