Pediatric acute kidney injury is associated with impairment in nicotinamide adenine dinucleotide (NAD+) metabolism.

Marie Christelle Saade, Amanda J Clark, Samir M Parikh, Brenda Mendoza Flores, Kyle Q Vu, Isaac J Pence, Anders Berg

Journal: Pediatric nephrology (Berlin, Germany) 2025;40(9):2967-2972

PMID: 40353859

Abstract

BACKGROUND

Acute kidney injury (AKI) is highly prevalent among hospitalized children, but there is no treatment. Impaired de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis measured via elevation of the urine quinolinic acid-to-tryptophan ratio (uQ:T) is a feature of AKI that has been described in preclinical models and humans with AKI. Small prospective trials to restore NAD+ abundance with NAD+ precursor supplementation have shown promise in the prevention and treatment of AKI. It is not known whether pediatric patients also develop suppression of NAD+ biosynthesis during AKI, but such information will be critical before children can be included in NAD+ -based clinical trials to treat or prevent AKI.

METHODS

An observational cross-sectional study was performed on convenience urine samples from children hospitalized in a tertiary care children's hospital. Samples were split into five groups: outpatient controls, floor controls, ICU controls, floor AKI, and ICU AKI. Clinical data were collected from the medical record, and metabolites were measured using targeted mass spectrometry. Patients with AKI were compared to their respective controls. A multivariate linear regression was used to assess whether demographic variables were independently associated with uQ:T, and odds of AKI were assessed in serial uQ:T tertiles using multivariate logistic regression models that adjusted for patient variables.

RESULTS

Sixty-nine control patients (39 outpatient, 10 floor, and 20 ICU controls) and 22 AKI patients (12 floor and 10 ICU) were enrolled. uQ:T was elevated in patients with AKI compared to their respective controls. No demographic variables were independently associated with uQ:T, and when adjusting for patient demographic and clinical variables, the odds of AKI increased serially with uQ:T tertile.

CONCLUSIONS

Elevated uQ:T is a feature of pediatric AKI. The present results warrant further exploration in observational and potentially interventional studies with NAD+ precursor therapies.

Address: Pediatrics, Pediatric Nephrology and Children's Medical Center Dallas, University of Texas Southwestern, Dallas, USA. [email protected].; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, USA.; Internal Medicine, Nephrology, University of Texas Southwestern, Dallas, USA.; Internal Medicine, Nephrology, University of Texas Southwestern, Dallas, USA.; Pediatrics, Pediatric Nephrology and Children's Medical Center Dallas, University of Texas Southwestern, Dallas, USA.; Internal Medicine, Nephrology, University of Texas Southwestern, Dallas, USA.; Biomedical Engineering, University of Texas Southwestern, Dallas, USA.; Pathology, Cedars-Sinai Medical Center, Los Angeles, USA.; Internal Medicine, Nephrology, University of Texas Southwestern, Dallas, USA.; Pharmacology, University of Texas Southwestern, Dallas, USA.

DOI: 10.1007/s00467-025-06791-5

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https://dx.doi.org/10.1007/s00467-025-06791-5

MeSH Terms: Humans, Male, Acute Kidney Injury, Female, Cross-Sectional Studies, Child, Child, Preschool, NAD, Infant, Quinolinic Acid, Tryptophan, Adolescent, Biomarkers