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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 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.

SUBMITTER: Nkuipou-Kenfack E

PROVIDER: S-EPMC6953276 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Nkuipou-Kenfack Esther E Latosinska Agnieszka A Yang Wen-Yi WY Fournier Marie-Céline MC Blet Alice A Mujaj Blerim B Thijs Lutgarde L Feliot Elodie E Gayat Etienne E Mischak Harald H Staessen Jan A JA Mebazaa Alexandre A Zhang Zhen-Yu ZY

Critical care (London, England) 20200109 1

<h4>Rationale</h4>The urinary proteome reflects molecular drivers of disease.<h4>Objectives</h4>To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.<h4>Methods</h4>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 classi ...[more]

PMID: 31918764

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Project description:RationaleSurvivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level.ObjectivesTo identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use.MethodsMatched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses.Measurements and main resultsOf 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity.ConclusionsThis complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society.

Project description:PurposeThe final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge.MethodsPatients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors).ResultsNon-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771-0.890) for PCT, 0.688 (0.566-0.810) for albumin, 0.861 (0.796-0.927) for SOFA score, and increased to 0.913 (0.858-0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis.ConclusionsSerum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction.

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

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

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