The Utility of Serum Hepcidin as a Biomarker for Late-Onset Neonatal Sepsis

Wu, Tai-Wei; Tabangin, Meredith E.; Kusano, Ryosuke; Ma, Yan; Ridsdale, Ross; Akinbi, Henry T.

doi:10.1016/j.jpeds.2012.06.010

Cited by 64 publications

(45 citation statements)

References 23 publications

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“…Similarly, Wu et al [13] also reported higher postnatal hepcidin concentrations in preterm infants. As all of the above mentioned hepcidin concentrations were determined using the same ELISA, we hypothesize that these differences between cord blood and postnatal values are real and likely reflect the impact of inflammatory conditions, as well as of iron supplementation, blood transfusion and phlebotomy practice.…”

Section: Discussionmentioning

confidence: 80%

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Gestational Age-Specific Reference Ranges of Hepcidin in Cord Blood

Lorenz¹,

Herbst²,

Engel

et al. 2014

Neonatology

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Background: Iron deficiency (ID) contributes to anaemia of prematurity, and hence the reliable assessment of iron nutrition status appears to be mandatory. Objective: To establish gestational age (GA)-specific reference ranges for hepcidin concentrations in cord blood [Hep_(CB)] of preterm and term infants and to identify pre- and perinatal confounding factors. Methods: This is a prospective observational study including 221 infants (GA at birth: 24-42 weeks). Hep_(CB) along with complete blood counts, ferritin and parameters of inflammation and clinical data were recorded. Data are presented as medians (IQR). Results: The Hep_(CB) of very preterm infants (GA <30 weeks, n = 40) was 26.9 ng/ml (13.5-63.1), for moderately preterm infants (GA 30-36 weeks, n = 81) it was 45.9 ng/ml (24.7-74.5) and for term infants (GA ≥37 weeks, n = 100) it was 103.9 ng/ml (61.4-149.2). The Hep_(CB) of infants with ID was lower [36.9 ng/ml (18.0-58.3)] than that of iron-replete infants [86.6 ng/ml (51.9-143.8)]. The Hep_(CB) of infants delivered by elective caesarean section was lower [38.3 ng/ml (15.5-73.7)] than that of infants after spontaneous vaginal delivery or secondary caesarean section [80.3 ng/ml (48.5-137.6)]. Infants with a standard deviation score for birth weight (SDS_BW) <-2 had a lower Hep_(CB) [23.1 ng/ml (11.7-61.5)] compared to infants with SDS_BW ≥-2 [71.1 ng/ml (34.0-121.7)]. The highest Hep_(CB) (437.6 ng/ml) was recorded in an infant with Enterococcus faecalis sepsis. Multiple logistic regression analysis confirmed ferritin, GA and mode of delivery as important factors associated with Hep_(CB). Conclusion: This is the first report on GA-specific reference ranges for Hep_(CB) in preterm infants. Whereas iron stores, GA and mode of delivery were associated with Hep_(CB), the association with inflammation and intra-uterine growth retardation was less clear.

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Section: Discussionmentioning

confidence: 80%

“…Likewise, in preterm infants with late-onset culture-proven sepsis, hepcidin was higher than in non-septic infants [13]. However, there was no correlation between Hep (CB) and IL-6 and CRP, possibly due to the fact that the kinetics of IL-6, CRP and hepcidin are different.…”

Section: Discussionmentioning

confidence: 99%

Gestational Age-Specific Reference Ranges of Hepcidin in Cord Blood

Lorenz¹,

Herbst²,

Engel

et al. 2014

Neonatology

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“…In addition, HEPC levels have been found to be elevated in anemic patients with chronic inflammation, chronic kidney disease or cancer. HEPC expression is, therefore, considered a potentially good marker of anemia or inflammation (van Eijk et al 2011; Wu et al 2012). In patients with lupus nephritis, changes in urine HEPC-20 and -25 measures predicted renal flares (Zhang et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…HEPC, other than being a highly conserved antimicrobial bdefensin-like peptide, has a dual role in innate immunity: it enhances intracellular sequestration of iron by degrading the membrane iron transporter ferroportin (thereby depriving pathogens of this essential mineral) and it has direct antimicrobial activity against bacteria and viruses (Prowle et al 2011;Wu et al 2012;Zeng et al 2015). This could help explain the significant elevations in serum HEPC in septic AKI patients, i.e.…”

Section: Discussionmentioning

confidence: 99%

Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

Schaalan

Mohamed

2016

Journal of Immunotoxicology

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The antimicrobial b-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1a, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/ creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFa (4.4-times) and TGFb1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1a levels were also increased (8.8-and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFa and TGFb1 (25.5% and 26.2%, respectively), HEPC and HIF-1a levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFa and TGFb1 and serum HIF-1a and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1a are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia-related complications.ARTICLE HISTORY

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“…Unlike our study, they did not compare hepcidin with other sepsis markers. Wu et al (13) observed that hepcidin level was four times greater in 17 newborns with late-onset neonatal sepsis compared to healthy controls. Similarly, in this study, the sensitivity and specificity of hepcidin for a diagnosis of sepsis were found to be higher than that of CRP.…”

Section: Discussionmentioning

confidence: 98%

Role of hepcidin in the diagnosis of sepsis and septic shock in children

2018

Turk J Med Sci

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The Utility of Serum Hepcidin as a Biomarker for Late-Onset Neonatal Sepsis

Cited by 64 publications

References 23 publications

Gestational Age-Specific Reference Ranges of Hepcidin in Cord Blood

Gestational Age-Specific Reference Ranges of Hepcidin in Cord Blood

Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

Role of hepcidin in the diagnosis of sepsis and septic shock in children

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