Early septic insult in neonatal pigs increases serum and urinary soluble fas ligand and decreases kidney function without inducing significant renal apoptosis

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Abstract

Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs. Serum creatinine and urea nitrogen concentrations were increased by ∼39% and 46%, respectively, following 6h of CLP in the pigs. The urinary level of NGAL, an early marker of AKI was also elevated by ∼71% in the septic pigs. The basal concentration of sFasL in the serum and urine of neonatal pigs was similar. Six hours of CLP significantly increased serum and urine sFasL levels in the pigs by ∼24% and 68%, respectively. However, there was no evidence of caspase activation to suggest an induction of cellular apoptotic process in the kidneys of the septic pigs. These findings suggest that an increase in circulating and urinary sFasL during early septic AKI in neonatal pigs is not associated with renal apoptosis.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalRenal Failure
Volume39
Issue number1
DOIs
StatePublished - Oct 20 2017

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Fas Ligand Protein
Swine
Apoptosis
Kidney
Serum
Acute Kidney Injury
Punctures
Ligation
Sepsis
Urine
Kidney Diseases
Caspases
Bacteremia
C-Reactive Protein
Urea
Blood Proteins
Creatinine
Nitrogen

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Nephrology

Cite this

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title = "Early septic insult in neonatal pigs increases serum and urinary soluble fas ligand and decreases kidney function without inducing significant renal apoptosis",
abstract = "Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs. Serum creatinine and urea nitrogen concentrations were increased by ∼39{\%} and 46{\%}, respectively, following 6h of CLP in the pigs. The urinary level of NGAL, an early marker of AKI was also elevated by ∼71{\%} in the septic pigs. The basal concentration of sFasL in the serum and urine of neonatal pigs was similar. Six hours of CLP significantly increased serum and urine sFasL levels in the pigs by ∼24{\%} and 68{\%}, respectively. However, there was no evidence of caspase activation to suggest an induction of cellular apoptotic process in the kidneys of the septic pigs. These findings suggest that an increase in circulating and urinary sFasL during early septic AKI in neonatal pigs is not associated with renal apoptosis.",
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N2 - Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs. Serum creatinine and urea nitrogen concentrations were increased by ∼39% and 46%, respectively, following 6h of CLP in the pigs. The urinary level of NGAL, an early marker of AKI was also elevated by ∼71% in the septic pigs. The basal concentration of sFasL in the serum and urine of neonatal pigs was similar. Six hours of CLP significantly increased serum and urine sFasL levels in the pigs by ∼24% and 68%, respectively. However, there was no evidence of caspase activation to suggest an induction of cellular apoptotic process in the kidneys of the septic pigs. These findings suggest that an increase in circulating and urinary sFasL during early septic AKI in neonatal pigs is not associated with renal apoptosis.

AB - Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs. Serum creatinine and urea nitrogen concentrations were increased by ∼39% and 46%, respectively, following 6h of CLP in the pigs. The urinary level of NGAL, an early marker of AKI was also elevated by ∼71% in the septic pigs. The basal concentration of sFasL in the serum and urine of neonatal pigs was similar. Six hours of CLP significantly increased serum and urine sFasL levels in the pigs by ∼24% and 68%, respectively. However, there was no evidence of caspase activation to suggest an induction of cellular apoptotic process in the kidneys of the septic pigs. These findings suggest that an increase in circulating and urinary sFasL during early septic AKI in neonatal pigs is not associated with renal apoptosis.

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