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Neutrophil gelatinase-associated lipocalin (NGAL) is a poor diagnostic marker for sepsis in the ICU – An observational multicentre study

Boström, Lisa LU ; Hagström, Sofie ; Engström, Jonas LU orcid ; Larsson, Anders ; Friberg, Hans LU ; Lengquist, Maria LU orcid and Frigyesi, Attila LU (2026) In PLOS ONE 21(8). p.1-16
Abstract
Background
Sepsis is a major public health challenge, and reliable biomarkers are essential for distinguishing sepsis from other conditions. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has shown promise as a diagnostic marker due to its role in the immune response. This study evaluates plasma NGAL as a diagnostic tool at the time of ICU admission.

Methods
We analysed plasma NGAL and C-reactive protein (CRP) levels in 2950 adult patients admitted to four ICUs between 2015 and 2018. All patients were retrospectively screened for Sepsis-3 criteria at ICU admission. The discriminative performance of NGAL and CRP for sepsis was assessed using receiver operating characteristic (ROC) analysis, with NGAL levels adjusted for... (More)
Background
Sepsis is a major public health challenge, and reliable biomarkers are essential for distinguishing sepsis from other conditions. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has shown promise as a diagnostic marker due to its role in the immune response. This study evaluates plasma NGAL as a diagnostic tool at the time of ICU admission.

Methods
We analysed plasma NGAL and C-reactive protein (CRP) levels in 2950 adult patients admitted to four ICUs between 2015 and 2018. All patients were retrospectively screened for Sepsis-3 criteria at ICU admission. The discriminative performance of NGAL and CRP for sepsis was assessed using receiver operating characteristic (ROC) analysis, with NGAL levels adjusted for chronic kidney disease (CKD) and age. Patients were stratified by renal function.

Findings
Plasma NGAL levels were significantly higher in septic patients (p < 0.001). For the whole cohort, NGAL alone yielded an area under the curve (AUC) of 0.66 (confidence interval (CI) 0.64–0.68), CRP yielded an AUC of 0.71 (CI 0.69–0.73, p < 0.001), and combining NGAL with CRP nominally improved discriminative performance (AUC 0.018, 95% CI 0.011–0.027). Stratified analyses indicated that NGAL, together with CRP, significantly outperformed CRP alone in patients with no kidney injury and those with Acute Kidney Injury (AKI) only. In contrast, differences were not significant in patients with CKD only or CKD and AKI.

Conclusion
In this large cohort, NGAL showed modest discrimination for sepsis, with a nominal improvement when combined with CRP. These findings do not indicate that NGAL meaningfully improves sepsis diagnosis in the ICU. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLOS ONE
volume
21
issue
8
article number
e0343752
pages
1 - 16
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:42599955
  • scopus:105047529917
ISSN
1932-6203
DOI
10.1371/journal.pone.0343752
language
English
LU publication?
yes
id
72a89d97-2fbb-445d-a06c-d0a50cf0fd61
date added to LUP
2026-09-13 14:36:20
date last changed
2026-09-14 07:49:23
@article{72a89d97-2fbb-445d-a06c-d0a50cf0fd61,
  abstract     = {{Background<br/>Sepsis is a major public health challenge, and reliable biomarkers are essential for distinguishing sepsis from other conditions. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has shown promise as a diagnostic marker due to its role in the immune response. This study evaluates plasma NGAL as a diagnostic tool at the time of ICU admission.<br/><br/>Methods<br/>We analysed plasma NGAL and C-reactive protein (CRP) levels in 2950 adult patients admitted to four ICUs between 2015 and 2018. All patients were retrospectively screened for Sepsis-3 criteria at ICU admission. The discriminative performance of NGAL and CRP for sepsis was assessed using receiver operating characteristic (ROC) analysis, with NGAL levels adjusted for chronic kidney disease (CKD) and age. Patients were stratified by renal function.<br/><br/>Findings<br/>Plasma NGAL levels were significantly higher in septic patients (p &lt; 0.001). For the whole cohort, NGAL alone yielded an area under the curve (AUC) of 0.66 (confidence interval (CI) 0.64–0.68), CRP yielded an AUC of 0.71 (CI 0.69–0.73, p &lt; 0.001), and combining NGAL with CRP nominally improved discriminative performance (AUC 0.018, 95% CI 0.011–0.027). Stratified analyses indicated that NGAL, together with CRP, significantly outperformed CRP alone in patients with no kidney injury and those with Acute Kidney Injury (AKI) only. In contrast, differences were not significant in patients with CKD only or CKD and AKI.<br/><br/>Conclusion<br/>In this large cohort, NGAL showed modest discrimination for sepsis, with a nominal improvement when combined with CRP. These findings do not indicate that NGAL meaningfully improves sepsis diagnosis in the ICU.}},
  author       = {{Boström, Lisa and Hagström, Sofie and Engström, Jonas and Larsson, Anders and Friberg, Hans and Lengquist, Maria and Frigyesi, Attila}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{1--16}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLOS ONE}},
  title        = {{Neutrophil gelatinase-associated lipocalin (NGAL) is a poor diagnostic marker for sepsis in the ICU – An observational multicentre study}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0343752}},
  doi          = {{10.1371/journal.pone.0343752}},
  volume       = {{21}},
  year         = {{2026}},
}