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

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.

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Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after Pneumonectomy

Anesthesiology ◽

10.1097/00000542-200607000-00007 ◽

2006 ◽

Vol 105 (1) ◽

pp. 14-18 ◽

Cited By ~ 196

Author(s):

Evans R. Fernández-Pérez ◽

Mark T. Keegan ◽

Daniel R. Brown ◽

Rolf D. Hubmayr ◽

Ognjen Gajic

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Confidence Interval ◽

Odds Ratio ◽

Pulmonary Function Tests ◽

Bronchopleural Fistula ◽

Fluid Administration ◽

Postoperative Respiratory Failure ◽

Increased Risk ◽

Duration Of Surgery

Background Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. Methods Patients undergoing elective pneumonectomy at the authors' institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. Results Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12-2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05-1.97). Conclusion Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.

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Sodium-Hydrogen Exchanger Regulatory Factor-1 Interacts with Mouse Urate Transporter 1 to Regulate Renal Proximal Tubule Uric Acid Transport

Journal of the American Society of Nephrology ◽

10.1681/asn.2006090980 ◽

2007 ◽

Vol 18 (5) ◽

pp. 1419-1425 ◽

Cited By ~ 21

Author(s):

Rochelle Cunningham ◽

Marc Brazie ◽

Srilatha Kanumuru ◽

Xiaofei E ◽

Rajat Biswas ◽

...

Keyword(s):

Uric Acid ◽

Proximal Tubule ◽

Renal Proximal Tubule ◽

Acid Transport ◽

Regulatory Factor ◽

Urate Transporter ◽

Sodium Hydrogen ◽

Sodium Hydrogen Exchanger

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Low serum levels of uric acid and albumin in patients with GuillainBarre syndrome

Medicine ◽

10.1097/md.0000000000007318 ◽

2017 ◽

Vol 96 (25) ◽

pp. e7318

Keyword(s):

Uric Acid ◽

Serum Levels ◽

Low Serum

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Vasoactive Intestinal Peptide in Early Spondyloarthritis: Low Serum Levels as a Potential Biomarker for Disease Severity

Journal of Molecular Neuroscience ◽

10.1007/s12031-015-0517-6 ◽

2015 ◽

Vol 56 (3) ◽

pp. 577-584 ◽

Cited By ~ 10

Author(s):

Iria V. Seoane ◽

Eva Tomero ◽

Carmen Martínez ◽

Rosario Garcia-Vicuña ◽

Yasmina Juarranz ◽

...

Keyword(s):

Vasoactive Intestinal Peptide ◽

Disease Severity ◽

Serum Levels ◽

Potential Biomarker ◽

Low Serum

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Low serum levels of uric acid and albumin in patients with Guillain–Barre syndrome

Medicine ◽

10.1097/md.0000000000006618 ◽

2017 ◽

Vol 96 (15) ◽

pp. e6618 ◽

Cited By ~ 11

Author(s):

Zhongqian Su ◽

Zhibo Chen ◽

Yian Xiang ◽

Bingjie Wang ◽

Yuanyuan Huang ◽

...

Keyword(s):

Uric Acid ◽

Serum Levels ◽

Guillain Barre Syndrome ◽

Guillain Barré Syndrome ◽

Guillain Barré ◽

Low Serum

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Low Serum Levels of Uric Acid are Associated With Development of Poststroke Depression

Medicine ◽

10.1097/md.0000000000001897 ◽

2015 ◽

Vol 94 (45) ◽

pp. e1897 ◽

Cited By ~ 9

Author(s):

Yingying Gu ◽

Bin Han ◽

Liping Wang ◽

Yaling Chang ◽

Lin Zhu ◽

...

Keyword(s):

Uric Acid ◽

Serum Levels ◽

Poststroke Depression ◽

Low Serum

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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

Annals of Intensive Care ◽

10.1186/s13613-021-00836-2 ◽

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.

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Hyperuricaemia as a predictor of hospital outcome in patients with sepsis: results of a prospective study

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-021-00079-4 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Mir Nadeem ◽

Bilal Ahmad Mir ◽

Mir Waseem ◽

Tabinda Ayub Shah ◽

Rameez Raja

Keyword(s):

Emergency Department ◽

Mechanical Ventilation ◽

Acute Kidney Injury ◽

Uric Acid ◽

Respiratory Failure ◽

Serum Uric Acid ◽

Kidney Injury ◽

Study Cohort ◽

Early Management ◽

Hospital Outcome

Abstract Background Early management of sepsis in the emergency department improves patient outcomes. The identification of at-risk patients for aggressive management by an easily available biomarker could go a long way in the triage of patients in the emergency department. It is postulated that during sepsis, the majority of patients undergo ischaemic reperfusion injury or inflammation, and uric acid with its oxidant and antioxidant properties may be playing some role and, hence, the measurement of uric acid could possibly predict the hospital course in patients with sepsis. We were prompted to undertake this study as serum uric acid estimation is readily available and economical compared to newly evolving biomarkers in sepsis. Estimation of serum uric acid levels on arrival to the emergency department may prove a useful predictor of hospital outcome in patients with sepsis especially in regions with limited resources. Results Of 102 patients, 55 (53.9%) were males. The mean age of the study cohort was 63.2 ± 10.48. Patients with higher qSOFA scores had higher uric acid levels on admission. While 12 (11.8%) patients had a septicaemic shock, acute kidney injury was recorded in 48 (47.1%) patients and 11 (10.8%) patients required dialysis. Thirty-four (33.3%) patients had respiratory failure, and of these, 21 (20.6%) patients required mechanical ventilation. The overall median stay in the medical intensive care (MICU) was 3days (range 2–7 days). The patients with higher uric acid levels had higher rates of respiratory failure but did not reach significant levels. In 15 (14.7%) patients, 7 males expired (mortality rate of 14.7%). There was a significant association between SOFA score and mortality. Patients who succumbed to sepsis had higher serum uric acid levels on arrival. Conclusions Patients with higher qSOFA scores had higher uric acid levels on admission. Hyperuricaemia predicted acute kidney injury, a requirement of mechanical ventilation and mean hospital stay in patients with sepsis. Further studies may be required to confirm the association.

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