Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

Abstract

Introduction AKI staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI associated renal function in preterm infants. The study was comprised of 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis. Methods Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad spectrum NMR-metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI. Results There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI and no-AKI. Pathway analysis revealed similarities to cholingeric neurons, prenatal nicotine exposure on pancreatic β cells, and Amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated of AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that were uniquely correlated to gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism. Conclusions Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles were correlated with gestational age. Further studies in larger cohorts are needed to validate these results.

Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study

“…For example, Beger et al identified homovanillinic acid sulfate, a dopamine metabolite as the most important marker in the urine of children who developed AKI after cardiac surgery [21]. This finding was confirmed by Mercier et al investigating the urine of neonates with AKI [29]. By contrast, aromatic compounds other than 3-indoxylsulfate and hippurate are not among the important metabolites in our study.…”

“…Previous human AKI studies resulted in the identification of a variety of potential metabolite biomarkers [14,24]. Interestingly, almost no overlap exists between the respective metabolites [28][29][30][31][32][33][34] and the metabolites identified in our study. For example, Beger et al identified homovanillinic acid sulfate, a dopamine metabolite as the most important marker in the urine of children who developed AKI after cardiac surgery [21].…”

Renal Function Profiles in Preterm Neonates With Birth Asphyxia Within the First 24 H of Life

“…BA has been often reported as one of the most common early and late causes of renal function decline in neonates (30). In this study, we also found that asphyxia was significantly associated with an increased risk of impaired renal function in preterm neonates within the first day after birth.…”

A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol

“…Interindividual differences in levels of metabolites that are substrates for cisplatin transporters may help identify individualized risk of cisplatin AKI. [46][47][48][49][50] Proximal tubule mitochondria are a primary target of cisplatin nephrotoxicity and cisplatin has been shown to alter metabolites associated with oxidant stress (eg, glutathione) and mitochondrial dysfunction (eg, fatty acids) in response to injury. 51,52 Metabolites associated with oxidant stress or mitochondrial dysfunction may be metabolic markers of early nephrotoxicity.…”