Ciclosporin to Protect Renal Function In Cardiac Surgery

Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with decreased long-term survival. The mechanism for inducing acute kidney injury is unknown but ischaemia-reperfusion injury is indicated to be a part of the cause.

Animal studies have showed cytoprotective, preconditioning and anti-apoptotic effects of ciclosporin in ischaemia-reperfusion injury in the kidney. The major mechanism is thought to be inhibition of the reperfusion triggered opening of the mitochondrial permeability transition pore (mPTP), responsible for reperfusion-induced necrosis. During cardiac surgery, the period of extracorporeal circulation (ECC) changes the perfusion through the kidney. Return to normal perfusion with a beating heart has similarities with reperfusion following ischemia.

Administration of ciclosporin in conjunction with percutaneous coronary intervention (PCI), heart surgery and traumatic brain injury (TBI) in humans has shown to be safe with no direct side-effects.

The investigators therefore hypothesize that a preconditioning effect of ciclosporin before coronary artery bypass grafting (CABG) can reduce the level of renal dysfunction after this type of cardiac surgery.

Inclusion criteria

• Non-emergent CABG
• Written informed consent to participate
• Preoperative CyC eGFR or MDRD eGFR is 90-15.

Exclusion criteria

• Uncontrolled hypertension
• Hypersensitivity to ciclosporin or any of the excipients of the lipid emulsion, including egg-, soya- or peanut protein
• Pregnancy or fertile woman
• Ciclosporin treatment within 4 weeks
• Ongoing malignancy, ongoing immunosuppressive treatment, severe hepatic dysfunction, dialysis or severe infection
• Ongoing medication with dabigatran, aliskiren, bosentan, stiripentol, glibenclamid, St John's worth, or
• Off-pump surgery