Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

Abstract

BackgroundCommunity-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome.MethodWe evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission.ResultsThirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome.ConclusionThe association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.

Limited Role of the Receptor for Advanced Glycation End Products during <b><i>Streptococcus pneumoniae</i></b> Bacteremia

“…sRAGE levels are elevated and suggested to be a marker of outcome in patients with sepsis [29], pneumonia [30] and acute lung injury [31]. In this study, we were unable to detect sRAGE in plasma, which is in accordance with an earlier study measuring circulating sRAGE levels in diabetic mice [32].…”

Biomarkers in acute respiratory distress syndrome

“…Its utility as a marker of ARDS in humans, however, is questionable and data have been very mixed. Some studies have shown an association between plasma sRAGE levels and ARDS development in mixed ICU patients [17, 36,86] and trauma patients [87], but several robust studies have not shown any association [7 & , 10,11] and it is likely that sRAGE is a marker of illness severity rather than ARDS.…”

Soluble RAGEs — Prospects for treating & tracking metabolic and inflammatory disease

“…For example, it is possible that in general, endothelial cells are the major producers of soluble RAGEs but that in diabetes, peripheral blood monocytes and lymphocytes may also contribute substantially to soluble RAGE production. In this context, in subjects with sepsis, a dramatic form of disease manifestation with heightened inflammatory linked to hemodynamic abnormalities, sRAGE levels in plasma were found to be significantly higher than in control subjects [44]. Hence, we might speculate, is diabetes somewhere in the middle?…”