The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery

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Passov , A , Petäjä , L , Pihlajoki , M , Salminen , U-S , Suojaranta , R , Vento , A , Andersson , S , Pettilä , V , Schramko , A & Pesonen , E 2019 , ' The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery ' , BMC Nephrology , vol. 20 , 182 . https://doi.org/10.1186/s12882-019-1380-4

Title: The origin of plasma neutrophil gelatinase-associated lipocalin in cardiac surgery
Author: Passov, Arie; Petäjä, Liisa; Pihlajoki, Marjut; Salminen, Ulla-Stina; Suojaranta, Raili; Vento, Antti; Andersson, Sture; Pettilä, Ville; Schramko, Alexey; Pesonen, Eero
Contributor: University of Helsinki, HUS Perioperative, Intensive Care and Pain Medicine
University of Helsinki, Anestesiologian yksikkö
University of Helsinki, Children's Hospital
University of Helsinki, Department of Surgery
University of Helsinki, Department of Diagnostics and Therapeutics
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Children's Hospital
University of Helsinki, HUS Perioperative, Intensive Care and Pain Medicine
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2019-05-22
Language: eng
Number of pages: 10
Belongs to series: BMC Nephrology
ISSN: 1471-2369
URI: http://hdl.handle.net/10138/303712
Abstract: Background: Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery. Methods: Two separate patient cohorts were studied: 1) the "kinetic cohort" (n = 29) and 2) the "FINNAKI cohort" (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the "FINNAKI cohort" Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson's and Spearman's tests were used as appropriate. Results: There was strong intraoperative association between NGAL and lactoferrin at all four time-points in the "kinetic cohort". In the "FINNAKI cohort", NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p <0.001) and at admission to the intensive care unit (R = 0.69, p <0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p <0.001; lactoferrin: p <0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3-53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0-64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 - 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients. Conclusions: Plasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.
Subject: Neutrophil gelatinase-associated lipocalin (NGAL)
Cardiac surgery-associated acute kidney injury
Acute kidney injury
Neutrophil activation
Biomarkers
ACUTE KIDNEY INJURY
PROTEIN
NGAL
IDENTIFICATION
TRANSCRIPTOME
LACTOFERRIN
ACTIVATION
BIOMARKER
GRANULES
IMPACT
3126 Surgery, anesthesiology, intensive care, radiology
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