Kidney injury is a common occurrence in hospitalised patients, particularly those who are critically ill, occurring in almost two out of three patients in intensive care units. The presence of even mild kidney injury increases time spent in hospital and increases critically ill patients’ risk of dying. Even small improvements of kidney function could potentially provide significant improvements in outcome for a large number of patients.
Ischaemia/reperfusion injury (IRI) is a leading cause of kidney injury. IRI follows when blood supply to the kidney is interrupted and it occurs in a number of settings including kidney transplantation. The group has been investigating the mechanisms that cause IRI of kidneys, with the goal of discovering novel ways to prevent or treat injury.
The group has been working on the role of the protease activated coagulation system, studying its role as an arm of the innate immune inflammatory response and its role in angiogenesis. Their studies in mice have demonstrated that thrombin generated as a result of Tissue factor activity plays an important role in IRI by activation of protease activated receptor -1 (PAR-1). The group has shown that by blocking PAR-1 we can prevent injury. They have also shown that PAR-1 contributes to chronic kidney injury in a model of progressive renal fibrosis and obstruction, but here the ligand may be different as thrombin deficiency was not clearly protective.