Prevention of coronary artery bypass surgery induced acute kidney injury

Professor Stephen Holdsworth, Monash University

2020 Vanguard Grant

Years funded: 2021-2023

Coronary artery bypass graft (CABG) surgery is one of the most common surgical operations in Australia. It is a procedure to improve poor carotid blood flow to the heart and may be needed when the arteries supplying blood to the heart are narrowed or blocked. A common complication after CABG surgery is development of acute kidney injury (AKI). AKI has also been shown to increase long term risk of end stage renal failure requiring dialysis and premature death.

Our basic research shows that our experimental ischaemic AKI model of induced ischaemia-reprefusion injury induces similar to that observed in man following CABG surgery. We found mast cells are a major inducer of acute kidney injury by degranulation which releases injurious mediators. Disodium cromoglycate (DSCG) is an allergy drug that stabilises mast cells to prevent degranulation. It is now agreed that mast cells also play a major role in innate host immunity and the induction of inflammatory injury. DSCG is a well-studied, safe anti-allergy drug that blocks the major pathway of mast cell induced injury, degranulation. We found, in mice, that prophylactic DSCG significantly reduces the incidence and severity of ischemia induced AKI.

The objectives of the grant is to confirm that DSCG used peri-operative will prevent CABG surgery associated AKI. This safe, minor intervention will significantly prevent CABG associated loss of kidney function. We aim to conduct a double-blind, placebo controlled, randomised clinical trial to assess the capacity of prophylactic DSCG to reduce the frequency of AKI in patients undergoing CABG surgery.

The expected outcomes will be reduction in the incidence and severity of ischaemic AKI in these. The expected outcomes will be reduction in the incidence and severity of ischaemic AKI in these patients. These successful outcomes will help this simple prophylactic manoeuvre become standard of care.