{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:05:53Z","timestamp":1792537553716,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Faculty of Medicine, Timi\u0219oara, Romania","award":["6DOC\/2020"],"award-info":[{"award-number":["6DOC\/2020"]}]},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Faculty of Medicine, Timi\u0219oara, Romania","award":["6DOC\/2020"],"award-info":[{"award-number":["6DOC\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) has become one of the most rapidly advancing diseases of the century, contributing significantly to increased mortality and morbidity. Metabolomics presents a promising approach to understanding CKD pathogenesis and identifying novel biomarkers for early diagnosis. This study evaluated serum and urine metabolomic profiles in CKD patients with declining glomerular filtration rates (eGFR). Using targeted metabolomics, we quantified seven potential metabolites in blood and urine samples from 20 healthy individuals and 99 CKD patients staged by eGFR according to the KDIGO guidelines. The analysis was conducted using ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. The metabolites investigated included L-phenylalanine, L-methionine, arginine, indoxyl sulfate, kynurenic acid, and L-acetylcarnitine. Quantitative assessments were performed using pure standards and validated through methods such as the limit of detection (LOD) and limit of quantification (LOQ). The findings identified potential biomarkers for early CKD diagnosis: in serum, L-phenylalanine, L-methionine, arginine, kynurenic acid, and indoxyl sulfate, while L-acetylcarnitine was significant in urine. These biomarkers could provide valuable insights into CKD progression and support in developing more effective diagnostic tools for early intervention.<\/jats:p>","DOI":"10.3390\/ijms26072862","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T10:10:08Z","timestamp":1742551808000},"page":"2862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted Analysis of Serum and Urinary Metabolites for Early Chronic Kidney Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Mihaela-Roxana","family":"Glavan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II\u2014Nephrology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7352-5057","authenticated-orcid":false,"given":"Carmen","family":"Socaciu","sequence":"additional","affiliation":[{"name":"Research Center for Applied Biotechnology and Molecular Therapy BIODIATECH, SC Proplanta, Str. Trifoiului 12G, 400478 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Iulia","family":"Socaciu","sequence":"additional","affiliation":[{"name":"Department of Occupational Health, University of Medicine and Pharmacy \u201cIuliu Ha\u0163ieganu\u201d, Str. Victor Babes 8, 400347 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Milas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II\u2014Nephrology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florica","family":"Gadalean","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II\u2014Nephrology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology, Clinical County Emergency Hospital, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Liviu Rebreanu Ave. No 156, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8724-7142","authenticated-orcid":false,"given":"Maria","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II\u2014Nephrology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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Suppl."},{"key":"ref_3","unstructured":"Official Journal of the International Society of Nephrology (2013). KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, Kidney Disease: Improving Global Outcomes (KDIGO)."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yan, M.-T., Chao, C.-T., and Lin, S.-H. (2021). Chronic Kidney Disease: Strategies to Retard Progression. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810084"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kang, E., Li, Y., Kim, B., Huh, K.Y., Han, M., Ahn, J.-H., Sung, H.Y., Park, Y.S., Lee, S.E., and Lee, S. (2022). Identification of Serum Metabolites for Predicting Chronic Kidney Disease Progression According to Chronic Kidney Disease Cause. Metabolites, 12.","DOI":"10.3390\/metabo12111125"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/ckj\/sfx023","article-title":"Clinical Proteomics in Kidney Disease as an Exponential Technology: Heading towards the Disruptive Phase","volume":"10","author":"Sanz","year":"2017","journal-title":"Clin. Kidney J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cca.2013.03.033","article-title":"Metabolomics in Chronic Kidney Disease","volume":"422","author":"Zhao","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ene, C.D., Penescu, M., Nicolae, I., and Capusa, C. (2024). The Role of