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

Nuclear magnetic resonance spectroscopy (NMR), which simultaneously measures all the small molecules present in a sample provides a great tool for metabolomic analysis. It has been widely used in the identification of disease biomarkers to inform diagnosis and treatment decisions.

A variety of biomarkers have been identified for acute kidney injury (AKI) in several metabolomic studies. Unfortunately, none has shown adequate specificity for kidney injury to be implemented in clinical practice and few clinical studies have conducted metabolomic analysis in pediatric AKI.

AKI is a serious, rapid-onset reduction in kidney function that prevents normal blood homeostasis. The resultant increases in blood levels of waste products and potassium can cause nausea and vomiting, muscle weakness, and heart arrhythmias. It is a common complication among critically ill patients and seriously impedes recovery. Outcomes are particularly poor among pediatric and neonatal patients.

It is important that AKI is diagnosed quickly so the effects can be managed, and morbidity reduced. The current gold standard for diagnosing AKI —serum creatinine levels and urine output measurements—only provides indirect markers of reduced glomerular filtration rate. Consequently, there is a delay before a problem becomes apparent. In addition, they do not provide information regarding the underlying cause of renal impairment.

This unmet need for early diagnosis of AKI was addressed in a recent pediatric study. In order to evaluate whether AKI in neonatal and pediatric patients has a unique urine metabolomic fingerprint, urine samples from neonatal and pediatric patients with established AKI and healthy controls were analyzed by ¹H NMR using a Bruker 600 MHz Avance II spectrometer with a double resonance 5-mm BBI probe.

Four panels of metabolites were found to be indicative of a diagnosis of AKI. ¹H NMR spectra revealed that urinary citrate levels were significantly reduced in patients with AKI, whereas levels of leucine and valine were elevated compared with those in patients without AKI. The researchers found that the metabolite profiles also differed between the various subtypes of AKI with different aetiologies.

Some of the metabolites identified as potential biomarkers for AKI in animal studies (hippurate, indoxylsulfate, creatinine) were found not to differ between healthy patients and patients with AKI. Also, in contrast to some previous reports, the changes in metabolite profiles were similar for neonatal and paediatric patients.

These latest data provide a promising lead for the development of a novel technique for the early identification of patients with AKI. Although further validation in larger studies will be required, it is hoped that the observed differences in metabolite profiles can ultimately be used to improve patient outcomes in AKI. Furthermore, the potential for metabolomic differentiation of AKI subtypes may enable treatment to be tailored according to the underlying cause of AKI.

“In conclusion, this study shows that NMR spectroscopy yields high diagnostic accuracy for AKI in paediatric patients”  published as an MDPI article by “Muhle-Goll C, et al. Int. J. Mol. Sci. 2020;21:1187. https://www.mdpi.com/1422-0067/21/4/1187” 

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