A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2

Abstract

Objective: Sepsis is a leading cause of maternal death, and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis in pregnancy is a risk factor for obstetrical and medical complications, and it is a major cause of sepsis, as bacteremia complicates 15-20% of pyelonephritis episodes in pregnancy. The diagnosis of bacteremia currently relies on blood cultures, whereas a rapid test could allow timely management and improved outcomes. Soluble suppression of tumorigenicity 2 (sST2) was previously proposed as a biomarker for sepsis in non-pregnant adults and children. This study was designed to determine whether maternal plasma concentrations of sST2 in pregnant patients with pyelonephritis can help to identify those at risk for bacteremia.Study design: This cross-sectional study included women with normal pregnancy (n = 131) and pregnant women with acute pyelonephritis (n = 36). Acute pyelonephritis was diagnosed based on a combination of clinical findings and a positive urine culture. Patients were further classified according to the results of blood cultures into those with and without bacteremia. Plasma concentrations of sST2 were determined by a sensitive immunoassay. Non-parametric statistics were used for analysis.Results: The maternal plasma sST2 concentration increased with gestational age in normal pregnancies. Pregnant patients with acute pyelonephritis had a higher median (interquartile range) plasma sST2 concentration than those with a normal pregnancy [85 (47-239) ng/mL vs. 31 (14-52) ng/mL, p < .001]. Among patients with pyelonephritis, those with a positive blood culture had a median plasma concentration of sST2 higher than that of patients with a negative blood culture [258 (IQR: 75-305) ng/mL vs. 83 (IQR: 46-153) ng/mL; p = .03]. An elevated plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% (area under the receiver operating characteristic curve, 0.74; p = .003) with a positive likelihood ratio of 13.8 and a negative likelihood ratio of 0.3 for the identification of patients who had a positive blood culture.Conclusion: sST2 is a candidate biomarker to identify bacteremia in pregnant women with pyelonephritis. Rapid identification of these patients may optimize patient care.

Keywords: Cytokines; IL-1; IL-33; pregnancy; sepsis; septic shock; urinary tract infection.

Figure 1:. Scatterplot demonstrates increased sST2 concentrations among patients with acute pyelonephritis compared to patients with a normal pregnancy.

The X axis shows gestational age (weeks), and the Y axis shows maternal plasma sST2 concentration (ng/mL). A) In normal pregnancy, median maternal plasma sST2 concentrations increased with gestational age (Spearman’s Rho 0.8, p < 0.001). B) Pregnancies complicated by pyelonephritis with negative blood culture alone (blue squares) are plotted against those with positive blood culture (red triangles).

Figure 2:. Plasma sST2 concentrations in normal pregnancy compared to pregnancy complicated by acute pyelonephritis.

In pregnancies complicated by acute pyelonephritis, the median plasma sST2 concentration was significantly higher than that in normal pregnancies [median 85 ng/mL (IQR 47–239) vs. median 31 ng/mL (IQR 14–52); p<0.001].

Figure 3:. Plasma sST2 concentration in normal pregnancy compared to pregnancies complicated by acute pyelonephritis with positive blood culture.

The median plasma sST2 concentration was significantly higher in those with positive blood culture than in those with negative blood culture [median 258 ng/mL (IQR 75-305) vs. median 83 ng/mL (IQR 46–153); p=0.03].

Figure 4:. Receiver Operating Characteristic (ROC) curve demonstrates an area under the curve (AUC) of 0.74 (95% confidence interval 0.50–0.97).

A maternal plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% for identification of patients with a positive blood culture.