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A novel urinary biomarker predicts 1-year mortality after discharge from intensive care
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 spectro...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953276/ https://www.ncbi.nlm.nih.gov/pubmed/31918764 http://dx.doi.org/10.1186/s13054-019-2686-0 |
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author | Nkuipou-Kenfack, Esther Latosinska, Agnieszka Yang, Wen-Yi Fournier, Marie-Céline Blet, Alice Mujaj, Blerim Thijs, Lutgarde Feliot, Elodie Gayat, Etienne Mischak, Harald Staessen, Jan A. Mebazaa, Alexandre Zhang, Zhen-Yu |
author_facet | Nkuipou-Kenfack, Esther Latosinska, Agnieszka Yang, Wen-Yi Fournier, Marie-Céline Blet, Alice Mujaj, Blerim Thijs, Lutgarde Feliot, Elodie Gayat, Etienne Mischak, Harald Staessen, Jan A. Mebazaa, Alexandre Zhang, Zhen-Yu |
author_sort | Nkuipou-Kenfack, Esther |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6953276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69532762020-01-14 A novel urinary biomarker predicts 1-year mortality after discharge from intensive care Nkuipou-Kenfack, Esther Latosinska, Agnieszka Yang, Wen-Yi Fournier, Marie-Céline Blet, Alice Mujaj, Blerim Thijs, Lutgarde Feliot, Elodie Gayat, Etienne Mischak, Harald Staessen, Jan A. Mebazaa, Alexandre Zhang, Zhen-Yu Crit Care Research 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. BioMed Central 2020-01-09 /pmc/articles/PMC6953276/ /pubmed/31918764 http://dx.doi.org/10.1186/s13054-019-2686-0 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Nkuipou-Kenfack, Esther Latosinska, Agnieszka Yang, Wen-Yi Fournier, Marie-Céline Blet, Alice Mujaj, Blerim Thijs, Lutgarde Feliot, Elodie Gayat, Etienne Mischak, Harald Staessen, Jan A. Mebazaa, Alexandre Zhang, Zhen-Yu A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title | A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title_full | A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title_fullStr | A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title_full_unstemmed | A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title_short | A novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
title_sort | novel urinary biomarker predicts 1-year mortality after discharge from intensive care |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953276/ https://www.ncbi.nlm.nih.gov/pubmed/31918764 http://dx.doi.org/10.1186/s13054-019-2686-0 |
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