Background: Cardiac surgery-associated acute kidney injury (CS-AKI) remains a vexing issue. Clinical trials for the prevention of CS-AKI have been disappointing despite enormous initial enthusiasm based on experimental data. 

Summary: The schism in experimental and clinical data has triggered a relook at our understanding of CS-AKI and the experimental and preclinical models. In this review, we discuss the therapeutic targets of major clinical trials. 

Key Messages: The silver lining in the midst is the standardization of anesthetic and perioperative care proposed by national societies. Implementation of the KDIGO bundle is a reasonable option to decrease the incidence of CS-AKI despite lack of proven robust benefits.