the L-Arginine\u2013Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease. J. Pers. Med., 14.","DOI":"10.3390\/jpm14030299"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1007\/s00726-017-2494-2","article-title":"The Role of Methionine on Metabolism, Oxidative Stress, and Diseases","volume":"49","author":"Li","year":"2017","journal-title":"Amino Acids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00216-023-05091-x","article-title":"Investigation of Metabolite Alterations in the Kidneys of Methionine-Choline-Deficient Mouse by Mass Spectrometry Imaging","volume":"416","author":"Wang","year":"2024","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mahbub, M.H., Yamaguchi, N., Takahashi, H., Hase, R., Yamamoto, H., Kikuchi, S., and Tanabe, T. (2019). Relationship of Reduced Glomerular Filtration Rate with Alterations in Plasma Free Amino Acids and Uric Acid Evaluated in Healthy Control and Hypertensive Subjects. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-46598-7"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chen, W., Feng, J., Ji, P., Liu, Y., Wan, H., and Zhang, J. (2023). Association of Hyperhomocysteinemia and Chronic Kidney Disease in the General Population: A Systematic Review and Meta-Analysis. BMC Nephrol., 24.","DOI":"10.1186\/s12882-023-03295-y"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1681\/ASN.V111134","article-title":"Serum Total Homocysteine and Cardiovascular Disease Occurrence in Chronic, Stable Renal Transplant Recipients","volume":"11","author":"Ducloux","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, H., Jang, H.B., Yoo, M.-G., Park, S.I., and Lee, H.-J. (2020). Amino Acid Metabolites Associated with Chronic Kidney Disease: An Eight-Year Follow-Up Korean Epidemiology Study. Biomedicines, 8.","DOI":"10.3390\/biomedicines8070222"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e000877","DOI":"10.1136\/bmjdrc-2019-000877","article-title":"Plasma Phenylalanine and Tyrosine and Their Interactions with Diabetic Nephropathy for Risk of Diabetic Retinopathy in Type 2 Diabetes","volume":"8","author":"Luo","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1159\/000519811","article-title":"The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease","volume":"52","author":"Wee","year":"2021","journal-title":"Am. J. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wirthgen, E., Hoeflich, A., Rebl, A., and G\u00fcnther, J. (2018). Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01957"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"sfad248","DOI":"10.1093\/ckj\/sfad248","article-title":"Study of the Association between Serum Levels of Kynurenine and Cardiovascular Outcomes and Overall Mortality in Chronic Kidney Disease","volume":"17","author":"Larabi","year":"2024","journal-title":"Clin. Kidney J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"McCann, M.R., George De la Rosa, M.V., Rosania, G.R., and Stringer, K.A. (2021). L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine. Metabolites, 11.","DOI":"10.3390\/metabo11010051"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12986-018-0328-1","article-title":"Plasma Acylcarnitines Could Predict Prognosis and Evaluate Treatment of IgA Nephropathy","volume":"16","author":"Xia","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"MS663001","DOI":"10.2739\/kurumemedj.MS663001","article-title":"Kinetics of Serum Carnitine Fractions in Patients with Chronic Kidney Disease Not on Dialysis","volume":"66","author":"Yano","year":"2019","journal-title":"Kurume Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Glavan, M.-R., Socaciu, C., Socaciu, A.I., Gadalean, F., Cretu, O.M., Vlad, A., Muntean, D.M., Bob, F., Milas, O., and Suteanu, A. (2023). Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041057"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-8981(03)00338-3","article-title":"Serum Concentrations of Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginine in Patients with Chronic Kidney Diseases","volume":"336","author":"Fleck","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Trabado, S., Al-Salameh, A., Croixmarie, V., Masson, P., Corruble, E., F\u00e8ve, B., Colle, R., Ripoll, L., Walther, B., and Boursier-Neyret, C. (2017). The Human Plasma-Metabolome: Reference Values in 800 French Healthy Volunteers; Impact of Cholesterol, Gender and Age. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173615"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s41100-018-0195-2","article-title":"Oxidative Stress in Chronic Kidney Disease","volume":"4","author":"Ling","year":"2018","journal-title":"Ren. Replace. