Abstract: SA-PO0706
Comprehensive Analysis of Metabolic Alterations Resulting from Renal Insufficiency During Pubertal Growth in Male and Female Rats
Session Information
- Pediatric Nephrology: Transplantation, Hypertension, AKI, Genetics, and Developmental Diseases
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Kriegel, Alison J., Augusta University, Augusta, Georgia, United States
- Patil, Chetan N., Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Reho, John J, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Grobe, Justin L, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Background
Pediatric patients with advanced CKD experience somatic growth and development with impaired kidney function. Clinical studies report an accelerated worsening of renal function around the time of puberty and overall impact to growth. The goal of this study was to determine the impact of renal insufficiency on pubertal growth and metabolism in male and female rats.
Methods
Male and female Sprague Dawley rats (4-5 weeks of age; food and water ad libitum) underwent nuclear magnetic resonance imaging (NMR) to assess body composition followed by randomization to naïve (N; n=6M/4F), sham surgery (S; n=9M/4F) or 5/6 nephrectomy (5/6Nx; n=11M/8F) groups. Two weeks later rats underwent a second NMR followed by 4 days of housing in a Promethion System. Generalized linear model (GLM) to model the relationship between energy expenditure, food intake, fat mass and/or fat mass. Terminal serum samples were analyzed by biochemical panel and metabolic hormone discovery assay.
Results
No differences between N and S control rats were detected. Body weight and calculated surface area were lower in 5/6Nx than control groups. Total fat and lean mass were lower in 5/6Nx rats. When compared to N or S groups, 5/6Nx animals had higher water consumption and lower food intake, energy production and activity during their active phase. Energy expenditure tended to be lower in 5/6Nx rats when corrected for FFM and/or food intake; however, food intake corrected for FFM was lower only in males. Differences in food intake between 5/6Nx and control groups were lost when corrected for fat mass or FFM + fat mass. The 5/6Nx rats of both sexes have increased serum gastric inhibitory peptide (GIP) and peptide YY (PYY) levels and reduced serum leptin and glucose levels.
Conclusion
Renal insufficiency during pubertal growth impaired overall growth, changed body composition, and altered metabolism, activity and drinking behavior. Though the food intake was reduced in 5/6Nx rats during the active phase, correction for body composition eliminated that difference. While increased PYY levels may contribute to reduced food intake, these data suggest that reduced food intake alone is not driving the growth impairment and body composition changes. Further, renal insufficiency resulted in similar changes in males and females in most, but not all, phenotypes.
Funding
- Private Foundation Support