Background: In patients undergoing cardiac surgery with CPB, pre-existing CKD confers substantial risk for the development of cardiac surgery-associated acute kidney injury (CSA-AKI). CSA-AKI occurs in ≥50% of patients with CKD undergoing cardiac surgery with CPB vs ~20–25% of patients without CKD1,2. Causes of CSA-AKI are multifactorial and complex. There are no approved therapies that reduce the risk of AKI after cardiac surgery with CPB3. Studies suggest that damage and inflammation caused by IRI and CPB are amplified by complement activation3; early treatment with C5 inhibitors before onset of ischaemia, may lower this risk. Methods: ARTEMIS (NCT05746559) is a Phase 3, randomised, double-blind, placebo-controlled, study of ravulizumab in adults with CKD and stable cardiac disease undergoing non-emergent cardiac surgery with CPB, to reduce the risk of post-operative AKI and subsequent Major Adverse Kidney Events (MAKE) 90 days post-surgery. It consists of a screening period, randomisation and dosing 1–7 days prior to surgery with CPB (Day 1), a 90-day primary evaluation period, and survival follow-up day 365 post-CPB. Approx 736 participants will be randomised 1:1 to receive a single weight-based dose of ravulizumab or placebo; randomisation will be based on baseline CKD stage and surgery type. Primary objective: assess the efficacy of ravulizumab in reducing the risk of MAKE90, defined as meeting ≥1 of the following by day 90 post-CPB: ≥25% sustained decrease from baseline in estimated glomerular filtration rate; initiation of kidney replacement therapy; death from any cause. Safety will also be evaluated. Results: Final analysis will be conducted when all participants have completed the primary evaluation period. Conclusions: This study aims to assess whether terminal complement inhibition with ravulizumab is safe and effective in reducing MAKE and improving outcomes in patients with CKD undergoing cardiac surgery with CPB.