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

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.