Kidney Week

Abstract: FR-PO0344

Loss of NAD+ Salvage Biosynthesis Modulates Tubular Injury in AKI

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Gangadharan, Binnu, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Binnu Gangadharan, PhD

• Etzrodt, Valerie, Yale New Haven Health, New Haven, Connecticut, United States

Valerie Etzrodt, MD

• Chen, Liping, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Liping Chen, MS

• Clark, Amanda J., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Amanda J. Clark, MD

• Saade, Marie Christelle, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Marie Christelle Saade, MD

• Tao, Yu, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Yu Tao, MD, PhD

• Vu, Kyle Q., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Kyle Q. Vu

• Alhumaidi, Rahil, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Rahil Alhumaidi, MA

• Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Samir M. Parikh, MD, FASN

Background

Acute kidney injury (AKI) involves rapid tubular epithelial damage and metabolic stress. Maintenance of nicotinamide adenine dinucleotide (NAD+) is critical for cellular energy balance and stress adaptation. In most cells, NAD+ is primarily generated through the salvage pathway, which recycles nicotinamide via the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT). Impaired NAD+ salvage is associated with reduced cellular resilience and increased susceptibility to injury; however, its role in regulating tubular injury responses during AKI remains poorly defined. As the rate-limiting enzyme in NAD+ salvage, NAMPT was investigated for its role in tubular injury responses during AKI.

Methods

In murine models, NAMPT was deleted in proximal tubular epithelial cells using an inducible CreERT2 system with tamoxifen administration. Acute kidney injury was induced by LPS. Kidneys from control and NAMPT-deficient mice were analyzed for injury marker expression by qPCR and Western blot. Renal function was assessed by BUN, serum creatinine, urinary protein and glucose levels. Histology and immunofluorescence were performed to evaluate tubular injury. In vitro, HK-2 cells with NAMPT knockdown were treated with TNF-α to induce injury and tubular injury markers were assessed.

Results

In murine models, proximal tubular NAMPT deletion was confirmed by qPCR, Western blot, and immunostaining. NAMPT-deficient mice exhibited increased expression of tubular injury markers, including KIM-1 and NGAL, along with elevated serum creatinine and BUN levels compared to controls. Urinary protein and glucose levels were also increased, consistent with worsened tubular injury and dysfunction. HK-2 cells with NAMPT knockdown or pharmacological inhibtion (with FK866) exhibited increased tubular injury marker expression and depletion of intracellular NAD+, consistent with the in vivo findings.

Conclusion

These findings suggest that NAMPT is important for sustaining NAD+ balance in proximal tubular epithelial cells, and its deficiency heightens sensitivity to injury and metabolic stress. Thus, NAMPT may represent a potential therapeutic target in acute kidney injury (AKI) by preserving tubular metabolic resilience and limiting injury progression.

Acknowledgment

NIDDK Support

Funding

• NIDDK Support