(17) Kynurenic acid levels in preterm neonates with and without acute kidney injury

Background: Acute kidney injury (AKI) is common in preterm neonates and is associated with increased morbidity and mortality. In animal and human adult studies, decreases in nicotinamide adenine dinucleotide (NAD) have been associated with AKI. The synthesis of NAD occurs through the tryptophan pathway and a major branch point in this pathway, kynurenine metabolism, can result in kynurenic acid (KYNA) or alternatively continue metabolism into NAD. We have recently identified KYNA as a metabolite present in the urine of preterm neonates.

Objectives: To compare levels of KYNA in preterm neonates with and without AKI.

Design/Methods: A prospective observational study of preterm neonates born < 32 weeks gestational age was completed in 2021-2023. AKI was diagnosed using the neonatal modified KDIGO definition using both increases in serum creatinine and decreases in urine output. Urine collection was performed with cotton in participants’ diapers and samples were collected every 6 hours and frozen at -80 degrees Celsius. KYNA levels were quantified using mass spectrometry. For infants who developed AKI, only KYNA levels observed before AKI diagnosis were included. A Mann-Whitney test was used to evaluate the significance of KYNA levels in AKI and non-AKI groups. A receiver operator characteristics (ROC) analysis was performed to calculate area under the curve (AUC).

Results: 32 participants with a median birth weight of 1130 grams (IQR 1010-1368) and gestational age of 29 weeks (IQR 27-29.75) were included. Five participants developed AKI, four with stage 1 injury and one with stage 2 injury. Urine collection began at a mean 3.7 days of age and until a mean 13.3 days of age. KYNA levels decrease with increasing gestational age (Spearman’s correlation = -0.36, p < 0.05) and increasing birth weight (Spearman’s correlation = -0.56, p < 0.01) (Figure 1). Participants with AKI had significantly higher KYNA levels compared to those without AKI (p < 0. 01) (Figure 2). Figure 3 shows the KYNA levels of AKI patients with their time of AKI diagnosis. The AUC to diagnose AKI with KYNA is 0.849 (p < 0.01) (Figure 4).

Conclusion: Preterm neonates with AKI have significantly higher levels of KYNA than those without AKI. Future preterm neonatal AKI studies should consider including urine collection to evaluate KYNA levels.