Abstract: TH-PO289

Antioxidant-Mediated Improvement of Kidney Function in the Adult LBW Neonate

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Abdulmahdi, Wasan, New York Medical College, Valhalla, New York, United States
  • Jules, Edson, New York Medical College, Valhalla, New York, United States
  • Marji, Noor, New York Medical College, Valhalla, New York, United States
  • Nesi, Lauren M., NYMC, Scarsdale, New York, United States
  • Rabadi, May M., Columbia University Medical Center, New York, New York, United States
  • Abdelrahman, Magdi, New York Medical College, Valhalla, New York, United States
  • Ratliff, Brian B., New York Medical College, Valhalla, New York, United States
Background

Low birth weight (LBW), as defined by the World Health Organization, is a birth weight of less than 5.5 pounds. Maternal malnourishment during pregnancy impairs nephrogenesis in the developing embryo and is a major cause of LBW. As a result, the LBW neonate has a decreased nephron compliment and is susceptible to kidney disease and hypertension. However, investigation is still required to fully understand disease progression in LBW neonates and the underlying causes. Hence, we established a pregnant mouse malnourishment model to further investigate the causes that promote kidney disease in LBW neonates and to examine potential therapeutic treatments.

Methods

Pregnant CD-1 mice were started on a food restricted diet on day 9 of gestation and were maintained on the diet throughout the rest of gestation. The malnourished diet consisted of a 50% daily caloric reduction combined with administration of a low protein chow (6%, vs control chow composed of 26% protein). We measured body weight, blood pressure, renal blood perfusion, glomerular filtration rate (GFR) and blood glucose levels in LBW mice 1, 3 and 6 months postpartum. We also included a direct analysis of gender differences in the aforementioned parameters. Since preliminary experiments indicated a dramatic increase of reactive oxygen specious (ROS) in the circulation of adult LBW neonates, we examined the therapeutic efficacy of tempol, a ROS quencher, which was administrated (via drinking water) to these animals.

Results

Our results showed that female and male LBW mice at 1, 3 and 6 months have higher blood pressure and blood glucose levels, while body weight, GFR and renal blood perfusion are reduced, as compared to controls. Conversely, tempol treatment improved GFR and renal blood flow, while it decreased blood glucose levels and blood pressure. Body weight was unaffected by tempol treatment. We did not observe any gender based differences in LBW mice.

Conclusion

In conclusion, our results confirmed the validity of our mouse model and indicated our model develops pathologies within 6 months postpartum that closely resemble pathologies observed in human LBW neonates. The potential efficacy of antioxidant based therapies was also highlighted when tempol treated mice showed improved kidney function, decreased blood pressure and blood glucose levels.