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Urine metabolomics insight into acute kidney injury point to oxidative stress disruptions in energy generation and H 2 S availability
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نویسنده
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Gonzalez-Calero Laura ,Ramos-Barron Angeles ,Sanchez-Niño Maria D. ,Gomez-Alamillo Carlos ,García-Segura Juan Manuel ,Ortiz Alberto ,Arias Manuel ,Vivanco Fernando ,Alvarez-Llamas Gloria ,Martin-Lorenzo Marta
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منبع
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journal of molecular medicine - 2017 - دوره : 95 - شماره : 12 - صفحه:1399 -1409
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چکیده
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Acute kidney injury (aki) is one of the main complications in acute care medicine and a risk factor for chronic kidney disease (ckd). aki incidence has increased; however, its diagnosis has limitations and physiopathological mechanisms are underexplored. we investigated urine samples, aiming to identify major metabolite changes during human aki evolution. metabolic signatures found were further explored for a potential link to severity of injury. twenty-four control subjects and 38 hospitalized patients with aki were recruited and urine samples were collected at the time of diagnosis, during follow-up and at discharge. nuclear magnetic resonance (nmr) was used in a first discovery phase for identifying potential metabolic differences. target metabolites of interest were confirmed by liquid chromatography-mass spectrometry (lc-ms/ms) in an independent group. underlying metabolic defects were further explored by kidney transcriptomics of murine toxic aki. urinary 2-hydroxybutyric acid, pantothenic acid, and hippuric acid were significantly downregulated and urinary n-acetylneuraminic acid, phosphoethanolamine, and serine were upregulated during aki. hippuric acid, phosphoethanolamine, and serine showed further downregulation/upregulation depending on the metabolite in acute tubular necrosis (atn) aki compared to prerenal aki. kidney transcriptomics disclosed decreased expression of cystathionase, cystathionine-β-synthase, and ethanolamine-phosphate cytidylyltransferase, and increased n-acetylneuraminate synthase as the potentially underlying cause of changes in urinary metabolites. a urinary metabolite panel identified aki patients and provided insight into intrarenal events. a urine fingerprint made up of six metabolites be related to pathophysiological changes in oxidative stress, energy generation, and h2s availability associated with aki.
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کلیدواژه
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Metabolomics ,Urine ,Acute kidney injury ,Oxidative stress ,H2S
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آدرس
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Department of Immunology, Spain, Universidad de Cantabria, Nephrology Department, Spain, Department of Nephrology/IRSIN, Spain, Universidad de Cantabria, Nephrology Department, Spain, Universidad Complutense, Department of Biochemistry and Molecular Biology I, Spain, Department of Nephrology/IRSIN, Spain, Universidad de Cantabria, Nephrology Department, Spain, Department of Immunology, Spain. Universidad Complutense, Department of Biochemistry and Molecular Biology I, Spain, Department of Immunology, Spain, Department of Immunology, Spain
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Authors
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