scholarly journals Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COVID-19 disease severity and indicator of the need for mechanical ventilation, ARDS and mortality

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adeline Lim ◽  
Aleksandar Radujkovic ◽  
Markus A. Weigand ◽  
Uta Merle
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Disease Severity ◽  
Sofa Score ◽  
Oxygen Therapy ◽  
Advanced Glycation Endproducts ◽  
Severe Disease ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Srage Level

Abstract Background COVID-19 pneumonia and subsequent respiratory failure is causing an immense strain on intensive care units globally. Early prediction of severe disease enables clinicians to avoid acute respiratory distress syndrome (ARDS) development and improve management of critically ill patients. The soluble receptor of advanced glycation endproducts (sRAGE) is a biomarker shown to predict ARDS. Although sRAGE level varies depending on the type of disease, there is limited information available on changes in sRAGE levels in COVID-19. Therefore, sRAGE was measured in COVID-19 patients to determine sRAGE level variation in COVID-19 severity and to examine its ability to predict the need for mechanical ventilation (MV) and mortality in COVID-19. Methods In this single-centre observational cohort study in Germany, serum sRAGE during acute COVID-19, 20 weeks after the start of COVID-19 symptoms, as well as in control groups of non-COVID-19 pneumonia patients and healthy controls were measured using ELISA. The primary endpoint was severe disease (high-flow nasal oxygen therapy (HFNO)/MV and need of organ support). The secondary endpoints were respiratory failure with need of MV and 30-day mortality. The area under the curve (AUC), cut-off based on Youden’s index and odds ratio with 95% CI for sRAGE were calculated with regard to prediction of MV need and mortality. Results Serum sRAGE in 164 COVID-19 patients, 101 matched COVID-19 convalescent patients, 23 non-COVID-19 pneumonia patients and 15 healthy volunteers were measured. sRAGE level increased with COVID-19 severity, need for oxygen therapy, HFNO/MV, ARDS severity, need of dialysis and catecholamine support, 30-day mortality, sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) score. sRAGE was found to be a good predictor of MV need in COVID-19 inpatients and mortality with an AUC of 0.871 (0.770–0.973) and 0.903 (0.817–0.990), respectively. When adjusted for male gender, age, comorbidity and SOFA score ≥ 3, sRAGE was independently associated with risk of need for HFNO/MV. When adjusted for SOFA score ≥ 3, sRAGE was independently associated with risk of need for MV. Conclusions Serum sRAGE concentrations are elevated in COVID-19 patients as disease severity increases. sRAGE should be considered as a biomarker for predicting the need for MV and mortality in COVID-19.

scholarly journals Serum uric acid, disease severity and outcomes in COVID-19

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Inès Dufour ◽  
Alexis Werion ◽  
Leila Belkhir ◽  
Anastazja Wisniewska ◽  
Marie Perrot ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Uric Acid ◽  
Respiratory Failure ◽  
Confidence Interval ◽  
Proximal Tubule ◽  
Disease Severity ◽  
Serum Levels ◽  
Kidney Proximal Tubule ◽  
Urate Transporter ◽  
Low Serum

Abstract Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

sRAGE Is Elevated in the Lungs of Premature Infants Receiving Mechanical Ventilation

2017 ◽  
Vol 34 (09) ◽  
pp. 911-917 ◽  
Author(s):  
Jennifer Bradley ◽  
Simon Karam ◽  
Henry Rozycki
Keyword(s):  
Mechanical Ventilation ◽  
Distress Syndrome ◽  
Very Low Birth Weight ◽  
Ventilatory Support ◽  
Soluble Receptor ◽  
Cell Adherence ◽  
Advanced Glycation ◽  
Immunohistochemistry Analysis ◽  
Glycation End Products ◽  
Tracheal Aspirates