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0008-6363(01)00340-6","article-title":"Regulation of Mesangial Cell Function by Vasodilatory Signaling Molecules","volume":"51","author":"Buschhausen","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hu, Y., and Jiang, W. (2024). Mannose and Glycine: Metabolites with Potentially Causal Implications in Chronic Kidney Disease Pathogenesis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0298729"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2801S","DOI":"10.1093\/jn\/134.10.2801S","article-title":"Role of L-Arginine in the Pathogenesis and Treatment of Renal Disease","volume":"134","author":"Cherla","year":"2004","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"F1855","DOI":"10.1152\/ajprenal.00025.2018","article-title":"Arginine Reprogramming in ADPKD Results in Arginine-Dependent Cystogenesis","volume":"315","author":"Trott","year":"2018","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2215\/CJN.06000613","article-title":"Plasma and Urinary Amino Acid Metabolomic Profiling in Patients with Different Levels of Kidney Function","volume":"9","author":"Duranton","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xie, T., Yao, L., and Li, X. (2024). Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases. Antioxidants, 13.","DOI":"10.3390\/antiox13060659"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"390","DOI":"10.22159\/ajpcr.2018.v11i5.24432","article-title":"Assessment of The Potential Role of L- Methionine on Nickel Sulfate Induced Renal Injury and Oxidative Stress in Rat","volume":"11","author":"Bouhalit","year":"2018","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1182\/blood-2015-01-544676","article-title":"Regulation of Thrombosis and Vascular Function by Protein Methionine Oxidation","volume":"125","author":"Gu","year":"2015","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"625","DOI":"10.51620\/0869-2084-2022-67-11-625-632","article-title":"Methionine and Total Homocysteine in Hypertensive Patients with Renal Excretory Dysfunction","volume":"67","author":"Zhloba","year":"2022","journal-title":"Russ. Clin. Lab. Diagn."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643","DOI":"10.5607\/en.2019.28.6.643","article-title":"Autophagy, Cellular Aging and Age-Related Human Diseases","volume":"28","author":"Cheon","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114493","DOI":"10.1016\/j.celrep.2024.114493","article-title":"Mitochondrial Perturbations in Low-Protein-Diet-Fed Mice Are Associated with Altered Neutrophil Development and Effector Functions","volume":"43","author":"Thind","year":"2024","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/ndt\/gfl044","article-title":"Why Is Homocysteine Elevated in Renal Failure and What Can Be Expected from Homocysteine-Lowering?","volume":"21","year":"2006","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Takahashi, R., Kanda, T., Komatsu, M., Itoh, T., Minakuchi, H., Urai, H., Kuroita, T., Shigaki, S., Tsukamoto, T., and Higuchi, N. (2022). The Significance of NAD\u2009+\u2009Metabolites and Nicotinamide N-Methyltransferase in Chronic Kidney Disease. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-10476-6"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1590\/2175-8239-jbn-2018-0214","article-title":"Dietary Intake of Tyrosine and Phenylalanine, and p-Cresyl Sulfate Plasma Levels in Non-Dialyzed Patients with Chronic Kidney Disease","volume":"42","author":"Fernandes","year":"2020","journal-title":"Braz. J. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1073\/pnas.97.3.1242","article-title":"The Kidney Is an Important Site for in Vivo Phenylalanine-to-Tyrosine Conversion in Adult Humans: A Metabolic Role of the Kidney","volume":"97","author":"Meek","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Singh, V., Rai, R.K., Arora, A., Sinha, N., and Thakur, A.K. (2014). Therapeutic Implication of L-Phenylalanine Aggregation Mechanism and Its Modulation by D-Phenylalanine in Phenylketonuria. Sci. Rep., 4.","DOI":"10.1038\/srep03875"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Balint, L., Socaciu, C., Socaciu, A.I., Vlad, A., Gadalean, F., Bob, F., Milas, O., Cretu, O.M., Suteanu-Simulescu, A., and Glavan, M. (2023). Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients. Biomolecules, 13.","DOI":"10.3390\/biom13071086"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/ndt\/gfn739","article-title":"Increased Indoleamine 2,3-Dioxygenase (IDO) Activity and Elevated Serum Levels of Tryptophan Catabolites in Patients with Chronic Kidney Disease: A Possible Link between Chronic Inflammation and Uraemic Symptoms","volume":"24","author":"Schefold","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1038\/sj.bjp.0703250","article-title":"Role of Kynurenines in the Neurotoxic Actions of Kainic Acid","volume":"129","author":"Behan","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/geroni\/igy023.377","article-title":"Kynurenic Acid a Tryptophan Metabolite Induces Bone Loss in Mice","volume":"2","author":"Isales","year":"2018","journal-title":"Innov. Aging"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ballesteros, J., Rivas, D., and Duque, G. (2023). The Role of the Kynurenine Pathway in the Pathophysiology of Frailty, Sarcopenia, and Osteoporosis. Nutrients, 15.","DOI":"10.20944\/preprints202305.1990.v1"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Aregger, F., Uehlinger, D.E., Fusch, G., Bahonjic, A., Pschowski, R., Walter, M., and Schefold, J.C. (2018). Increased Urinary Excretion of Kynurenic Acid Is Associated with Non-Recovery from Acute Kidney Injury in Critically Ill Patients. