title: Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology.
abstract: Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called "omics" allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.
authors.affiliation: Department of Laboratory Medicine, IRCCS San Martino-IST, University Hospital, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mussap
authors.affiliation: Department of Pediatrics and Clinical Medicine, Section of Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Mista and University of Cagliari, 09042 Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Noto
authors.affiliation: Department of Pediatrics and Clinical Medicine, Section of Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Mista and University of Cagliari, 09042 Cagliari, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Fanos
authors.affiliation: Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Van Den Anker
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000652:urine*; D055432:Metabolomics; D009359:Neonatology / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus