Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis

Abstract

Objective: Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls.

Methods: sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure.

Results: There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02-60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3.

Conclusion: Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.

Figure 1

Differences in sRAGE levels between survivors and non-survivors on days 1 and 3. sRAGE, soluble receptor for advanced glycation end products.

Figure 2

Receiver operating characteristics of individual biomarkers for predicting 28-day mortality. Left panel, day 1; right panel, day 3. sRAGE shows superior characteristics to other biomarkers on day 3. sRAGE, soluble receptor for advanced glycation end products; PCT, procalcitonin; CRP, C-reactive protein.

Figure 3

The correlation between soluble receptor for advanced glycation end products (sRAGE) levels and Acute Physiologic and Chronic Health Evaluation (APACHE) II score on days 1 and 3.

Figure 4

Differences in sRAGE levels between patients with vs. without ARDS on days 1 and 3. sRAGE, soluble receptor for advanced glycation end products; ARDS, acute respiratory distress syndrome.

Figure 5

Differences in lactate levels between patients with vs. without ARDS on days 1 and 3. ARDS, acute respiratory distress syndrome.