Kidney Week

Abstract: TH-PO077

Impaired De Novo NAD+ Biosynthesis Is a Feature of Pediatric AKI

Session Information

• AKI: Clinical, Outcomes, and Trials - Epidemiology and Pathophysiology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

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

Kyle Q. Vu

• 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

• Berg, Anders H., Cedars-Sinai Medical Center, Los Angeles, California, United States

Anders H. Berg, MD, PhD

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

Samir M. Parikh, MD, FASN

Background

Impaired cellular energy metabolism is a known feature of acute kidney injury (AKI). NAD+ is a critical cofactor required for ATP synthesis. Suppression of NAD+ biosynthesis, most notably the de novo pathway commencing from tryptophan, is a well-described feature of AKI and critical illness in animal models and humans. Reduction in flux through de novo NAD+ biosynthesis can be tracked non-invasively with urinary accumulation of the bottleneck metabolite quinolinate relative to tryptophan. Significantly, impaired NAD+ biosynthesis represents a therapeutic target in AKI as replacement of NAD+ via nutritional precursors of alternate NAD+ biosynthesis pathways can mitigate AKI severity in animals and early clinical trials in humans. To date, all studies evaluating de novo NAD+ biosynthesis impairment in clinical AKI have been performed in adult patients.

Methods

Discarded pediatric urine samples were collected from the laboratory of a tertiary care children’s hospital and sorted into groups: AKI, ICU, control (Con), based on patient status at the time of collection obtained from the medical record. Control urines were obtained from otherwise healthy children undergoing screening evaluations. NAD+ related metabolites were measured using liquid chromatography mass spectrometry.

Results

Urines from 26 children with AKI, 44 patients in the ICU, and 40 control patients were collected. Patients with AKI and/or critical illness exhibited accumulation of de novo NAD+ biosynthesis metabolites in the urine, including elevated quinolinate:tryptophan ratio (Con 0.971, AKI 15.1, ICU 5.69, p <0.001). In critically ill children, urine quinolinate:tryptophan ratio was elevated in patients with and without AKI (6.45 and 5.30 respectively, p <0.001 and 0.037 compared to Con).

Conclusion

To our knowledge, these data provide the first demonstration that impaired de novo NAD+ biosynthesis may be a feature of pediatric AKI and pediatric critical illness, as described in adults. Therefore, children may benefit from clinical trials targeting NAD+ replacement to mitigate AKI and severity of critical illness

Funding

• NIDDK Support