Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients

Abstract The early identification of sepsis in surgical intensive care patients is challenging due to the physiological postoperative alterations of vital signs and inflammatory biomarkers. Soluble Delta-like protein 1 (sDLL1) may be a potential discriminatory biomarker for this purpose. For this re...

Full description

Bibliographic Details
Main Authors: Emmanuel Schneck, Fabian Edinger, Florian Uhle, Melanie Markmann, Andreas Hecker, Markus A. Weigand, Michael Sander, Christian Koch
Format: Article
Language:English
Published: Nature Portfolio 2022-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-17778-9
_version_ 1798038055813120000
author Emmanuel Schneck
Fabian Edinger
Florian Uhle
Melanie Markmann
Andreas Hecker
Markus A. Weigand
Michael Sander
Christian Koch
author_facet Emmanuel Schneck
Fabian Edinger
Florian Uhle
Melanie Markmann
Andreas Hecker
Markus A. Weigand
Michael Sander
Christian Koch
author_sort Emmanuel Schneck
collection DOAJ
description Abstract The early identification of sepsis in surgical intensive care patients is challenging due to the physiological postoperative alterations of vital signs and inflammatory biomarkers. Soluble Delta-like protein 1 (sDLL1) may be a potential discriminatory biomarker for this purpose. For this reason, this study aimed to evaluate sDLL1 for the identification of sepsis in a cohort of surgical intensive care patients. This study comprises a secondary analysis of a prospective observational study including 80 consecutive patients. The study groups included 20 septic shock patients, 20 patients each undergoing major abdominal surgery (MAS) and cardiac artery bypass surgery (CABG), and 20 matched control subjects (CTRL). The surveillance period was 72 h. The plasma concentration of sDLL1 was measured with ELISA. The plasma levels of sDLL1 were significantly elevated in septic patients compared to both surgical cohorts (septic vs. all postoperative time points, data are shown as median and interquartile range [IQR]; septic shock: 17,363 [12,053–27,299] ng/mL, CABG 10,904 [8692–16,250] ng/mL; MAS 6485 [4615–9068] ng/mL; CTRL 5751 [3743–7109] ng/mL; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p < 0.001). ROC analysis showed a sufficient prediction of sepsis with limited specificity (AUCROC 0.82 [0.75–0.82], sensitivity 84%, specificity 68%). The plasma levels of sDLL correlated closely with renal parameters (creatinine: correlation coefficient = 0.60, r 2 = 0.37, p < 0.0001; urea: correlation coefficient = 0.52, r 2 = 0.26, p < 0.0001), resulting in a good predictive performance of sDLL1 for the identification of acute kidney injury (AKI; AUCROC 0.9 [0.82–0.9], sensitivity 83%, specificity 91%). By quantifying the plasma concentration of sDLL1, sepsis can be discriminated from the physiological postsurgical inflammatory response in abdominal and cardiac surgical patients. However, sDLL1 has only limited specificity for the detection of sepsis in cardiac surgical patients, which may be explained by impaired renal function. Based on these findings, this study identifies the predictive value of sDLL1 for the detection of AKI, making it a potential biomarker for surgical intensive care patients. Trial registration DRKS00013584, Internet Portal of the German Clinical Trials Register (DRKS), registration date 11.07.2018, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013584 .
first_indexed 2024-04-11T21:35:00Z
format Article
id doaj.art-8b35466365f6455c99e08499058e2077
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-11T21:35:00Z
publishDate 2022-08-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-8b35466365f6455c99e08499058e20772022-12-22T04:01:47ZengNature PortfolioScientific Reports2045-23222022-08-011211910.1038/s41598-022-17778-9Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patientsEmmanuel Schneck0Fabian Edinger1Florian Uhle2Melanie Markmann3Andreas Hecker4Markus A. Weigand5Michael Sander6Christian Koch7Department of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and MarburgDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and MarburgDepartment of Anesthesiology, Heidelberg University HospitalDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and MarburgDepartment of General and Thoracic Surgery, University Hospital of Giessen and MarburgDepartment of Anesthesiology, Heidelberg University HospitalDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and MarburgDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and MarburgAbstract The early identification of sepsis in surgical intensive care patients is challenging due to the physiological postoperative alterations of vital signs and inflammatory biomarkers. Soluble Delta-like protein 1 (sDLL1) may be a potential discriminatory biomarker for this purpose. For this reason, this study aimed to evaluate sDLL1 for the identification of sepsis in a cohort of surgical intensive care patients. This study comprises a secondary analysis of a prospective observational study including 80 consecutive patients. The study groups included 20 septic shock patients, 20 patients each undergoing major abdominal surgery (MAS) and cardiac artery bypass surgery (CABG), and 20 matched control subjects (CTRL). The surveillance period was 72 h. The plasma concentration of sDLL1 was measured with ELISA. The plasma levels of sDLL1 were significantly elevated in septic patients compared to both surgical cohorts (septic vs. all postoperative time points, data are shown as median and interquartile range [IQR]; septic shock: 17,363 [12,053–27,299] ng/mL, CABG 10,904 [8692–16,250] ng/mL; MAS 6485 [4615–9068] ng/mL; CTRL 5751 [3743–7109] ng/mL; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p < 0.001). ROC analysis showed a sufficient prediction of sepsis with limited specificity (AUCROC 0.82 [0.75–0.82], sensitivity 84%, specificity 68%). The plasma levels of sDLL correlated closely with renal parameters (creatinine: correlation coefficient = 0.60, r 2 = 0.37, p < 0.0001; urea: correlation coefficient = 0.52, r 2 = 0.26, p < 0.0001), resulting in a good predictive performance of sDLL1 for the identification of acute kidney injury (AKI; AUCROC 0.9 [0.82–0.9], sensitivity 83%, specificity 91%). By quantifying the plasma concentration of sDLL1, sepsis can be discriminated from the physiological postsurgical inflammatory response in abdominal and cardiac surgical patients. However, sDLL1 has only limited specificity for the detection of sepsis in cardiac surgical patients, which may be explained by impaired renal function. Based on these findings, this study identifies the predictive value of sDLL1 for the detection of AKI, making it a potential biomarker for surgical intensive care patients. Trial registration DRKS00013584, Internet Portal of the German Clinical Trials Register (DRKS), registration date 11.07.2018, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013584 .https://doi.org/10.1038/s41598-022-17778-9
spellingShingle Emmanuel Schneck
Fabian Edinger
Florian Uhle
Melanie Markmann
Andreas Hecker
Markus A. Weigand
Michael Sander
Christian Koch
Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
Scientific Reports
title Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
title_full Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
title_fullStr Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
title_full_unstemmed Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
title_short Delta-like canonical Notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
title_sort delta like canonical notch ligand 1 is predictive for sepsis and acute kidney injury in surgical intensive care patients
url https://doi.org/10.1038/s41598-022-17778-9
work_keys_str_mv AT emmanuelschneck deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT fabianedinger deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT florianuhle deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT melaniemarkmann deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT andreashecker deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT markusaweigand deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT michaelsander deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients
AT christiankoch deltalikecanonicalnotchligand1ispredictiveforsepsisandacutekidneyinjuryinsurgicalintensivecarepatients