Ischemia-reperfusion (I/R) injury is associated with activation of coagulation and
inflammation. Interestingly, various
anticoagulants have been shown to reduce both coagulation and
inflammation in animal models of kidney I/R injury.
Fondaparinux is a synthetic pentasaccharide that selectively inhibits
factor Xa (FXa) in the coagulation cascade. The aim of this study was to investigate the effect of
fondaparinux in a lethal murine model of kidney I/R injury. A murine model of kidney I/R was established. In this model, we measured activation of the coagulation cascade and induction of
inflammation. Administration of
fondaparinux to I/R-injured mice reduced
fibrin deposition in the kidney, reduced serum
creatinine levels and increased survival from 0 to 44% compared with saline-treated control mice.
Fondaparinux also reduced
interleukin-6 and macrophage inflammatory protein-2 expression and decreased neutrophil accumulation in the injured kidneys. Finally, we showed that
fondaparinux reduced thioglycollate-induced recruitment of neutrophils into the peritoneum and inhibited the binding of U937 cells to
P-selectin in vitro. Our data suggest that
fondaparinux reduces kidney I/R injury primarily by inhibiting the recruitment of neutrophils.