This double-blind, randomized controlled trial from a tertiary teaching hospital in Sweden aimed to evaluate the impact of hyperosmolar priming solutions on cardiac surgery-associated acute kidney injury (CSA-AKI). Including patients aged ≥65 years undergoing routine cardiac surgery with cardiopulmonary bypass, the study compared the effects of a Ringer’s acetate based solution with Mannitol and sodium concentrate to a control group. Results indicated that while the hyperosmolar prime solution itself did not increase postoperative CSA-AKI incidence, high plasma osmolality was identified as an independent risk factor, increasing CSA-AKI risk by 30%. The findings underscore the need for further investigation into plasma hyperosmolality’s role in CSA-AKI risk.