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Identification of a urine metabolomic signature in patients with advanced-stage chronic kidney disease
Open accessAbstract
The prevalence of chronic kidney disease (CKD) is increasing and frequently progresses to end-stage renal disease. There is an urgent demand to discover novel markers of disease that allow monitoring disease progression and, eventually, response to treatment. To identify such markers, and as a proof of principle, we determined if a metabolite signature corresponding to CKD can be found in urine. In the discovery stage, we analyzed the urine metabolome by NMR of 15 patients with CKD and compared that with the metabolome of 15 healthy individuals and found a classification pattern clearly indicative of CKD. A validation cohort of urine samples from an additional 16 patients with CKD and 15 controls was then analyzed by (Selected Reaction Monitoring) liquid chromatography-triple quadrupole mass spectrometry and indicated that a group of seven urinary metabolites differed between CKD and non-CKD urine samples. This profile consisted of 5-oxoproline, glutamate, guanidoacetate, α-phenylacetylglutamine, taurine, citrate, and trimethylamine N-oxide. Thus, we identified a panel of urine metabolites differentially present in urine that may help identify and monitor patients with CKD.
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“Metabolomic analysis of urine from 31 patients identified a group of seven metabolites that differed between chronic kidney disease (CKD) and non-CKD urine samples; TMAO concentrations in plasma were higher in CKD (92).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [92]
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Cites
Regulation of glutathione synthesis
Lu, S. C.-L. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.05.005 · Cited by 2,131
Selected reaction monitoring for quantitative proteomics: a tutorial
Lange, V., Picotti, P., Domon, B., & Aebersold, R. H. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.61 · Cited by 1,396
Biomarkers in chronic kidney disease: a review
Fassett, R. G., Venuthurupalli, S. K., Gobe, G. C., Coombes, J. S., Cooper, M. A., & Hoy, W. E. (2011) · Kidney International · doi:10.1038/ki.2011.198 · Cited by 466
Phisitkul, S., Khanna, A., Simoni, J. M., Broglio, K. R., Sheather, S. J., Rajab, M. H., & Wesson, D. E. (2010) · Kidney International · doi:10.1038/ki.2009.519 · Cited by 287
Bain, M. A., Faull, R., Fornasini, G., Milne, R. W., & Evans, A. M. (2006) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfk056 · Cited by 282
Metabolomics in the study of kidney diseases
Weiss, R. H., & Kim, K. (2011) · Nature Reviews Nephrology · doi:10.1038/nrneph.2011.152 · Cited by 265
Role of glutamine in human carbohydrate metabolism in kidney and other tissues
Stümvoll, M., Perriello, G., Meyer, C., & Gerich, J. E. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.055003778.x · Cited by 230
Lauridsen, M. B., Hansen, S. H., Jaroszewski, J. W., & Cornett, C. (2007) · Analytical Chemistry · doi:10.1021/ac061354x · Cited by 179
Phenylacetylglutamine May Replace Urea as a Vehicle for Waste Nitrogen Excretion
Brusilow, S. W. (1991) · Pediatric Research · doi:10.1203/00006450-199102000-00009 · Cited by 173
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Zahid, S., Dafré, A. L., Currais, A. J. M., Yu, J., Schubert, D. A., & Maher, P. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076828 · Cited by 13
Gill, D., Zagkos, L., Gill, R., Benzing, T. R., Jordan, J., Birkenfeld, A. L., Burgess, S., & Zahn, G. (2023) · BMC Medicine · doi:10.1186/s12916-023-03227-5 · Cited by 11
Metabolómica de la nefropatía diabética: tras la huella de indicadores de desarrollo y progresión
Cordero‐Pérez, P., Sánchez‐Martínez, C., García-Hernández, P. A., & Saucedo, A. L. (2020) · Nefrología · doi:10.1016/j.nefro.2020.07.002 · Cited by 12
Heynen, J. P., McHugh, R., Boora, N. S., Simcock, G. P., Kildea, S. V., Austin, M., Laplante, D. P., King, S., Montina, T., & Metz, G. A. S. (2023) · Metabolites · doi:10.3390/metabo13040579 · Cited by 11
