Associations of Plasma Angiopoietins-1 and -2 and Angiopoietin-2/-1 Ratios With Measures of Organ Injury and Clinical Outcomes in Children With Sepsis: A Preliminary Report.


Journal

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
ISSN: 1529-7535
Titre abrégé: Pediatr Crit Care Med
Pays: United States
ID NLM: 100954653

Informations de publication

Date de publication:
09 2020
Historique:
pubmed: 3 8 2020
medline: 7 1 2021
entrez: 3 8 2020
Statut: ppublish

Résumé

Results from preclinical and adult sepsis studies suggest that the balance of circulating angiopoietin-1 and -2 levels, represented as angiopoietin-2/-1 ratios, plays a pivotal role in mediating vascular dysfunction and organ injury during sepsis. However, the relationship of plasma angiopoietins with organ injury and clinical outcomes in children with sepsis remains unknown. We sought to determine whether plasma angiopoietin-1 and -2 levels and angiopoietin-2/-1 ratios in the acute phase of sepsis correlated with measures of organ injury and clinical outcomes in children with sepsis. Prospective observational cohort study. PICU within a tertiary freestanding children's hospital. Children 18 years old or less and greater than 3 kg admitted to the PICU for sepsis. None. Plasma angiopoietin-1 and -2 levels were measured in 38 children with sepsis 0-6, 24, 48, and 72 hours following PICU admission. Children with elevated pediatric Sequential Organ Failure Assessment scores on the third day after PICU admission demonstrated significantly higher 24-72-hour angiopoietin-2/-1 ratios predominantly as a function of higher angiopoietin-2 levels. In children with sepsis-induced organ dysfunction, angiopoietin-2/-1 ratios correlated with oxygenation indices and serum levels of creatinine and bilirubin. Forty-eight- and 72-hour angiopoietin-2/-1 ratios correlated with PICU length of stay (Spearman rho = 0.485, p = 0.004 and rho = 0.440, p = 0.015, respectively). In the acute phase of sepsis in children, plasma angiopoietin-2/-1 ratios rise significantly above control levels and correlate with measures of organ injury and worse clinical outcomes after 24 hours. Our findings suggest that angiopoietin dysregulation begins early in sepsis and, if sustained, may promote greater organ injury that can lead to worse clinical outcomes.

Identifiants

pubmed: 32740186
doi: 10.1097/PCC.0000000000002508
pii: 00130478-202009000-00059
doi:

Substances chimiques

Angiopoietin-1 0
Angiopoietin-2 0

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e874-e878

Références

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810
Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003; 101:3765–3777
London NR, Whitehead KJ, Li DY. Endogenous endothelial cell signaling systems maintain vascular stability. Angiogenesis 2009; 12:149–158
Sundberg C, Kowanetz M, Brown LF, et al. Stable expression of angiopoietin-1 and other markers by cultured pericytes: Phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest 2002; 82:387–401
Abou-Khalil R, Le Grand F, Pallafacchina G, et al. Autocrine and paracrine angiopoietin 1/Tie-2 signaling promotes muscle satellite cell self-renewal. Cell Stem Cell 2009; 5:298–309
Richter RP, Russell RT, Hu PJ, et al. Plasma angiopoietin-2/-1 ratio is elevated and angiopoietin-2 levels correlate with plasma syndecan-1 following pediatric trauma. Shock 2019; 52:340–346
Giuliano JS Jr, Tran K, Li FY, et al. The temporal kinetics of circulating angiopoietin levels in children with sepsis. Pediatr Crit Care Med 2014; 15:e1–e8
Ricciuto DR, dos Santos CC, Hawkes M, et al. Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med 2011; 39:702–710
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis: International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2–8
Aghai ZH, Faqiri S, Saslow JG, et al. Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: Attenuation by dexamethasone. J Perinatol 2008; 28:149–155
Carcillo JA, Podd B, Aneja R, et al. Pathophysiology of pediatric multiple organ dysfunction syndrome. Pediatr Crit Care Med 2017; 18:S32–S45
Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically ill children. JAMA Pediatr 2017; 171:e172352
Giuliano JS Jr, Lahni PM, Harmon K, et al. Admission angiopoietin levels in children with septic shock. Shock 2007; 28:650–654
Siner JM, Bhandari V, Engle KM, et al. Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock 2009; 31:348–353
Wong HR, Cvijanovich N, Lin R, et al. Identification of pediatric septic shock subclasses based on genome-wide expression profiling. BMC Med 2009; 7:34
Raymond SL, López MC, Baker HV, et al. Unique transcriptomic response to sepsis is observed among patients of different age groups. PLoS One 2017; 12:e0184159
Parikh SM, Mammoto T, Schultz A, et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med 2006; 3:e46
Davis B, Dei Cas A, Long DA, et al. Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 2007; 18:2320–2329
Davis JS, Yeo TW, Piera KA, et al. Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity. Crit Care 2010; 14:R89
Lee SJ, Lee CK, Kang S, et al. Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. J Clin Invest 2018; 128:5018–5033
Dallabrida SM, Ismail N, Oberle JR, et al. Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins. Circ Res 2005; 96:e8–e24
Melendez E, Whitney JE, Norton JS, et al. Systemic angiopoietin-1/2 dysregulation in pediatric sepsis and septic shock. Int J Med Sci 2019; 16:318–323
Carcillo JA, Halstead ES, Hall MW, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network Investigators: Three hypothetical inflammation pathobiology phenotypes and pediatric sepsis-induced multiple organ failure outcome. Pediatr Crit Care Med 2017; 18:513–523
Zonneveld R, Jongman R, Juliana A, et al. Low serum angiopoietin-1, high serum angiopoietin-2, and high Ang-2/Ang-1 protein ratio are associated with early onset sepsis in Surinamese newborns. Shock 2017; 48:638–643
Pierce RW, Shabanova V, Canarie M, et al. Angiopoietin level trajectories in toddlers with severe sepsis and septic shock and their effect on capillary endothelium. Shock 2019; 51:298–305

Auteurs

Robert P Richter (RP)

Division of Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.

Lei Zheng (L)

Division of Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
Division of Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.

Amit R Ashtekar (AR)

Division of Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
Division of Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.

Shannon C Walker (SC)

University of Alabama at Birmingham School of Medicine, Birmingham, AL.

Jean-Francois Pittet (JF)

Division of Critical Care Anesthesiology, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL.

Jillian R Richter (JR)

Division of Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH