Abstract: FR-PO424
Metabolic Changes and Growth Impairment in a Rat Model of Juvenile CKD
Session Information
- Pediatric Nephrology - I
November 04, 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
- Kriegel, Alison J., Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Patil, Chetan N., Medical College of Wisconsin, Milwaukee, Wisconsin, United States
- Schwasinger, Emma T., Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Background
Many pediatric patients living with chronic kidney disease (CKD) experience growth impairment. Metabolic changes accompanying this are incompletely understood. Our laboratory has applied the surgical 5/6 nephrectomy (5/6Nx) model to study CKD in adult rats. The goal of this study was to determine if application of 5/6Nx in juvenile rats could be used to study CKD-related growth impairment. We hypothesized that 5/6Nx surgery in juvenile rats would lead to impaired somatic growth and metabolic dysregulation.
Methods
Young male Sprague Dawley rats (4-5 weeks of age; food and water ad libitum) underwent nuclear magnetic resonance imaging (NMR) in the to assess body composition and were randomized to naïve (N; n=6), Sham (S; n=9) or 5/6 nephrectomy (5/6Nx; n=11) groups. Two weeks later rats underwent a second NMR followed by 4 days of housing in a Promethion (Sable Systems International), a non-invasive metabolic phenotyping system.
Results
Rats from N and S groups more than doubled their body mass the initial two weeks of the study (2.27±0.22 and 2.43±0.19-fold, respectively), while 5/6Nx rats gained less mass (1.47±0.19-fold, p<0.05). NMR analysis revealed that the mean % fat mass at baseline averaged 4 to 4.5%. The % fat mass tend to increase in N and S rats (5.65±0.20% and 6.07±0.20 %, respectively) while dropping precipitously in 5/6Nx rats (2.08±0.52%; p <0.05 vs. control groups). The % lean mass showed an inverse relationship to that of % fat mass. Hydration (body water as % of body weight) increased in 5/6Nx rats (71.68±0.38%) when compared to N or S groups (69.06±0.15% and 68.75±0.30%, respectively). Promethion system data revealed that, when compared to N or S groups, 5/6Nx animals had significantly lower daily food intake and energy expenditure and were less active during their active phase. The respiratory exchange ratio was higher in 5/6Nx rats suggesting increased carbohydrate metabolism. The 5/6Nx animals exhibited greater water consumption during their inactive period than control groups.
Conclusion
Application of the 5/6Nx surgical model of CKD to juvenile rats impaired somatic growth, changed body composition, and altered metabolism, activity and drinking behavior. This indicates that this model recapitulates characteristics of CKD-related growth impairment in pediatric patients and may be a useful tool for developing new therapies to counteract these changes.
Funding
- Private Foundation Support