Mogos, M., Socaciu, C., Socaciu, A. I., Vlad, A., Gădălean, F., Bob, F. R., Milas, L. O., Cretu, O. M., Suteanu‐Simulescu, A., Glavan, M., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11061527 · Cited by 11
Trimethylamine-N-Oxide (TMAO) and Predicted Risk of Cardiovascular Events After Partial Nephrectomy
Zou, X., Xiong, L., Guo, Z., Li, Y., Kang, N., Liu, X., Xie, Y., Peng, Y., Liu, Y., Cai, X., et al. (2022) · Asian Journal of Surgery · doi:10.1016/j.asjsur.2023.08.104 · Cited by 11
Advances in the Detection, Mechanism and Therapy of Chronic Kidney Disease
Dong, Y. J., Qu, X., Wu, G., Luo, X., Tang, B., Wu, F., Fan, L., Sooranna, D., & Liang, T. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191119094354 · Cited by 11
Han, K. H., Kim, B., Ji, S. C., Kang, H. G., Cheong, H. I., Cho, J., & Ha, I. S. (2020) · Metabolites · doi:10.3390/metabo10040169 · Cited by 11
Pavlaki, A., Begou, O., Deda, O., Farmaki, E., Dotis, J., Gika, H., Ταπάρκου, Ά., Raikos, Ν., Papachristou, F., Theodoridis, G. A., et al. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00855 · Cited by 11
Martin‐Lorenzo, M., Ramos-Barron, M. A., Gutierrez-Garcia, P., Martín-Blázquez, A., Santiago‐Hernandez, A., Rodrigo, E., Gómez-Alamillo, C., & Álvarez‐Llamas, G. (2021) · Antioxidants · doi:10.3390/antiox10060896 · Cited by 11
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Kim, Y., Xu, W., Barrs, V. R., Beatty, J. A., & Kenéz, Á. (2022) · Metabolomics · doi:10.1007/s11306-022-01877-9 · Cited by 9
The urinary metabolome of chronic kidney disease
Pallet, N., Thervet, É., Beaune, P. H., Karras, A., & Bertho, G. (2014) · Kidney International · doi:10.1038/ki.2014.34 · Cited by 9
Gut microbiota and renal fibrosis
Tong, Y., Guo, S., Li, T., Yang, K., Gao, W., Peng, F., & Zou, X. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123072 · Cited by 8
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Yi, H.-M., Won, S., Pak, J., Park, S.-E., Kim, M.-R., Kim, J.-H., Park, E. Y., Hwang, S., Lee, M., Son, H.-S., et al. (2025) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2411.11071 · Cited by 8
Cordero‐Pérez, P., Sánchez‐Martínez, C., García-Hernández, P. A., & Saucedo, A. L. (2020) · Nefrología (English Edition) · doi:10.1016/j.nefroe.2020.12.002 · Cited by 8
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Blazquez‐Navarro, A., Bauer, C., Wittenbrink, N., Wolk, K., Sabat, R., Dang‐Heine, C., Neumann, S., Roch, T., Wehler, P., Blazquez‐Navarro, R., et al. (2022) · Current Research in Translational Medicine · doi:10.1016/j.retram.2022.103334 · Cited by 8
Haonon, O., Liu, Z., Dangtakot, R., Pinlaor, P., Puapairoj, A., Cha’on, U., Intuyod, K., Pongking, T., Jantawong, C., Sengthong, C., et al. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109053 · Cited by 7
Sánchez-Niño, M. D., & Ortíz, A. (2014) · Clinical Kidney Journal · doi:10.1093/ckj/sfu099 · Cited by 8
Ribeiro, S. A., Braga, E. L. R., Queiroga, M. L., Clementino, M., Fonseca, X. M. Q. C., Belém, M. O., Magalhães, L. M. V. C., de Sousa, J. K., Freitas, T. M., Veras, H. N., et al. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.02.001 · Cited by 7
Humphries, T. L. R., Vesey, D. A., Galloway, G. J., Gobe, G. C., & Francis, R. S. (2023) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2023.04.001 · Cited by 6
Lei, Y., Jiang, J., Chen, L., Fang, Q., Li, C., Fei, Y., Qu, S., Xia, Z., Ning, Y., He, M., et al. (2025) · BMC Nephrology · doi:10.1186/s12882-025-04625-y · Cited by 5
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Moritz, L., Schumann, A., Pöhl, M., Köttgen, A., Hannibal, L., & Spiekerkoetter, U. (2023) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2023.110703 · Cited by 5
Braga, P. C., Guerra‐Carvalho, B., Almeida, M., Pereira, S. S., Oliveira, P. F., Alves, M. G., & Rodrigues, A. S. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.112215 · Cited by 5
Metabolomics tools for biomarker discovery: applications in chronic kidney disease
