Prevention and treatment of acute kidney injury (AKI) in patients undergoing cardiac surgery or heart/lung transplantation

Background: Cardiac surgery and heart/lung transplantation are established treatments for various serious heart/lung conditions. Acute kidney injury (AKI) is a common complication with increased morbidity, mortality, hospital length of stay and costs.The pathophysiology behind clinical AKI is poorly studied and understood. No established strategies for the prevention/treatment of AKI after cardiac surgery exist.

Recently we showed that renal tubular injury occurs early after start of cardio-pulmonary bypass (CPB) caused by impaired renal oxygenation, as assessed by the renal vein thermodilution technique. We have also shown that the inodilator levosimendan and atrial natriuretic peptide (h-ANP) exert beneficial effects on renal perfusion and function in these patients.

Aims: The following questions will be addressed: 1) Is it possible to improve renal oxygenation during CPB and thereby renal outcome by increasing CPB flow rate? 2) Is it possible that a colloid solution in the priming fluid of the CPB circuit attenuates AKI? 3) Could the preventive treatment with h-ANP attenuate the development of AKI after heart transplantation? 4) What are the renal effects of levosimendan in postcardiac surgery patients with AKI?

Work plan: 1) During cardiac surgery, the CPB flow rate will be randomly altered (2.4, 2.7 and 3.0 L/min/m2). Measurements of renal perfusion, oxygenation and function will be performed. 2) In a Swedish multicenter, double-blinded randomized controlled trial, we aim to study the effects of a colloid-based (dextran-40) vs a conventional crystalloid-based prime on renal outcome in patients with high risk for AKI after cardiac surgery. 3) In patients undergoing heart transplantation, h-ANP or placebo will be infused during and for five days postoperatively to evaluate whether h-ANP can enhance renal recovery (measured GFR) and decrease the incidence of AKI. 4)Thirty patients with postoperative surgical AKI will be randomised to receive treatment with either placebo or levosimendan (0.1 µg/kg/min/) for 180 minutes. Renal perfusion, oxygenation and function will be measured.

Importance: Clinical AKI in cardiac surgery is devastating complication. To understand the pathophysiology and to evaluate various strategies for treatment or prevention of AKI, we may improve the outcome of these patients. The continuous renal vein thermodilution technique give us unique possibilities to answer many clinically important questions in this respect.