The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase-Associated Lipocalin in Pediatric Heart Surgery.
OBJECTIVE
Plasma neutrophil gelatinase-associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase-associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase-associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase-associated lipocalin concentrations in pediatric heart surgery.


METHODS
Two separate double-blinded randomized trials.


METHODS
PICU at a university-affiliated hospital.


METHODS
Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction.


METHODS
First trial (neonate trial), 40 neonates undergoing open-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15).


RESULTS
Plasma neutrophil gelatinase-associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase-associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase-associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase-associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase-associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001).


CONCLUSIONS
Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase-associated lipocalin levels. Neutrophil gelatinase-associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase-associated lipocalin levels as a kidney injury marker in pediatric heart surgery.
1Department of Anesthesiology and Intensive Care Medicine, Peijas Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 2Department of Anesthesiology and Intensive Care Medicine, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3Department onf Pediatric Cardiac and Transplantation Surgery, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 4Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Eero J
EJ
Pesonen
Pertti K
PK
Suominen
Juho
J
Keski-Nisula
Ilkka P
IP
Mattila
Paula
P
Rautiainen
Timo
T
Jahnukainen
D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology; D000209:Acute-Phase Proteins / Q000187:drug effects; D015415:Biomarkers / Q000097:blood*; D006348:Cardiac Surgical Procedures; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006785:Hospitals, University; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000187:drug effects
D000209:Acute-Phase Proteins; D015415:Biomarkers; D005938:Glucocorticoids; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D008775:Methylprednisolone