Cuevas-Delgado, P., Miguel, V., Lamas, S., & Barbas, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822859-3.00013-4 · Cited by 5
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Klemens, C. A., Fedoriuk, M., Semenikhina, M., Stefanenko, M., Zietara, A. P., Levchenko, V., Dissanayake, L. V., Palygin, O., & Staruschenko, A. (2025) · Communications Biology · doi:10.1038/s42003-025-07631-w · Cited by 4
Méndez‐Rodríguez, K. B., Ramírez-Gómez, L. M., Ilizaliturri-Hernandez, C. A., Borjas‐García, J. A., Saldaña-Villanueva, K., & Pérez‐Vázquez, F. J. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120205 · Cited by 4
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Self-citationLin, K., Xiong, L., Zhang, W., Chen, X., Zhu, J., Li, X., & Zhang, J. (2024) · Journal of Chromatography B · doi:10.1016/j.jchromb.2024.124358 · Cited by 3
Durán, Á., Ramiro-Alcobendas, J.-L., Duque, F. J., Nicolás-Barceló, P., Cristóbal, J. I., Ruíz-Tapia, P., Barrera‐Chacon, R., & Marcos, C. F. (2025) · Veterinary and Animal Science · doi:10.1016/j.vas.2025.100440 · Cited by 3
Trujillo‐Gonzalez, I., & Zeisel, S. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-66162-1.00018-4 · Cited by 3
Taha, K., Sharma, A., Kroeker, K., Ross, C. J., Carleton, B., Wishart, D. S., Medeiros-Domingo, M., & Blydt‐Hansen, T. D. (2022) · Pediatric Transplantation · doi:10.1111/petr.14460 · Cited by 3
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Kouidhi, S., Souai, N., Alhujaily, M. M., Zidi, O., Kochbati, A., Redissi, A., Belali, T. M., Kossai, I. E., Manaa, J. E., Cherif, A., et al. (2021) · Diagnostics · doi:10.3390/diagnostics11060962 · Cited by 2
Mansour, N. Y., Ismail, M. F., Sayed, N. H., El-Ansary, A. R., & Mohanad, M. (2026) · Scientific Reports · doi:10.1038/s41598-026-44271-4 · Cited by 1
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Christians, U., Klawitter, J., Klepacki, J., & Klawitter, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803014-1.00003-0 · Cited by 1
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Gill, D., Zagkos, L., Gill, R., Benzing, T. R., Jordan, J., Birkenfeld, A. L., Burgess, S., & Zahn, G. (2023) · medRxiv · doi:10.1101/2023.08.29.23294760 · Cited by 1
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Álvarez‐Llamas, G., Barderas, M. G., Posada-Ayala, M., Martin‐Lorenzo, M., & Vivanco, F. (2014) · Comprehensive analytical chemistry · doi:10.1016/b978-0-444-62650-9.00011-7
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Fernandes, M., Cisek, K. K., & Husi, H. (2018) · doi:10.1002/9781119183952.ch20
Ortíz, A. (2018) · doi:10.1002/9781119183952.ch19
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Shankar Ganesh, M., Aravindhan, S., & Satheesh, S. (2024) · Research Square · doi:10.21203/rs.3.rs-4006719/v1
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Metadata
- Authors
- Posada-Ayala, M., Zubiri, I., Martin-Lorenzo, M., Sanz-Maroto, A., Molero, D., Gonzalez-Calero, L., Fernandez-Fernandez, B., de la Cuesta, F., Laborde, C. M., Barderas, M. G., Ortiz, A., Vivanco, F., & Alvarez-Llamas, G.
- Affiliations
- Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ES)
- Universidad Complutense de Madrid (ES)
- Servicio de Salud de Castilla La Mancha (ES)
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 85
- Issue
- 1
- Pages
- 103-111
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2053835433
- Cited by
- 167
- References
- 22
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 13 · 2022: 14 · 2021: 11 · 2020: 24 · 2019: 15 · 2018: 14 · 2017: 15 · 2016: 16 · 2015: 10 · 2014: 10
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Hispana (submittedVersion)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- chronic kidney disease, urine metabolomics, metabolomic signatures, biomarkers, disease progression monitoring, pyroglutamic acid, glutamate, taurine, citrate, trimethylamine N-oxide, NMR metabolomics, multiple reaction monitoring
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Mass Spectrometry, Cohort Studies, Biomarkers, Case-Control Studies, Metabolome
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