Kidney Week

Abstract: SA-PO0141

Role of Nicotinamide Phophoribosyltransferase (NAMPT) in Regulating Nicotinamide Adenine Dinucleotide (NAD+) Metabolism and Tubular Injury Response During AKI

Session Information

• AKI: Mechanisms - 3
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Etzrodt, Valerie, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Valerie Etzrodt, MD

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

Binnu Gangadharan, PhD

• 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

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

Kyle Q. Vu

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

Yu Tao, MD, PhD

• Loyde, Erik Giovanny, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Erik Giovanny Loyde

• Suzuki, Takashi, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Takashi Suzuki, MS, PhD

• 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) is marked by a rapid decline in renal function and carries high mortality. A hallmark of AKI is a sharp decrease in kidney NAD+ levels, especially within proximal tubule cells—the primary targets of ischemic and toxic injury. Investigating the potential modulation of NAMPT, the rate limiting enzyme in the NAD+ Salvage pathway, we explored its role in AKI to better understand its contribution to NAD+ homeostasis and injury response.

Methods

A siRNA was used to lower NAMPT expression in human kidney cells (HK2). In vitro, acute injury was induced using TNFa, and various readouts such as RT-qPCR, Western Blot, NAD(H) levels were assessed. A proximal tubule specific murine model was utilized to deplete NAMPT expression (SLC24a1 CreERT2; Nampt (fl/fl)). Serum creatinine, total kidney cortex lysates were analyzed using various readouts such as RT-qPCR and immunohistochemistry. A murine model of systemic inflammation was used to induce acute kidney injury (LPS i.p. 17.5 mg/kg BW).

Results

Although NAMPT was upregulated in the serum of acutely injured mice, both in vitro and in vivo depletion of NAMPT in proximal tubule cells induced a clear injury phenotype. In HK-2 cells, NAMPT knockdown led to genotypic features of injury, including upregulation of markers such as LCN2, whereas overexpression of NAMPT had no detrimental effect. Notably, HK-2 cells downregulated NAMPT expression in response to inflammatory stimuli. As expected, pharmacological inhibition of NAMPT with FK866 resulted in intracellular NAD+ depletion and significantly increased the expression of kidney injury markers.

Conclusion

These findings indicate that NAMPT is essential for maintaining NAD+ homeostasis in proximal tubule cells, and its loss leads to increased susceptibility to injury. This underscores the critical role of NAD+ metabolism in protecting against acute kidney injury and highlights NAMPT as a potential therapeutic target.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ngns8th3