ArticleKidney international reports2019
Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis.
Article in Kidney international reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study.Scientific reports · 2023Pooled it
- Urinary proteomic profiling to identify early biomarkers of non-diabetic chronic kidney disease.Clinical kidney journal · 2025Article
- Elevated isoleucine may be a protective factor for primary hypertension: A pooled causal effect study.Medicine · 2025Article
- Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency.Renal failure · 2024Article
- Epigenetics of Hypertensive Nephropathy.Biomedicines · 2024Review
- Renal Epithelial Mitochondria: Implications for Hypertensive Kidney Disease.Comprehensive Physiology · 2023Article
- RNA sequencing reveals the mechanism of FTO in inhibiting inflammation and excessive proliferation of lipopolysaccharide-induced human glomerular mesangial cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Untargeted Metabolite Profiling of Adipose Tissue in Rats Exposed to Mepiquat.Foods (Basel, Switzerland) · 2023Article
- Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children.Nutrients · 2023Article
- Amino Acid Profiles and Nutritional Evaluation of Fresh Sweet-Waxy Corn from Three Different Regions of China.Nutrients · 2022Article
- Influence of Genetic West African Ancestry on Metabolomics among Hypertensive Patients.Metabolites · 2022Article
- Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension.Metabolites · 2022Article
- Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses.Chemical research in toxicology · 2022Article
- Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract fromPharmaceutical biology · 2021Article
- Renal metabolism and hypertension.Nature communications · 2021Review
- The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease.American journal of nephrology · 2021Review
- Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.BMC medical genomics · 2020Article
- Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia.Acta pharmaceutica Sinica. B · 2020Article
- Introducing Serine as Cardiovascular Disease Biomarker Candidate via Pathway Analysis.Galen medical journal · 2020Article
- Metabolomics biotechnology, applications, and future trends: a systematic review.RSC advances · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
introductionHypertensive 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.
methodsWe 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.
resultsAmino 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.
conclusionEarly 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.
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