Major clinical problem
Every year, around 14,500 heart operations are performed in the Netherlands. Up to half of these patients develop acute kidney injury after surgery. Although kidney function usually recovers, these patients face an increased long-term risk of chronic kidney disease and higher mortality. Until now, no effective drug strategy had been identified to prevent AKI in this setting. “Acute kidney injury after cardiac surgery is far from a rare complication. It affects a substantial proportion of our patients and has serious consequences later in life,” says first author Marjella Oosterom‑Eijmael. “We urgently needed a safe and simple intervention to reduce this risk.”
MERCURI-2 trial
The MERCURI-2 study is a multicenter, double-blind, placebo-controlled randomized clinical trial conducted at two academic medical centers and five non-academic hospitals in the Netherlands. Adults scheduled for elective cardiac surgery were randomized 1:1 to receive dapagliflozin 10 mg once daily or placebo. Treatment started one day before surgery and continued through the second postoperative day, for a total of four doses. A total of 784 participants were enrolled, 778 patients completed follow-up.
Striking risk reduction
The primary outcome was the incidence of AKI in the first seven days after surgery, defined according to KDIGO criteria (increase in serum creatinine or reduced urine output). Dapagliflozin reduced the incidence of AKI from 52% in the placebo group to 28% in the treatment group. “Seeing such a clear and clinically meaningful risk reduction with only four doses around surgery is remarkable,” notes first author Bram Hulst. “These results suggest we can protect the kidneys at a very vulnerable moment, without complex protocols or prolonged treatment.”
New role for SGLT2 inhibitors
SGLT2 inhibitors such as dapagliflozin are already widely used in the treatment of diabetes, heart failure and chronic kidney disease. MERCURI-2 now provides robust evidence for an additional indication: prevention of acute kidney injury after elective cardiac surgery. “Our findings expand the therapeutic potential of SGLT2 inhibitors,” explains Hulst. “We are no longer only treating existing heart or kidney disease; we can actually prevent kidney damage in the operating room.”
Impact and next steps
The MERCURI-2 results have important implications for perioperative care pathways. Introducing a short, standardized dapagliflozin regimen before and after elective cardiac surgery could reduce postoperative complications, improve long-term kidney outcomes and lower healthcare costs. “This study shows that a simple, low-cost intervention can make a real difference for thousands of patients each year,” concludes Oosterom‑Eijmael. “The next step is to work with national and international partners to integrate these findings into clinical guidelines and daily practice.”
These findings were published in JAMA. The project was funded by a grant from ZonMw.