Kidney International Reports (Sep 2017)

A Urinary Fragment of Mucin-1 Subunit α Is a Novel Biomarker Associated With Renal Dysfunction in the General Population

  • Zhen-Yu Zhang,
  • Susana Ravassa,
  • Martin Pejchinovski,
  • Wen-Yi Yang,
  • Petra Zürbig,
  • Begoña López,
  • Fang-Fei Wei,
  • Lutgarde Thijs,
  • Lotte Jacobs,
  • Arantxa González,
  • Jens-Uwe Voigt,
  • Peter Verhamme,
  • Tatiana Kuznetsova,
  • Javier Díez,
  • Harald Mischak,
  • Jan A. Staessen

DOI
https://doi.org/10.1016/j.ekir.2017.03.012
Journal volume & issue
Vol. 2, no. 5
pp. 811 – 820

Abstract

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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.

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