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Am J Physiol Lung Cell Mol Physiol. 2019 Mar 6. doi: 10.1152/ajplung.00359.2018. [Epub ahead of print]

Expression of soluble receptor for advanced glycation end products (sRAGE) is associated with disease severity in congenital diaphragmatic hernia.

Author information

1
Neonatology and Pediatric Critical Care Medicine, University Bonn Children's Hospital, Germany.
2
Department of Obstetrics and Prenatal Medicine, University of Bonn.
3
Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn.

Abstract

Pulmonary hypertension (PH) and lung hypoplasia are major contributors to morbidity and mortality in newborns with congenital diaphragmatic hernia (CDH). The soluble receptor for advanced glycation end products (sRAGE) is a marker of endothelial function and might be associated with disease severity in CDH newborns. In a cohort of 30 CDH newborns and 20 healthy control newborns, sRAGE concentration was measured at birth, at 6 hours, 12 hours, 24 hours, 48 hours, and 7-10 days. In healthy newborns, sRAGE was significantly higher at birth and at 48 hours compared to CDH newborns (both p<0.001). Among CDH newborns, sRAGE was significantly lower at birth (p=0.033) and at 7-10 days (p=0.035) in patients receiving extracorporeal membrane oxygenation (ECMO) compared to patients not receiving ECMO. In contrast, CDH newborns receiving ECMO had significantly higher values at 6 hours (p=0.001), 12 hours (p=0.004), and 48 hours (0.032). Additionally, sRAGE correlated significantly with PH severity, intensity and duration of mechanical ventilation and prenatally assessed markers of CDH severity (lung size, liver herniation). The probability to receive ECMO therapy was five times higher in CDH newborns with sRAGE concentrations below the calculated cutoff of 650 pg/ml at birth (p=0.002) and nine times higher in CDH newborns with sRAGE concentrations above the cutoff of 3500 pg/ml at 6 hours (p=0.001). These findings suggest a potential involvement of sRAGE in the pathophysiology of CDH and may act as a therapeutic target in future treatment approaches.

KEYWORDS:

Congenital diaphragmatic hernia; extracorporeal membrane oxygenation; pulmonary hypertension; receptor for advanced glycation end products; sRAGE

PMID:
30838867
DOI:
10.1152/ajplung.00359.2018

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