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Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Care | Research

A novel urinary biomarker predicts 1-year mortality after discharge from intensive care

Authors: Esther Nkuipou-Kenfack, Agnieszka Latosinska, Wen-Yi Yang, Marie-Céline Fournier, Alice Blet, Blerim Mujaj, Lutgarde Thijs, Elodie Feliot, Etienne Gayat, Harald Mischak, Jan A. Staessen, Alexandre Mebazaa, Zhen-Yu Zhang, The French and European Outcome Registry in Intensive Care Unit Investigators

Published in: Critical Care | Issue 1/2020

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Abstract

Rationale

The urinary proteome reflects molecular drivers of disease.

Objectives

To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.

Methods

In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses.

Measurements and main results

In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708–0.798) and 0.688 (0.656–0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00–2.91) for ACM128 (+ 1 SD), 1.24 (1.16–1.32) for the Charlson Comorbidity Index (+ 1 point), and ≥ 1.19 (P ≤ 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P ≤ 0.0001) IDI (≥ + 0.50), NRI (≥ + 53.7), and AUC (≥ + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis.

Conclusions

The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.
Appendix
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Metadata
Title
A novel urinary biomarker predicts 1-year mortality after discharge from intensive care
Authors
Esther Nkuipou-Kenfack
Agnieszka Latosinska
Wen-Yi Yang
Marie-Céline Fournier
Alice Blet
Blerim Mujaj
Lutgarde Thijs
Elodie Feliot
Etienne Gayat
Harald Mischak
Jan A. Staessen
Alexandre Mebazaa
Zhen-Yu Zhang
The French and European Outcome Registry in Intensive Care Unit Investigators
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Care
Biomarkers
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2686-0

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