Postdoctoral Fellow Indiana University Indianapolis, Indiana, United States
Background: Polyamines (putrescine, spermidine, and spermine) are critical molecules in living cells, playing key roles in processes such as cell proliferation, transcription, and translation. Their significance in kidney biology is particularly notable, as studies have shown that alterations in polyamine metabolism are a common feature across various murine models of kidney injury. However, the modulation of the polyamine pathway has yielded mixed outcomes, ranging from protective phenotype to tissue exacerbation depending on the kidney injury model. Methods: These conflicting findings prompted us to model kidney polyamine dynamics over specific disease timelines, which could help us better understand their kinetics over the course of injury to recovery. Here we propose a mathematical model of kidney polyamine kinetics based on ordinary differential equations from compartmentalization of each polyamine, rate constants derived from literature, RNA expression data, and observed quantitation of kidney metabolites following an endotoxin challenge. Results: The model captures the polyamine dynamics observed in a murine endotoxemia model and demonstrates relevant changes in kidney polyamine kinetics with a mean fold error of 2.0, 1.1, and 1.11 for putrescine, spermidine, and spermine respectively. This is the first mathematical model and simulation to predict polyamine kinetics in a model of acute kidney injury. Conclusion: This kidney polyamine kinetics model is flexible, allowing for the integration of experimental data from other acute kidney injury models, which could be used to test additional hypotheses and refine our understanding of polyamine behavior in kidney injury and recovery.
