Abstract: FR-PO0924
Metabolic Profiling of Neonatal Kidneys and Response to AKI
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Hyatt, Dylan Michael, University of California San Diego Department of Pediatrics, La Jolla, California, United States
- Rodrigues Muller, Cynthia, University of California San Diego Division of Nephrology-Hypertension, La Jolla, California, United States
- Singh, Prabhleen (Sheena), University of California San Diego Division of Nephrology-Hypertension, La Jolla, California, United States
Background
Preterm infants in the neonatal ICU are at risk of nephrotoxic AKI, while undergoing nephrogenesis during a critical period of kidney development. During nephrogenesis, glycolytic metabolism has been shown to influence cell fate. Given the major role of cell metabolism in adult AKI, metabolic programming during this critical developmental period is likely to impact response and recovery in AKI but remains completely unexplored.
Methods
Neonatal mice undergo postnatal period of nephrogenesis from postnatal day 0 (P0) through P4 and thus serve as an apt model for ex-utero nephrogenesis. We used a nephrotoxic model of AKI in C57BL/6 mice pups with the administration of indomethacin (oral 5 mg/kg) from P1-P3 and gentamicin (intraperitoneal (IP), 80mg/kg) on P1 and P3, while control mice received placebo. Kidneys were harvested at P0 and P5 to study mRNA and protein expression of glycolytic enzymes at baseline and in response to nephrotoxins using digital droplet PCR and western blot with B-actin as an endogenous control.
Results
There was a significant increase in the mRNA expression of phosphofructokinase liver type (PKF-L) and protein expression of lactate dehydrogenase A (LDHA) in P5 vs. P0 (p < 0.005), and a trend for increase in hexokinase (HK1) and lactate dehydrogenase B (LDHB). In response to nephrotoxic AKI, there was a trend for increased protein expression of PFK L and HK1 (p=0.05). Expression of other metabolic enzymes at baseline and in response to AKI are undergoing.
Conclusion
Our results show an upregulation in glycolytic enzymes during postnatal nephrogenesis, likely to support cell proliferation in the developing kidney via glycolysis. There appears to be a further increase in glycolytic enzymes in response to AKI. We aim to understand the mechanistic underpinnings of metabolic response to AKI in the developing kidney and its impact on long-term kidney function.
Funding
- NIDDK Support