Study on the value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 and growth differentiation factor-15 in the diagnosis of sepsis: test results from the patients of a multicenter study / 中华危重病急救医学

ABSTRACT

Objective:To investigate the diagnostic value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 (FAHD1) and growth differentiation factor-15 (GDF-15) in sepsis.Methods:Based on the database of the whole process of sepsis early warning, diagnosis and treatment management, which was established on the study of sepsis early warning and standardized diagnosis and treatment system, adult patients with suspected infection admitted to the department of critical care medicine of Zhejiang Hospital, Second Affiliated Hospital of Zhejiang University, the First Affiliated Hospital of Sun Yat-Sen University, West China Hospital of Sichuan University, Ningbo First Hospital from May 2014 to October 2015 were enrolled. The basic vital signs, and the main blood routine results, liver and kidney function, blood gas, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) score at the time of diagnosis of patients with or without sepsis were analyzed. The preserved serum samples were taken, the levels of procalcitonin (PCT), C-reactive protein (CRP) were detected by electrochemiluminescence method, immunoturbidimetry respectively, and FAHD1 and GDF-15 were detected by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression were used to analyze the risk factors for sepsis diagnose. The indexes' diagnostic efficacy in sepsis were analyzed by receiver operating characteristics curve (ROC curve).Results:A total of 132 patients were enrolled, including 76 cases of sepsis and 56 cases of non-sepsis. Compared with the non-sepsis group, the heart rate in the sepsis group was increased (bpm 116.4±17.8 vs. 97.4±19.1), while the mean arterial pressure (MAP), platelet count (PLT), arterial partial pressure of oxygen (PaO 2) were significantly decreased [MAP (mmHg, 1 mmHg = 0.133 kPa) 65.8±9.7 vs. 74.7±10.3, PLT (×10 9/L) 120 (69, 204) vs. 163 (117, 239), PaO 2 (mmHg) 83.0 (66.6, 108.0) vs. 108.0 (84.4, 130.0), all P < 0.05], direct bilirubin (DBil), serum creatinine (SCr), lactic acid (Lac), APACHEⅡ score and SOFA score were significantly increased [DBil (μmol/L) 13.00 (5.55, 55.31) vs. 6.20 (2.20, 21.90), SCr (μmol/L) 118.00 (70.00, 191.73) vs. 77.20 (59.65, 110.86), Lac (mmol/L) 2.90 (1.50, 4.10) vs. 1.90 (1.20, 2.80), APACHEⅡ score 20.0 (16.0, 25.0) vs. 16.0 (10.0, 21.0), SOFA score 12.0 (8.0, 16.0) vs. 8.0 (5.0, 13.0), all P < 0.05]. In addition, the serum levels of FAHD1, GDF-15, PCT and CRP in sepsis group were significantly higher than those in non-sepsis group [FAHD1 (μg/L) 3.96 (2.25, 5.92) vs. 2.47 (1.03, 3.54), GDF-15 (μg/L) 8.46 (4.37, 19.68) vs. 4.32 (1.74, 10.39), PCT (μg/L) 3.79 (1.37, 11.32) vs. 0.42 (0.12, 2.14), CRP (mg/L) 154.43 (61.33, 283.20) vs. 65.95 (28.15, 144.69), all P < 0.01]. Multivariate Logistic regression showed that serum FAHD1 [odds ratio ( OR) = 1.135, 95% confidence interval (95% CI) was 1.045-1.234], GDF-15 ( OR = 1.090, 95% CI was 1.029-1.155) and CRP ( OR = 1.007, 95% CI was 1.002-1.011) were risk factors for sepsis (all P < 0.05). ROC curve analysis of sepsis showed that the areas under ROC curve (AUC) of serum mitochondrial associated proteins FAHD1 and GDF-15 were 0.727 (95% CI was 0.641-0.802) and 0.677 (95% CI was 0.588-0.757), respectively; and the AUC of classical infection indexes PCT and CRP were 0.767 (95% CI was 0.683-0.837) and 0.680 (95% CI was 0.59-0.760), respectively. There was no significant difference between the AUC of mitochondrial associated proteins and classical infection indexes. The combination of FAHD1, GDF-15, PCT and CRP had the largest AUC, which was 0.809 (95% CI was 0.730-0.874), and the sensitivity was 75.00%, and the specificity was 80.00%. Conclusion:Mitochondrial associated protein FAHD1 and GDF-15 are associated with sepsis, and the diagnostic efficiency is improved when combined with PCT and CRP, which might provide experimental basis for screening diagnostic markers of sepsis.