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

BMC Nephrology

Sture Andersson¹  Marjut Pihlajoki¹  Raili Suojaranta²  Antti Vento²  Ulla-Stina Salminen²  Alexey Schramko³  Arie Passov³  Eero Pesonen³  Liisa Petäjä³  Ville Pettilä⁴ 

[1] 0000 0004 0410 2071, grid.7737.4, Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, PO BOX 347, Stenbäckinkatu 9, FIN 00029 HUS, Helsinki, Finland;0000 0004 0410 2071, grid.7737.4, Department of Cardiac Surgery, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, PO BOX 340, Haartmaninkatu 4, FIN 00029 HUS, Helsinki, Finland;0000 0004 0410 2071, grid.7737.4, Division of Anaesthesiology, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, PO BOX 340, Haartmaninkatu 4, FIN 00029 HUS, Helsinki, Finland;0000 0004 0410 2071, grid.7737.4, Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, PO BOX 340, Haartmaninkatu 4, FIN 00029 HUS, Helsinki, Finland;

关键词: Neutrophil gelatinase-associated lipocalin (NGAL);    Cardiac surgery-associated acute kidney injury;    Acute kidney injury;    Neutrophil activation;    Biomarkers;   

DOI  :  10.1186/s12882-019-1380-4

来源: publisher

【 摘 要 】

BackgroundAcute 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.MethodsTwo 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.ResultsThere 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.ConclusionsPlasma 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.

【 授权许可】

CC BY