A urinary fragment of mucin-1 subunit α is a novel biomarker associated with renal dysfunction in the general population

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
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 > Institute of Cardiovascular and Medical Sciences
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
601881HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507RI CARDIOVASCULAR & MEDICAL SCIENCES