Abstract: FR-PO0197
Plasma Metabolomic Changes Associated with Mortality and AKI in a Polytrauma Pig Model
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Ragi, Nagarjunachary, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Debnath, Subrata, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Feng, Tianqing, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Trevino, Esmeralda, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Castaneda, Maria G, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Mireles, Allyson A, 59th Medical Wing, Lackland AFB, Texas, United States
- Ng, Patrick C, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Background
Acute kidney injury (AKI) is a common complication following polytrauma, driven by hemorrhagic shock, hypoperfusion, and inflammation. Porcine models closely mimic human physiology and enable controlled investigation of trauma-induced organ dysfunction. In this study, we employed a swine polytrauma model (Sus scrofa, 45–65 kg) to evaluate kidney injury over time using metabolomics approach. Our objective was to identify early metabolic changes that reflect evolving renal dysfunction and assess their potential as biomarkers of AKI and mortality.
Methods
Plasma samples were collected at baseline (T1), post-polytrauma-induced hemorrhagic shock (T2), after 60 minutes of resuscitative endovascular balloon occlusion of the aorta (REBOA, T3), and at multiple time points up to the end of study (T9) during a 120-minute post-REBOA observation period. LC-MS/MS-based metabolomics was used to quantify key metabolites, and correlation analyses were performed to assess associations with creatinine.
Results
Adenine levels were increased significantly at T2 and T3, with early elevation associated with increased mortality risk (p < 0.05). Creatinine increased 2–3 fold at T9, suggesting reduced glomerular filtration. Adenine and quinolinic acid increased 3.8-fold and 1.4-fold, respectively. TMAP, a novel marker of kidney function, increased 2.17-fold from T1 to T9, with a progressive increase throughout the study. ADMA and SDMA, uremic toxins linked to endothelial dysfunction, both increased ~2-fold at T9 compared to T1. Correlation analyses revealed significant associations between creatinine and TMAP (r = 0.6494, p = 0.05), ADMA and SDMA (r = 0.9783, p < 0.01), and quinolinic acid (r = 0.6681, p = 0.04), supporting the roles of these metabolites in the pathophysiological progression of trauma-induced AKI.
Conclusion
This study identified that an increase in plasma adenine within minutes of polytrauma was associated with early mortality, while TMAP, ADMA, SDMA, and quinolinic acid are associated with evolving AKI. These biomarkers may help identify various therapeutic targets to mitigate against or prevent multi-organ injury related to trauma. It is important to note that elevated creatinine levels in this context may also result from muscle injury rather than reduced GFR alone.