Urinary Metabolomics Predict Acute Kidney Injury in Very-Low-Birth-Weight Infants with Patent Ductus Arteriosus

Very preterm infants with immature kidneys exhibit high vulnerability to acute kidney injury (AKI). While AKI is associated with adverse outcomes, serum-creatinine-based diagnostics prove unreliable in early risk assessment of kidney damage. This pilot study investigated ¹H-NMR spectroscopy-based metabolomics for the identification of very-low-birth-weight (VLBW < 1500 g) infants at risk of AKI before and during indomethacin treatment for patent ductus arteriosus (PDA). Longitudinal urine samples (0 h, 12 h, 36 h, 84 h, 120 h, 14 d, 28 d) from 12 VLBW infants receiving indomethacin for hemodynamically significant PDA were analyzed by ¹H-NMR spectroscopy. In total, 150 urinary metabolites were annotated and single-metabolite and multivariate analyses were performed. At 36 h after treatment initiation, three patients (25%) developed AKI (KDIGO criteria). Principal component analysis (PCA) revealed significant differences in urinary metabolic profiles between the AKI and non-AKI groups 12 h after indomethacin initiation. Before treatment, five metabolites were significantly lower in the AKI group: adenine, creatine, dimethylglycine, 1-methylnicotinamide, and methylmalonic acid. Urinary creatine/creatinine (AUC 0.97) and 1-methylnicotinamide/creatinine (AUC 0.93) exhibited promising prognostic accuracy for the prediction of AKI. 1-methylnicotinamide/creatinine concentrations remained persistently reduced during the study. In conclusion, urinary metabolomics, particularly creatine and 1-methylnicotinamide levels, may serve as valuable non-invasive biomarkers for identifying VLBW infants at risk of AKI.