Acute pyelonephritis in pregnancy and plasma syndecan-1: evidence of glycocalyx involvement
Creators: name: Immonen, Timothy
name: Jung, Eunjung
name: Gallo, Dahiana M.
name: Diaz-Primera, Ramiro
name: Gotsch, Francesca
name: Whittaker, Peter
name: Than, Nandor Gabor
name: Bosco, Mariachiara
name: Tarca, Adi L.
name: Suksai, Manaphat
name: Romero, Roberto
name: Chaiworapongsa, Tinnakorn
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Molecular Biology
subject: Physiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: Acute pyelonephritis, a risk factor for maternal sepsis, adult respiratory distress syndrome, and preterm labor, is a frequent cause of hospitalization. This condition is characterized by excessive intravascular inflammation and endothelial cell activation and dysfunction. Syndecan-1, a major component of the glycocalyx, is a gel-like layer that covers the luminal surface of healthy endothelial cells, preserving and mediating many endothelial functions. During pregnancy, there is an additional potential source of syndecan-1, the “syncytiotrophoblast glycocalyx,” which lines the intervillous space. Insults that damage the glycocalyx lead to a shedding of syndecan-1 into the circulation. Hence, syndecan-1 has been proposed as a marker of endothelial injury in conditions such as sepsis, trauma, cardiovascular disease, and diabetes mellitus. The objective of this study was to determine whether the plasma syndecan-1 concentration changes in women with acute pyelonephritis in the presence or absence of bacteremia. This cross-sectional study included three groups: (1) non-pregnant women (<i>n</i> = 25); (2) women with an uncomplicated pregnancy from whom samples were collected preterm (<i>n</i> = 61) or at term (<i>n</i> = 69); and (3) pregnant women diagnosed with acute pyelonephritis from whom samples were collected at the time of diagnosis during the second and third trimesters (<i>n</i> = 33). The diagnosis of acute pyelonephritis was based on clinical findings and a positive urine culture for bacteria. Blood culture results were available in 85% (28/33) of women with acute pyelonephritis. Plasma concentrations of syndecan-1 were determined by a validated immunoassay. <b>(</b>1) Women with an uncomplicated pregnancy had a higher plasma concentration of syndecan-1 than non-pregnant women. The geometric mean (95% confidence interval [CI]) of syndecan-1 concentration was 51.0 (12.1–216.1) ng/mL in non-pregnant controls; 1280 (365–4487) ng/mL in normal preterm gestations; and 1786 (546–5834) ng/mL in normal term gestations (adjusted <i>p</i> &lt; .005 for all three between group comparisons); <b>(</b>2) plasma syndecan-1 concentrations increased with gestational age among women with a normal pregnancy (<i>p</i> &lt; .001, <i>R</i><sup>2</sup> = 0.27); (3) syndecan-1 multiple of the mean (MoM) values in pregnant patients with acute pyelonephritis were higher than those in normal pregnant women based on second- and third-trimester samples (<i>p</i> = .048, 1.26-fold change). The increase was driven primarily by cases with a positive blood culture (<i>p</i> = .009, 1.74-fold change); (4) when data from third-trimester samples were compared, overall differences in syndecan-1 MoM values between cases and controls were slightly larger (<i>p</i> = .03, 1.36- fold change), which were especially contributed to by cases with a positive blood culture (<i>p</i> = .023, fold change 1.79-fold change). Plasma syndecan-1 concentration is higher in pregnant women and increases as a function of gestational age. Patients with acute pyelonephritis have a higher plasma concentration of syndecan-1, and this is particularly the case in the presence of bacteremia.