Kidney Week

Abstract: SA-PO599

Neonatal Hyperoxia Contributes to Kidney Injury and Differential Kidney Gene Expression in Adult Rats

Session Information

• Pediatric Nephrology - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Defreitas, Marissa J., University of Miami School of Medicine, Miami, Florida, United States

Marissa J. Defreitas,

• Schmidt, Augusto F., University of Miami School of Medicine, Miami, Florida, United States

Augusto F. Schmidt,

• Levine, Amanda, University of Miami School of Medicine, Miami, Florida, United States

Amanda Levine,

• Kulandavelu, Shathiyah, University of Miami School of Medicine, Miami, Florida, United States

Shathiyah Kulandavelu,

• Chen, Pingping, University of Miami School of Medicine, Miami, Florida, United States

Pingping Chen,

• Tian, Runxia, University of Miami School of Medicine, Miami, Florida, United States

Runxia Tian,

• Rojas, Claudia Patricia, Memorial Healthcare System, Hollywood, Florida, United States

Claudia Patricia Rojas,

• Abitbol, Carolyn L., University of Miami School of Medicine, Miami, Florida, United States

Carolyn L. Abitbol,

• Wu, Shu, University of Miami School of Medicine, Miami, Florida, United States

Shu Wu,

• Young, Karen, University of Miami School of Medicine, Miami, Florida, United States

Karen Young,

• Benny, Merline, University of Miami School of Medicine, Miami, Florida, United States

Merline Benny,

Background

Neonatal hyperoxia exposure causes short- and long-term kidney injury and impaired kidney development. However, the mechanisms underlying this programming are largely unknown. Here, we test the hypothesis that neonatal hyperoxia induces renal histomorphometry changes and altered kidney gene expression in adult rats.

Methods

Newborn rats (N=14) randomly assigned to normoxia (RA; n=8) or hyperoxia (HO; n=6) (85% O₂) from postnatal day 1 to 14, were recovered in normoxic conditions until 1 year of life. At 1 year of life, kidney and body weight were measured. Renal histomorphometry was assessed for glomerular size (diameter and area) and tubular injury score. RNA-seq of the whole kidney was done (n=4/group) to assess the transcriptional effects of neonatal hyperoxia at 1 year. Data are expressed as mean ± SD and analyzed by Student’s T test.

Results

At 1 year, kidney weight/body weight was significantly lower in the HO compared to the RA group (1.98 ± 0.57 mg/gm vs 3.99 ± 2.05 mg/gm, respectively, p=0.03). There was significant glomerulomegaly (Figure 1A) and a trend towards increased tubular injury score (Figure 1B) in the HO compared to RA group. Neonatal hyperoxia exposure differentially regulated genes in 1 year old kidneys. Gene set enrichment analysis showed that the most downregulated genes were related to “kidney development” (Figure 1C) while the most upregulated included genes involved in “brush border”, “extracellular matrix binding”, and “glutathione peroxidase and transferase activity” (Figure 1D).

Conclusion

Neonatal HO exposure was associated with sustained glomerular and tubular injury and decreased nephron mass in adult rats. This was accompanied by a downregulation of kidney developmental gene expression and an upregulation of antioxidant and tissue repair gene expression. Further studies to determine how antioxidant therapies could alter the programming of kidney injury after neonatal HO exposure are important.

Funding

• Other NIH Support