Background Soluble receptor for advanced glycation end-products (sRAGE), a soluble isoform of the RAGE receptor, is elevated in lungs from patients with acute conditions such as acute respiratory distress syndrome and bronchiolitis. This study investigated whether sRAGE is present in ventilated infants. Methods Tracheal aspirates from the first week or the fifth week of life were obtained from intubated very low birth weight subjects and analyzed by Western blot. Immunohistochemistry analysis for sRAGE was performed on paraffin-embedded lung autopsy slides from 19 other infants. Results The sRAGE band densities were similar among the seven infants who fully recovered, eight who developed bronchopulmonary dysplasia (BPD), and 5 who died (analysis of variance p = 0.797) but was higher at 4 weeks, p = 0.0324. There was minimal sRAGE staining in the autopsied lungs from previable infants (20–21 weeks) or from those who were not ventilated or had mild lung disease. In contrast, substantial staining was present in two of three with BPD, and those who received high ventilatory support. Conclusion sRAGE is present in ventilated infants. Levels are generally higher in those who receive prolonged or vigorous mechanical ventilation. Since sRAGE may have roles in inflammation and cell adherence, its role in the development of BPD may warrant study.

scholarly journals Racial differences in circulating levels of the soluble receptor for advanced glycation endproducts in middle-aged and older adults

Metabolism ◽  
2017 ◽  
Vol 70 ◽  
pp. 98-106 ◽  
Author(s):  
Tina E. Brinkley ◽  
Xiaoyan Leng ◽  
Barbara J. Nicklas ◽  
Stephen B. Kritchevsky ◽  
Jingzhong Ding ◽  
...  
Keyword(s):  
Older Adults ◽  
Racial Differences ◽  
Advanced Glycation Endproducts ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Middle Aged ◽  
Glycation Endproducts ◽  
Circulating Levels

scholarly journals Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shou-En Wu ◽  
Yi-Lin Chiu ◽  
Tung-Wei Kao ◽  
Wei-Liang Chen
Keyword(s):  
Muscle Mass ◽  
Advanced Glycation End Products ◽  
Community Dwelling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Health Examination ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Srage Level ◽  
Glycation End Products ◽  
End Products

Abstract Background The soluble receptor for advanced glycation end products (sRAGE) has been proposed to serve as a marker for disease severity, but its role in sarcopenia, an age-related progressive loss of muscle mass and function, remains elusive. This study examines the association between sRAGE and sarcopenia. Methods A total of 314 community-dwelling elderly adults who had their health examination at Tri-Service General Hospital from 2017 to 2019 underwent protein analysis with enzyme-linked immunosorbent assay. The relationship with sarcopenia and its detailed information, including components and diagnosis status, were examined using linear and logistic regressions. Results As for sarcopenia components, low muscle mass (β = 162.8, p = 0.012) and strength (β = 181.31, p = 0.011) were significantly correlated with sRAGE, but not low gait speed (p = 0.066). With regard to disease status, confirmed sarcopenia (β = 436.93, p < 0.001), but not probable (p = 0.448) or severe sarcopenia (p = 0.488), was significantly correlated with sRAGE. In addition, females revealed a stronger association with sRAGE level by showing significant correlations with low muscle mass (β = 221.72, p = 0.014) and low muscle strength (β = 208.68, p = 0.043). Conclusions sRAGE level showed a positive association with sarcopenia, illustrating its involvement in the evolution of sarcopenia. This association is more evident in female groups, which may be attributed to the loss of protection from estrogen in postmenopausal women. Utilizing sRAGE level as a prospective marker for sarcopenia deserves further investigation in future studies.

Association between acute respiratory failure requiring mechanical ventilation and the production of advanced glycation end products

2020 ◽  
Vol 68 (7) ◽  
pp. 1235-1240
Author(s):  
Hawa Edriss ◽  
Adebayo J Molehin ◽  
Rocio Gavidia ◽  
Kavitha Selvan ◽  
Kenneth Nugent
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Advanced Glycation End Products ◽  
Glycated Hemoglobin ◽  
Glycated Albumin ◽  
Advanced Glycation ◽  
Control Subjects ◽  
Glycation End Products ◽  
End Products

Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.

scholarly journals Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze

2020 ◽  
Author(s):  
Jason T Patregnani ◽  
Michimasa Fujiogi ◽  
Carlos A Camargo ◽  
Bonnie A Brooks ◽  
Claire E Hoptay ◽  
...  
Keyword(s):  
Intensive Care ◽  
Advanced Glycation End Products ◽  
Mediation Analysis ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Srage Level ◽  
Glycation End Products ◽  
End Products ◽  
Recurrent Wheeze ◽  
Causal Mediation Analysis

Abstract Background Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze. Methods A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze. Results In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30). Conclusions Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.

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