10 research outputs found

    Additional file 1: of Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients

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    Pairwise correlation matrix of endothelial and inflammatory biomarkers. Pearson’s correlation coefficient (ρ) was used to estimate the magnitude of the linear correlation between log-transformed biomarker concentrations. (DOCX 15 kb

    Additional file 2: of Association of markers of endothelial dysregulation Ang1 and Ang2 with acute kidney injury in critically ill patients

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    Associations of biomarkers with AKI (Stage 2–3 versus no AKI). For associations of biomarkers with the risk of AKI, we examined associations of biomarkers with severe AKI, to increase specificity of the outcome definition. (DOCX 15 kb

    Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness

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    <div><p>Background</p><p>Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS.</p><p>Methods</p><p>We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers.</p><p>Results</p><p>Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes.</p><p>Conclusions</p><p>In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.</p></div

    Subject Characteristics.

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    <p>SD = Standard Deviation; APACHE III = Acute Physiology and Chronic Health Evaluation III; BMI = Body Mass Index</p><p>Subject Characteristics.</p

    Multivariate Analysis of Biomarker Association with Shock.

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    <p>OR = Odds Ratio per doubling; CI = Confidence Interval; APACHE III = Acute Physiology and Chronic Health Evaluation III.</p><p><sup><i>a</i></sup> Logistic regression adjusted for age, gender, presence of infection, admitting service (medical vs. surgical), source of admission (outside hospital vs. emergency room), body mass index, smoking status, diabetes mellitus, chronic renal insufficiency, and cirrhosis</p><p><sup><i>b</i></sup> Adjusted for Log<sub>2</sub>(IL-6) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t004fn002" target="_blank"><sup>a</sup></a>.</p><p><sup><i>c</i></sup> Adjusted for Log<sub>2</sub>(sTNFR-1) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t004fn003" target="_blank"><sup>b</sup></a>.</p><p><sup><i>d</i></sup> For the number of tests in this table, a Bonferroni p<0.05 is equivalent to p<2.08x10<sup>-3</sup></p><p>Multivariate Analysis of Biomarker Association with Shock.</p

    Multivariate Analysis of Biomarker Association with 28 Day Mortality.

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    <p>OR = Odds Ratio per doubling; CI = Confidence Interval; APACHE III = Acute Physiology and Chronic Health Evaluation III.</p><p><sup><i>a</i></sup> Logistic regression adjusted for age, gender, presence of infection, admitting service (medical vs. surgical), source of admission (outside hospital vs. emergency room), body mass index, smoking status, diabetes mellitus, chronic renal insufficiency, and cirrhosis</p><p><sup><i>b</i></sup> Adjusted for APACHE III and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t003fn002" target="_blank"><sup>a</sup></a>.</p><p><sup><i>c</i></sup> Adjusted for Log<sub>2</sub>(IL-6) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t003fn002" target="_blank"><sup>a</sup></a>.</p><p><sup><i>d</i></sup> Adjusted for Log<sub>2</sub>(sTNFR-1) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t003fn002" target="_blank"><sup>a</sup></a>.</p><p><sup>e</sup> For the number of tests in this table, a Bonferroni p<0.05 is equivalent to p<1.56x10<sup>-3</sup></p><p>Multivariate Analysis of Biomarker Association with 28 Day Mortality.</p

    Multivariate Analysis of Biomarker Association with Day 3 SOFA Score.

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    <p>SOFA = sequential organ failure assessment, β = Beta coefficient for increase in SOFA score with each doubling of biomarker concentration; CI = confidence interval.</p><p><sup><i>a</i></sup> Linear regression adjusted for age, gender, presence of infection, admitting service (medical vs. surgical), source of admission (outside hospital vs. emergency room), body mass index, smoking status, diabetes mellitus, chronic renal insufficiency, and cirrhosis</p><p><sup><i>b</i></sup> Adjusted for Log<sub>2</sub>(IL-6) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t005fn002" target="_blank"><sup>a</sup></a>.</p><p><sup><i>c</i></sup> Adjusted for Log<sub>2</sub>(sTNFR-1) concentration and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141251#t005fn002" target="_blank"><sup>a</sup></a>.</p><p><sup>e</sup> For the number of tests in this table, a Bonferroni p<0.05 is equivalent to p<1.56x10<sup>-3</sup></p><p>Multivariate Analysis of Biomarker Association with Day 3 SOFA Score.</p

    Comparison of Plasma Biomarkers and 28 day mortality.

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    <p>IQR = Interquartile Range; IL-6 = Interleukin-6; IL-8 = Interleukin-8; G-CSF = Granulocyte colony stimulating factor; sTNFR-1 = Soluble Tumor Necrosis Factor Receptor-1; Ang-1 = Angiopoietin-1; Ang-2 = Angiopoietin-2; sVCAM-1 = Soluble Vascular Adhesion Molecule-1.</p><p><sup><i>a</i></sup> P value for Mann-Whitney U Test</p><p>Comparison of Plasma Biomarkers and 28 day mortality.</p

    Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis

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    Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR).The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses.Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]).In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations. Importance Objective Design, setting, and participants Exposures Main outcomes and measures Results Conclusions and relevance</h4

    Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

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    OBJECTIVE:To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN:Individual participant data meta-analysis. SETTING:Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS:Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES:GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS:Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS:Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR
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