The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase–Associated Lipocalin in Pediatric Heart Surgery*

Pesonen, Eero; Suominen, Pertti; Keski‐Nisula, Juho; Mattila, Ilkka; Rautiainen, Paula; Jahnukainen, Timo

doi:10.1097/pcc.0000000000000573

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…This effect of on-pump surgery has also been demonstrated before [37]. Third, peri-operative methylprednisolone reduced plasma NGAL and LF similarly in pediatric cardiac surgery [38]. The latter is consistent with the fact that corticosteroids have been demonstrated to directly inhibit neutrophils [39].…”

Section: Discussionsupporting

confidence: 76%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 76%

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

et al. 2019

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“…Neutrophil gelatinase-associated lipocalin appears to come from active neutrophils to a large extent. When interpreting plasma neutrophil gelatinaseassociated lipocalin levels as a kidney damage marker in pediatric heart surgery, preoperative methylprednisolone can be a confusing factor [35]. After neonatal cardiopulmonary bypass surgery, prophylactic postoperative hydrocortisone lowers low cardiac output syndrome, improves fluid balance and urine output, and minimizes inflammation [39].…”

Section: Discussionmentioning

confidence: 99%

Cardiac surgery-associated acute kidney injury in newborns: A meta-analysis

et al. 2023

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Introduction: Acute kidney injury is a common complication following pediatric heart surgery, and it has been linked to an increased risk of morbidity and fatality. Methods: The PubMed and Medline databases were combed for relevant research until May 2022. The terms [Cardiac surgery] AND [acute renal injury] AND [newborns OR children OR neonates] AND [randomized control studies OR randomized control trials] were used as search criteria. The studies that met the inclusion criteria were considered qualified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total of 2,941 newborns or children were enrolled in 14 studies, with 931 developing acute renal damage. 2,095 of the enrolled infants and children received steroid, aminophylline, dexmedetomidine, and acetaminophen therapies. In seven studies, the odds ratio for steroids was not significantly different from control. In contrast, two studies comparing aminophylline to a control group found no statistically significant change. Two studies found no significant difference in dexmedetomidine therapy compared to control. Three trials, however, found a significant difference between the acetaminophen treatment and control groups. Conclusion: Acetaminophen was linked to a decreased risk of postoperative acute renal injury, while steroids had no benefit and aminophylline treatment could be justified.

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“…We have previously shown that high-dose methylprednisolone (MP) reduces activation of neutrophils, which are important first line actors in ischemia/reperfusion injury. 6 Furthermore, we have observed that MP conserves endothelial glycocalyx, a major determinant of capillary permeability and tissue edema. 7 The overall prognosis for congenital heart diseases has improved.…”

Section: Introductionmentioning

confidence: 90%

Reduction of Inflammation by High-Dose Methylprednisolone Does not Attenuate Oxidative Stress in Children Undergoing Bidirectional Glenn Procedure With or Without Aortic Arch or Pulmonary Arterial Repair

Keski‐Nisula

Arvola

Jahnukainen

et al. 2020

Journal of Cardiothoracic and Vascular Anesthesia

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The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase–Associated Lipocalin in Pediatric Heart Surgery*

Cited by 14 publications

References 23 publications

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

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

Cardiac surgery-associated acute kidney injury in newborns: A meta-analysis

Reduction of Inflammation by High-Dose Methylprednisolone Does not Attenuate Oxidative Stress in Children Undergoing Bidirectional Glenn Procedure With or Without Aortic Arch or Pulmonary Arterial Repair

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