proMoting Effective Renoprotection in Cardiac sURgery patients by Inhibition of SGLT2 (MERCURI-2): A Randomized Controlled Trial in People Undergoing Cardiac Surgery

Background: Cardiac surgery can result in acute kidney injury (AKI) in up to 50% of patients, while preventative measures are largely lacking. In large kidney and cardiovascular outcome trials, sodium-glucose cotransporter-2 (SGLT2) inhibitors were associated with lower incidence of AKI (hazard ratio 0.66, 95% confidence interval (CI) 0.55-0.80). We hypothesized that perioperative treatment with the SGLT2 inhibitor dapagliflozin could reduce the incidence of postoperative AKI in patients undergoing cardiac surgery. Methods: In this multicenter, triple-blinded, placebo-controlled randomized trial, adult participants undergoing elective cardiac surgery were randomized to receive dapagliflozin (10mg orally), or matching placebo, once daily, from the preoperative day until the second postoperative day (4 doses). The primary outcome was the between-group difference in AKI incidence according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included differences in individual AKI stages. Results: Between June 2023 and May 2025, 784 patients were included (sex: 76% men, age: 67 ± 10 years, BMI: 27.2 ± 4.1 kg/m2, type 2 diabetes present in 12%) in the intention-to-treat analysis. Dapagliflozin significantly reduced the incidence of AKI (28% vs 53%; absolute difference 25%, 95% CI, -31.6 - -18.36; P < .001, Figure 1). Stage 1, 2 and 3 AKI were diagnosed in 89 (23%), 16 (4%) patients and 3 (0.8%) patients, respectively, in the dapagliflozin group, and in 156 (40%), 49 (13%), 1 (0.3%) patient(s), respectively, in the placebo group (P <.001, <.001, 0.317, respectively). Conclusion: This large multicenter trial confirmed that perioperative SGLT2 inhibition can prevent cardiac surgery-associated AKI. Funding: Government Support – Non-U.S.