Format

Send to

Choose Destination
Kidney Int Rep. 2017 Sep;2(5):811-820. doi: 10.1016/j.ekir.2017.03.012.

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

Author information

1
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
2
Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Navarra Institute for Health Research, Pamplona, Spain.
3
CIBERCV, Carlos III Institute of Health, Madrid, Spain.
4
Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany.
5
Research Unit Cardiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
6
Centre for Molecular and Vascular Biology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
7
Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain.
8
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
9
R&D Group VitaK, Maastricht University, Maastricht, The Netherlands.

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.

KEYWORDS:

collagen; fibrosis; glomerular filtration rate; mucin-1; population science; proteomics

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center