Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study

Long-xiang Su, Lin Feng, Jie Zhang, Yong-jiu Xiao, Yan-hong Jia, Peng Yan, Dan Feng, Li-xin Xie, Long-xiang Su, Lin Feng, Jie Zhang, Yong-jiu Xiao, Yan-hong Jia, Peng Yan, Dan Feng, Li-xin Xie

Abstract

Introduction: We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN).

Methods: We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made.

Results: On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence.

Conclusions: Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients.

Trial registration: ClinicalTrial.gov identifier NCT01333657.

Figures

Figure 1
Figure 1
ROC curves for urine sTREM-1 and APACHEII for distinguishing sepsis from SIRS. Area under the curve (AUC) turned out respectively as urine sTREM-1 0.797 (95% CI 0.711 to 0.884) and APACHE II score 0.722 (95% CI 0.586 to 0.858). Using a cut-off point for urine sTREM-1 of 34.2 pg/ml, the sensitivity was 0.643, the specificity was 0.938, Positive Predictive Value (PPV) was 0.983, Negative Predictive Value (NPV) was 0.198 and Youden index (YI) was 0.581. Using a cut-off point for APACHE II score of 13.5, the sensitivity was 0.714, the specificity was 0.625, PPV was 0.913, NPV was 0.197 and YI was 0.339. ROC curves, Receiver Operating Characteristic curves;sTREM-1, soluble triggering receptor expressed on myeloid cells-1; APACHEII, acute physiologic assessment and chronic health evaluationII;SIRS, systemic inflammatory response syndrome.
Figure 2
Figure 2
sTREM-1 (A), WBC (B), CRP (C), and PCT (D) levels measured over 14 days at different stages of sepsis..*P < 0.05, **P < 0.01, ***P < 0.001. CRP, C-reactive protein; PCT, procalcitonin; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; WBC, White blood cells.
Figure 3
Figure 3
sTREM-1 (A), WBC (B), CRP (C), and PCT (D) levels measured over 14 days based on 28-day survival. The differences of patients diagnosed with sepsis in urine sTREM-1 and serum PCT levels at these six different time points were statistically significant (P < 0.05), with the non-survivors group having higher values at all time points, and also showing a higher CRP level on days 7, 10 and 14, which were also statistically significant (P < 0.05). WBC counts in the non-survivors group were also higher than that of the survivors group, but with no apparent difference between them at all time points. CRP, C-reactive protein; PCT, procalcitonin; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; WBC, white blood cells.
Figure 4
Figure 4
ROC curves for urine sTREM-1, SCr, BUN level for diagnosing AKI before 48 hours. ROC curves, Receiver Operating Characteristic curves;sTREM-1, soluble triggering receptor expressed on myeloid cells-1; SCR, serum creatinine; BUN, blood urea nitrogen; AKI, acute kidney injury.

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