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

Abstract

Acute kidney injury (AKI) in critically ill children and adults is associated with significant short- and long-term morbidity and mortality. As serum creatinine- and urine output-based definitions of AKI have relevant limitations, there is a persistent need for better diagnostics of AKI. Nuclear magnetic resonance (NMR) spectroscopy allows for analysis of metabolic profiles without extensive sample manipulations. In the study reported here, we examined the diagnostic accuracy of NMR urine metabolite patterns for the diagnosis of neonatal and pediatric AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. A cohort of 65 neonatal and pediatric patients (0–18 years) with established AKI of heterogeneous etiology was compared to both a group of apparently healthy children (n = 53) and a group of critically ill children without AKI (n = 31). Multivariate analysis identified a panel of four metabolites that allowed diagnosis of AKI with an area under the receiver operating characteristics curve (AUC-ROC) of 0.95 (95% confidence interval 0.86–1.00). Especially urinary citrate levels were significantly reduced whereas leucine and valine levels were elevated. Metabolomic differentiation of AKI causes appeared promising but these results need to be validated in larger studies. In conclusion, this study shows that NMR spectroscopy yields high diagnostic accuracy for AKI in pediatric patients.

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

“…The meaning of plasma citrate is not clear enough since both negative and positive correlations with estimated glomerular filtration rate (eGFR) have been proposed [ 51 , 172 ]; in addition, the ratio of myo-inositol:citrate in urine seems to predict active renal vasculitis [ 173 ]. Similarly, in AKI pediatric patients, urinary citrate levels were found to be reduced [ 174 ]. In RCC, citrate levels decreased in urine [ 175 ], but these are enriched in tissue [ 62 ].…”

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

“…Non-invasively collected urine and fecal samples are considered the most suitable biological substrates for deciphering the relationship between diet and nutritionally driven metabolic changes in groups of breastfed (BF) and formula-fed (FF) newborns, as they represent the final points of gut microbial metabolism occurring inside human intestinal tract (feces) and of the excreted metabolites produced by the host (urine) [ 46 ]. Apart from reflecting nutritional metabolic changes, NMR urine metabolomics progressively find their place as a diagnostic tool for neonatal morbidities involving renal function and food intolerance, namely acute kidney injury (AKI) and necrotizing enterocolitis (NEC), respectively [ 47 , 48 ]. Metabolites of the biological samples under investigation are analyzed by implementing high-throughput, high-sensitivity and reproducible methodologies, such as GC-FID-, LC-MS- or NMR-targeted and/or untargeted metabolomics to holistically identify biomarkers related to different infant nutritional strategies [ 46 ].…”

New Insights from Metabolomics in Pediatric Renal Diseases

“…In a recent study by Muhle-Goll et al, the diagnostic accuracy of NMR urine metabolite patterns for the diagnosis of neonatal and pediatric AKI according to the kidney disease improving global outcomes (KDIGO) definition was investigated [ 44 ]. A cohort of 65 neonatal and pediatric patients (0–18 years) with established AKI of heterogeneous etiology were compared, both to a group of apparently healthy children (n = 53), and to a group of critically ill children without AKI (n = 31).…”

“…A panel of four metabolites were identified for AKI diagnosis. In particular, urinary citrate levels were significantly reduced, whereas leucine and valine levels were elevated [ 44 ].…”