Zhang, Z.-Y. et al. (2017) A urinary fragment of mucin-1 subunit α is a novel biomarker associated with renal dysfunction in the general population. Kidney International Reports, 2(5), pp. 811-820. (doi: 10.1016/j.ekir.2017.03.012) (PMID:28920100) (PMCID:PMC5589115)
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Abstract
Introduction: Sequencing peptides included in the urinary proteome identifies the parent proteins and may reveal mechanisms underlying the pathophysiology of chronic kidney disease. Methods: In 805 randomly recruited Flemish individuals (50.8% women; mean age, 51.1 years), we determined the estimated glomerular filtration rate (eGFR) from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We categorized eGFR according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guideline. We analyzed 74 sequenced urinary peptides with a detectable signal in more than 95% of participants. Follow-up measurements of eGFR were available in 597 participants. Results: In multivariable analyses, baseline eGFR decreased (P ≤ 0.022) with urinary fragments of mucin-1 (standardized association size expressed in ml/min/1.73 m2, −4.48), collagen III (−2.84), and fibrinogen (−1.70) and was bi-directionally associated (P ≤ 0.0006) with 2 urinary collagen I fragments (+2.28 and −3.20). The eGFR changes over 5 years (follow-up minus baseline) resulted in consistent estimates (P ≤ 0.025) for mucin-1 (−1.85), collagen (−1.37 to 1.43) and fibrinogen (−1.45) fragments. Relative risk of having or progressing to eGFR <60 ml/min/1.73 m2 was associated with mucin-1. Partial least-squares analysis confirmed mucin-1 as the strongest urinary marker associated with decreased eGFR, with a score of 2.47 compared with 1.80 for a collagen I fragment as the next contender. Mucin-1 predicted eGFR decline to <60 ml/min/1.73 m2 over and above microalbuminuria (P = 0.011) and retained borderline significance (P = 0.05) when baseline eGFR was accounted for. Discussion: In the general population, mucin-1 subunit α, an extracellular protein that is shed from renal tubular epithelium, is a novel biomarker associated with renal dysfunction.
| Item Type: | Articles |
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| Additional Information: | The European Union (HEALTH-FP7-278249-EUMASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) and The Ministry of Economy and Competitiveness, Madrid, Spain (Carlos III Institute of Health, CIBER-CV CB16/11/00483) currently support this study. |
| Keywords: | Collagen, fibrosis, glomerular filtration rate, mucin-1, population science, proteomics. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Mischak, Professor Harald |
| Authors: | Zhang, Z.-Y., Ravassa, S., Pejchinovski, M., Yang, W.-Y., Zürbig, P., López, B., Wei, F.-F., Thijs, L., Jacobs, L., González, A., Voigt, J.-U., Verhamme, P., Kuznetsova, T., Díez, J., Mischak, H., and Staessen, J. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Kidney International Reports |
| Publisher: | Elsevier |
| ISSN: | 2468-0249 |
| ISSN (Online): | 2468-0249 |
| Published Online: | 07 April 2017 |
| Copyright Holders: | Copyright © 2017 International Society of Nephrology |
| First Published: | First published in Kidney International Reports 2(5): 811-820 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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