Acute kidney injury complicates a large proportion of cardiac surgery and no drug has ever been shown to prevent it. This double-blind trial at two academic and five non-academic Dutch hospitals randomised 784 adults undergoing elective cardiac surgery to dapagliflozin 10 mg orally or placebo once daily, starting the day before surgery and continuing through the second postoperative day — four doses in total. Median age was 68, 76% were men, and median estimated glomerular filtration rate was 80 mL/min/1.73 m2.
Acute kidney injury by KDIGO criteria during the first seven postoperative days occurred in 28% of the dapagliflozin group and 52% of the placebo group, relative risk 0.54 (95% CI 0.45 to 0.65, p<0.001). Adverse events did not differ: atrial fibrillation was 45% in both arms, and reoperation 11% versus 10%.
The 52% event rate in the placebo arm is the number to notice. This is a KDIGO-defined endpoint that includes a creatinine rise of 26.5 micromol/L, which captures a great deal of transient, self-limiting injury. So the benefit is real and large, but what has been halved is mostly biochemical acute kidney injury, not dialysis. The trial does not report whether renal replacement therapy, length of stay or longer-term kidney function changed.
The practical caution is the one every SGLT2 inhibitor carries. Four perioperative doses in a fasting surgical patient is exactly the situation in which euglycaemic ketoacidosis occurs, and the trial's protocol — starting the day before and continuing after — will need careful translation into units without the same monitoring. The population was also 97% White with preserved renal function at baseline.
- Consider perioperative dapagliflozin 10 mg for elective cardiac surgery, from the day before through the second postoperative day
- Read the endpoint carefully — KDIGO acute kidney injury includes transient creatinine rises, and dialysis outcomes were not reported
- Monitor for euglycaemic ketoacidosis in a fasting perioperative patient on an SGLT2 inhibitor, checking ketones rather than glucose
- Note the trial population had preserved renal function at baseline; this does not test the patient with established chronic kidney disease
- Atrial fibrillation and reoperation rates were unchanged, so there is no evident safety cost in this population
The statistics, in plain English
A relative risk of 0.54 with an interval of 0.45 to 0.65 is a large and precisely estimated effect, and the absolute difference of 24 percentage points means about four patients treated to prevent one episode — a strikingly low number. The caveat is in the endpoint's composition rather than its statistics. KDIGO acute kidney injury is triggered by a creatinine rise of 26.5 micromol/L within 48 hours or a urine output below 0.5 mL/kg/h for six hours, both of which are common and often transient after bypass. A halving of that endpoint is meaningful but is not the same as a halving of dialysis or of chronic kidney disease, neither of which this trial reports.
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