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dc.contributor.authorØvrehus, Marius Altern
dc.contributor.authorBruheim, Per
dc.contributor.authorJu, Wenjun
dc.contributor.authorZelnick, Leila R.
dc.contributor.authorLanglo, Knut Asbjørn Rise
dc.contributor.authorSharma, Kumar
dc.contributor.authorde Boer, Ian H.
dc.contributor.authorHallan, Stein
dc.identifier.citationKidney International Reports. 2019, 4 (2), 321-333.nb_NO
dc.description.abstractIntroduction Hypertensive nephrosclerosis is among the leading causes of end-stage renal disease, but its pathophysiology is poorly understood. We wanted to explore early metabolic changes using gene expression and targeted metabolomics analysis. Methods We analyzed gene expression in kidneys biopsied from 20 patients with nephrosclerosis and 31 healthy controls with an Affymetrix array. Thirty-one amino acids were measured by liquid chromatography coupled with mass spectrometry (LC-MS) in urine samples from 62 patients with clinical hypertensive nephrosclerosis and 33 age- and sex-matched healthy controls, and major findings were confirmed in an independent cohort of 45 cases and 15 controls. Results Amino acid catabolism and synthesis were strongly underexpressed in hypertensive nephrosclerosis (13- and 7-fold, respectively), and these patients also showed gene expression patterns indicating decreased fatty acid oxidation (12-fold) and increased interferon gamma (10-fold) and cellular defense response (8-fold). Metabolomics analysis revealed significant distribution differences in 11 amino acids in hypertensive nephrosclerosis, among them tyrosine, phenylalanine, dopamine, homocysteine, and serine, with 30% to 70% lower urine excretion. These findings were replicated in the independent cohort. Integrated gene-metabolite pathway analysis showed perturbations of renal dopamine biosynthesis. There were also significant differences in homocysteine/methionine homeostasis and the serine pathway, which have strong influence on 1-carbon metabolism. Several of these disturbances could be interconnected through reduced regeneration of tetrahydrofolate and tetrahydrobiopterin. Conclusion Early hypertensive nephrosclerosis showed perturbations of intrarenal biosynthesis of dopamine, which regulates natriuresis and blood pressure. There were also disturbances in serine/glycine and methionine/homocysteine metabolism, which may contribute to endothelial dysfunction, atherosclerosis, and renal fibrosis.nb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleGene expression studies and targeted metabolomics reveal disturbed serine, methionine, and tyrosine metabolism in early hypertensive nephrosclerosisnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalKidney International Reportsnb_NO
dc.description.localcodeª2018 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameMedisinsk klinikk
cristin.unitnameInstitutt for bioteknologi og matvitenskap

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal