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. 2021 Jul;35(4):1789-1799.
doi: 10.1111/jvim.16163. Epub 2021 Jun 2.

Association of markers of endothelial activation and dysfunction with occurrence and outcome of pulmonary hemorrhage in dogs with leptospirosis

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Association of markers of endothelial activation and dysfunction with occurrence and outcome of pulmonary hemorrhage in dogs with leptospirosis

Franziska Sonderegger et al. J Vet Intern Med. 2021 Jul.

Abstract

Background: Endothelial dysfunction might contribute to the development of leptospiral pulmonary hemorrhage syndrome (LPHS).

Hypothesis: Serum concentrations of markers of endothelial activation and dysfunction are higher in dogs with leptospirosis and correlate with the occurrence of LPHS and a higher case fatality rate.

Animals: Clinically healthy dogs (n = 31; 10/31 dogs confirmed healthy based on no detected abnormalities on blood work), dogs with leptospirosis with LPHS (n = 17) and without LPHS (n = 15), dogs with acute kidney injury not due to leptospirosis (AKI-nL, n = 34).

Methods: Observational study. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2) at admission were compared between groups. Correlations with outcome and the accuracy to predict LPHS were examined.

Results: Soluble intercellular adhesion molecule (sICAM-1), VEGF, and Ang-2 concentrations were higher in dogs with AKI-nL (sICAM-1 34.7 ng/mL, interquartile range [IQR] = 24.4-75.5; VEGF 43.1 pg/mL, IQR = 12.3-79.2; Ang-2 8.5 ng/mL, IQR = 6.2-12.3), leptospirosis without LPHS (sICAM-1 45.1 ng/mL, IQR = 30.6-59.0; VEGF 32.4 pg/mL, IQR = 12.5-62.6; Ang-2 9.6 ng/mL, IQR = 6.9-19.3), and LPHS (sICAM-1 69.7 ng/mL, IQR = 42.1-89.1; VEGF 51.8 pg/mL, IQR = 26.3-96.7; Ang-2 8.0 ng/mL, IQR = 5.6-12.2) compared to controls (P < .001). In dogs with leptospirosis, VEGF and sICAM-1 were higher in nonsurvivors (sICAM-1 89.4 ng/mL, IQR = 76.5-101.0; VEGF 117.0 pg/mL, IQR = 90.3-232.4) than survivors (P = .004) and sICAM-1 predicted the development of LPHS.

Conclusions: Soluble intercellular adhesion molecule 1, VEGF, and Ang-2 do not discriminate leptospirosis from AKI-nL. In dogs with leptospirosis, sICAM-1 and VEGF predict outcome and sICAM-1 might identify dogs at risk for LPHS.

Keywords: Leptospira; acute kidney injury; bleeding; canine; endothelial marker; respiratory.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
A‐C, Day 1 serum soluble intercellular adhesion molecule (sICAM‐1; A), vascular endothelial growth factor (VEGF; B), and angiopoietin‐2 serum concentrations (Ang‐2; C) in healthy dogs and dogs with acute kidney injury due to other etiologies (AKI‐nL), leptospirosis without pulmonary hemorrhage (Lepto), and dogs with leptospiral pulmonary hemorrhage syndrome (LPHS). Median sICAM‐1, VEGF, and Ang‐2 concentrations are significantly higher in the 3 disease groups compared to healthy controls, but there is no significant difference between disease groups. The central lines in the boxes represent the median values, and the top and bottom of the boxes represent the 75th and 25th percentiles, respectively
FIGURE 2
FIGURE 2
A‐C, Day 1 serum soluble intercellular adhesion molecule (sICAM‐1; A), vascular endothelial growth factor (VEGF; B), and angiopoietin‐2 serum concentrations (Ang‐2; C) in surviving and nonsurviving dogs with leptospirosis with or without pulmonary hemorrhage. Median sICAM‐1 and VEGF serum concentrations are significantly higher in nonsurvivors compared to survivors. The central lines in the boxes represent the median values, and the top and bottom of the boxes represent the 75th and 25th percentiles, respectively

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