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Kidney Week

Abstract: TH-OR041

Effects of Hyperoxia with and without Klotho Supplementation in a Murine Model of Post-Natal Nephrogenesis

Session Information

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Ali, Mohammed Farhan, University of Miami, Miami, Florida, United States
  • Batlahally venkatarayappa, Sunil kumar, University of Miami, Miami, Florida, United States
  • Benny, Merline, University of Miami, Miami, Florida, United States
  • Rojas, Claudia P., University of Miami, Miami, Florida, United States
  • Da Silva, Naimeh, University of Miami, Miami, Florida, United States
  • Freundlich, Michael, University of Miami, Miami, Florida, United States
  • Abitbol, Carolyn L., University of Miami, Miami, Florida, United States
  • Defreitas, Marissa J., University of Miami, Miami, Florida, United States
  • Young, Karen C., University of Miami, Miami, Florida, United States
Background

Preterm infants are born during active nephrogenesis and exposure to high oxygen levels has been proposed to cause kidney related injury due to oxidative stress. Studies investigating the effects of hyperoxia on nephrogenesis are limited and have not evaluated whether these effects are reversible by administration of an agent with antioxidant properties. The aim of our study was to determine whether the administration of exogenous Klotho, a multi-functional protein that is known to diminish oxidative stress and apoptosis, attenuates hyperoxia induced glomerular and tubular injury in rats during nephrogenesis.

Methods

Newborn rat pups were raised in hyperoxia (85% oxygen for 3 weeks and then recovered in room air for 3 weeks) or room air (21% oxygen for 6 weeks). Klotho was administered intraperitoneally to half of the pups in both groups every other day for the first 3 weeks. All pups were sacrificed at the end of 6 weeks and the kidneys were assessed for glomerular diameter and area using Image J software, and tubular injury using a tubular injury scoring system (0- no injury, 5- >75% of tubules injured).

Results

Hyperoxia exposed rats had greater glomerular diameter, area and tubular injury scores. The administration of Klotho attenuated tubular injury (Figure A) and prevented glomerulomegaly (Figure B).

Conclusion

The findings of this study demonstrate that hyperoxia exposure during active nephrogenesis in the neonatal rat pups results in increased glomerular size and tubular injury and that the exogenous administration of Klotho in these pups attenuates hyperoxia induced tubular injury and prevents glomerulomegaly at 6 weeks. Future studies aimed at exploring the therapeutic potential of Klotho in neonatal models of kidney injury are needed.

Funding

  • Private Foundation Support