A novel urinary biomarker predicts 1-year mortality after discharge from intensive care
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 s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Critical Care |
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| Online Access: | https://doi.org/10.1186/s13054-019-2686-0 |
| _version_ | 1818970876804071424 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Esther Nkuipou-Kenfack |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T14:43:27Z |
| format | Article |
| id | doaj.art-75856f679f5c40cd8d8c09326b1f1831 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-12-20T14:43:27Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-75856f679f5c40cd8d8c09326b1f18312022-12-21T19:37:11ZengBMCCritical Care1364-85352020-01-0124111110.1186/s13054-019-2686-0A novel urinary biomarker predicts 1-year mortality after discharge from intensive careEsther Nkuipou-Kenfack0Agnieszka Latosinska1Wen-Yi Yang2Marie-Céline Fournier3Alice Blet4Blerim Mujaj5Lutgarde Thijs6Elodie Feliot7Etienne Gayat8Harald Mischak9Jan A. Staessen10Alexandre Mebazaa11Zhen-Yu Zhang12The French and European Outcome Registry in Intensive Care Unit InvestigatorsMosaiques Diagnostics GmbHMosaiques Diagnostics GmbHStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of LeuvenDepartment of Anesthesiology and Intensive Care, Saint Louis-Lariboisière – Fernand Widal University Hospital, Assistance Publique Hôpitaux de ParisDepartment of Anesthesiology and Intensive Care, Saint Louis-Lariboisière – Fernand Widal University Hospital, Assistance Publique Hôpitaux de ParisStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of LeuvenStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of LeuvenDepartment of Anesthesiology and Intensive Care, Saint Louis-Lariboisière – Fernand Widal University Hospital, Assistance Publique Hôpitaux de ParisDepartment of Anesthesiology and Intensive Care, Saint Louis-Lariboisière – Fernand Widal University Hospital, Assistance Publique Hôpitaux de ParisMosaiques Diagnostics GmbHStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of LeuvenDepartment of Anesthesiology and Intensive Care, Saint Louis-Lariboisière – Fernand Widal University Hospital, Assistance Publique Hôpitaux de ParisStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of LeuvenAbstract 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.https://doi.org/10.1186/s13054-019-2686-0BiomarkerIntensive care medicineHeart failureMortalityUrinary proteomics |
| spellingShingle | 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 A novel urinary biomarker predicts 1-year mortality after discharge from intensive care Critical Care Biomarker Intensive care medicine Heart failure Mortality Urinary proteomics |
| 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 | Biomarker Intensive care medicine Heart failure Mortality Urinary proteomics |
| url | https://doi.org/10.1186/s13054-019-2686-0 |
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