Serum Soluble Endoglin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome.

Abstract Background: Multiple organ dysfunction syndrome (MODS) is the final common pathway in critical illness and is associated with significant morbidity and mortality. Endothelial activation is a key driver of organ dysfunction. Soluble endoglin (sENG) is highly expressed by mature and progenitor endothelial cells and considered to have angiogenic properties. We sought to determine the association between sENG and pediatric septic shock outcomes, differences across risk strata reflective of systemic inflammation, and correlation with established markers of endothelial dysfunction. Methods: Prospective observational study of pediatric septic shock. Endothelial biomarkers including sENG were measured using multiplex Luminex assays among patients with existing data on pediatric sepsis biomarker risk model data (PERSEVERE-II). Primary outcome of interest was complicated course a composite of death by (or) MODS on day 7 of illness. Secondary outcomes were 6 individual organ dysfunctions. Multivariable regression was used to test the independent association between sENG and outcomes of interest. We compared sENG concentrations across PERSEVERE-II mortality risk strata and correlations with established markers of endothelial dysfunction. Results: 306 patients of whom 100 patients had complicated course. Serum ENG concentrations were higher among those with primary and secondary outcomes of interest, with the exception of acute neurological dysfunction. sENG was independently associated with increased odds of complicated course [adj OR 1.53 (95% CI: 1.02-2.27), p=0.038] and acute renal dysfunction [adj OR 1.84 (95%CI: 1.18-2.876), p=0.006]. sENG demonstrated graded responses across PERSEVERE-II risk strata and was positively correlated with endothelial biomarkers, except Angiopoietin-1. Conclusions: Soluble endoglin is independently associated with death and persistent MODS and acute renal dysfunction in pediatric septic shock. Future studies are required to validate our observational data and mechanistic studies are necessary to elucidate the role of ENG in critical illness pathobiology.