Figure 1.

Schematic diagram depicting pathways leading to cardiovascular surgery-associated acute kidney injury (CSA-AKI) and role of GSK3β in the pathogenesis. There are multiple, complicated pathways mediating CSA-AKI. Cardiovascular surgery is a state of low blood flow, there is hypothermia, blood loss, activation of renin angiotensin aldosterone system (RAAS). Additionally due to CPB there is hemolysis, systemic inflammatory response syndrome (SIRS) and microemboli formation. Together these lead to reduced renal perfusion, ischemia, increase in oxidative and inflammatory injury, which in turn overactivate GSK3β. GSK3β increases proinflammatory NFκB activation, potentiates mitochondrial dysfunction as well as impairs Nrf2 antioxidant response, culminating in CSA-AKI. As an FDA-approved mood stabilizer, lithium is a standard and effective inhibitor of GSK3β and is able to ameliorate diverse types of AKI in pre-clinical models. Its efficacy in preventing CSA-AKI will be tested by this prospective, randomized, double blinded, placebo-controlled pilot clinical trial.