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-0841-5"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/toxsci\/kfq024","article-title":"Kynurenic Acid Is a Potent Endogenous Aryl Hydrocarbon Receptor Ligand That Synergistically Induces Interleukin-6 in the Presence of Inflammatory Signaling","volume":"115","author":"DiNatale","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s00018-020-03645-1","article-title":"Gut Microbiota-Derived Tryptophan Metabolism Mediates Renal Fibrosis by Aryl Hydrocarbon Receptor Signaling Activation","volume":"78","author":"Liu","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, W.-C., Tomino, Y., and Lu, K.-C. (2018). Impacts of Indoxyl Sulfate and P-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120. Toxins, 10.","DOI":"10.3390\/toxins10090367"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/ki.2013.497","article-title":"Uremic solutes and risk of end-stage renal disease in type 2 diabetes: Metabolomic study","volume":"85","author":"Niewczas","year":"2014","journal-title":"Kidney Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tvjl.2017.12.011","article-title":"Plasma Indoxyl Sulfate Concentration Predicts Progression of Chronic Kidney Disease in Dogs and Cats","volume":"232","author":"Chen","year":"2018","journal-title":"Vet. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2016.6665","article-title":"Oxidant Mechanisms in Renal Injury and Disease","volume":"25","author":"Ratliff","year":"2016","journal-title":"Antioxid. Redox Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"C685","DOI":"10.1152\/ajpcell.00236.2012","article-title":"CREB, NF-\u039aB, and NADPH Oxidase Coordinately Upregulate Indoxyl Sulfate-Induced Angiotensinogen Expression in Proximal Tubular Cells","volume":"304","author":"Shimizu","year":"2013","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lano, G., Burtey, S., and Sall\u00e9e, M. (2020). Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins, 12.","DOI":"10.3390\/toxins12040229"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1113\/jphysiol.2006.125799","article-title":"New Insights Concerning the Role of Carnitine in the Regulation of Fuel Metabolism in Skeletal Muscle","volume":"581","author":"Stephens","year":"2007","journal-title":"J. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3164\/jcbn.15-146","article-title":"Retention of Acetylcarnitine in Chronic Kidney Disease Causes Insulin Resistance in Skeletal Muscle","volume":"59","author":"Miyamoto","year":"2016","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.toxlet.2016.02.018","article-title":"Characterization of Urinary Metabolites as Biomarkers of Colistin-Induced Nephrotoxicity in Rats by a Liquid Chromatography\/Mass Spectrometry-Based Metabolomics Approach","volume":"248","author":"Jeong","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Besouw, M., Cornelissen, E., Cassiman, D., Kluijtmans, L., van den Heuvel, L., and Levtchenko, E. (2014). Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome Due to Cystinosis, Springer.","DOI":"10.1007\/8904_2014_312"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ekir.2016.12.003","article-title":"Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals with Type 2 Diabetes and Kidney Disease","volume":"2","author":"Liu","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"819","DOI":"10.2337\/db18-0090","article-title":"Proximal Tubular Cell\u2013Specific Ablation of Carnitine Acetyltransferase Causes Tubular Disease and Secondary Glomerulosclerosis","volume":"68","author":"Kruger","year":"2019","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1038\/s41467-019-09329-0","article-title":"Identification of Serum Metabolites Associating with Chronic Kidney Disease Progression and Anti-Fibrotic Effect of 5-Methoxytryptophan","volume":"10","author":"Chen","year":"2019","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/2862\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:58:02Z","timestamp":1760029082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/2862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26072862"],"URL":"https:\/\/doi.org\/10.3390\/ijms26072862","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]}}}