Examining NAD+ Production and Consumption Imbalances and the Potential Protective Roles of NAD+ Supplements in Acute Kidney Injury
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Praveena Prasad
Exhibition Number 202
Abstract
Nicotinamide Adenine Dinucleotide (NAD+) is a central molecule which functions as a redox cofactor for several fundamental biochemical processes involved in metabolism and as a co-substrate for signaling enzymes. Acute Kidney Injury (AKI) is a rapidly growing global health crisis, affecting over 850 million people worldwide. Notably, AKI is one of the few diseases in humans directly correlated with disrupted NAD+ homeostasis. However, what remains unknown is whether NAD+ depletion in AKI is driven by impaired production or excessive consumption, leading to imbalances in flux and homeostasis. To answer this, we use a cisplatin-induced AKI mouse model and stable isotope tracing with [2,4,5,6-²H] nicotinamide (NAM) and [U-¹³C] tryptophan (Trp), coupled with liquid chromatography-mass spectrometry (LC-MS) and a multi-omics approach. Using this method, we measure both steady-state metabolite levels and whole-body NAD+ metabolic turnover and flux. Our data reveal that AKI disrupts NAD+ metabolism and NAM homeostasis across multiple tissues, creating metabolic bottlenecks resulting in impaired NAD+ synthesis under AKI conditions. Isotope tracing data with ²H indicates that NAD+ production via the salvage pathway is dysregulated, particularly in the spleen and duodenum. However, preliminary data from [U-¹³C] tryptophan tracing demonstrates increased NAD+ synthesis and release of NAM into the circulation which could be compensatory for disrupted Salvage synthesis across tissues. Collectively, our findings significantly advance our understanding of metabolic shifts in AKI and pave the way for translational efforts to evaluate the protective potential of NAD+ precursor supplementation as a therapeutic strategy.
Importance
This study would shed light on how acute conditions of stress like Acute Kidney Injury could impact the fundamental biochemical reactions of NAD+ metabolism thereby disrupting several crucial cellular processes leading to accelerated ageing. These results would have a direct translational effect by helping to identify novel targets and biomarkers which could contribute to developing enhanced therapeutic interventions and push efforts towards modulating metabolism to reduce cellular stress and thereby ameliorate kidney injury and disease.