ArticleEBioMedicine2017
Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 147 citations in OpenAlex.
- Urine tricarboxylic acid cycle signatures of early-stage diabetic kidney disease.Metabolomics : Official journal of the Metabolomic Society · 2021Trial
- Trial
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- Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.Nature communications · 2026Article
- Association between organophosphorus flame retardant exposure and chronic kidney disease in U.S. adults: NHANES data from 2011 to 2016.European journal of medical research · 2026Article
- Benchmarking the urinary transplant metabolome of kidney transplant recipients using healthy organ donors.Frontiers in transplantation · 2026Article
- Dual effects of fasting on gut microbiota and metabolism: protective adaptation versus barrier dysfunction risks.Frontiers in nutrition · 2026Article
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- Exploring the Effects of Palm Tocotrienol-Rich Fraction in Diabetic Peripheral Neuropathy Rat's Model: An Untargeted Metabolomic Profiling and Correlation Study.International journal of molecular sciences · 2025Article
- The Pathogenesis of Chronic Kidney Disease (CKD) and the Preventive and Therapeutic Effects of Natural Products.Current issues in molecular biology · 2025Review
- Integrative bioinformatics analysis unveils hub transcription factors and their interacting drugs in immunoglobulin A nephropathy: Implications for pathogenesis and treatments.Journal, genetic engineering & biotechnology · 2025Article
- Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD.International journal of molecular sciences · 2025Article
- The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases.Archives of toxicology · 2025Review
- Nuclear Receptor-Targeted Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of drug discovery and pharmacology · 2025Article
- Metabolomics for the Identification of Biomarkers in Kidney Diseases.Nanotheranostics · 2025Review
- Metabolomic and transcriptomic insights into the mechanisms of renal ischemia-reperfusion injury progression.Scientific reports · 2024Article
- Multi-Omics Integration With Machine Learning Identified Early Diabetic Retinopathy, Diabetic Macula Edema and Anti-VEGF Treatment Response.Translational vision science & technology · 2024Article
- Interplay between the Redox System and Renal Tubular Transport.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy.Kidney international reports · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3-4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range-68% to +113%). Pathway analysis revealed that the citric acid cycle was the most significantly affected, with urinary excretion of citrate, cis-aconitate, isocitrate, 2-oxoglutarate and succinate reduced by 40-68%. Reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. Expression of genes regulating aconitate, isocitrate, 2-oxoglutarate and succinate were significantly reduced in kidney biopsies. We observed increased urine citrate excretion (+74%, p=0.00009) and plasma 2-oxoglutarate concentrations (+12%, p=0.002) in CKD patients during treatment with a vitamin-D receptor agonist in a randomized trial. In conclusion, urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non-diabetic CKD. This supports the emerging view of CKD as a state of mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.