IMPORTANCE: Two percent to 50% of patients undergoing elective cardiac surgery experience acute kidney injury (AKI) postoperatively. Medications to prevent AKI after elective cardiac surgery have not been identified.
OBJECTIVE: In patients undergoing elective cardiac surgery, to evaluate whether initiating dapagliflozin 1 day prior to surgery reduces the incidence of AKI at 7 days after cardiac surgery, compared with placebo.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled randomized clinical trial conducted at 2 academic medical centers and 5 nonacademic hospitals in the Netherlands. Eligible participants were adults undergoing elective cardiac surgery. Enrollment occurred between June 8, 2023, and January 27, 2025. Final follow-up occurred May 16, 2025.
INTERVENTION: Patients were randomized 1:1 to receive either dapagliflozin (10 mg orally; n = 392) or placebo once daily (n = 392), beginning on the day before surgery and continuing through the second postoperative day (total of 4 doses).
MAIN OUTCOME AND MEASURE: The primary outcome was the between-group difference in AKI (defined as an increase in serum creatinine level by at least 0.3 mg/dL [26.5 µmol/L] within 48 hours after surgery, a 1.5-fold creatinine increase within 7 days of surgery, or urine output less than 0.5 mL/kg/h for 6 to 12 hours according to Kidney Disease: Improving Global Outcomes criteria) during the first 7 postoperative days.
RESULTS: Of 784 participants enrolled, 778 (99%) completed follow-up testing (median age, 68 [61-74] years; 76% male; 97% White; median body mass index, 27 [IQR, 25-30]; and median estimated glomerular filtration rate, 80 [IQR, 67-89] mL/min/1.73 m2). Compared with placebo, dapagliflozin reduced the incidence of AKI (28% vs 52%; relative risk, 0.54 [95% CI, 0.45-0.65]; P < .001) over 7-day follow-up after surgery. Atrial fibrillation and reoperation were the most frequent adverse events. The incidence of atrial fibrillation was 45% (176/392) in the dapagliflozin group vs 45% (176/392) in the placebo group, and the incidence of reoperation was 11% (43/392) vs 10% (39/392), respectively.
CONCLUSIONS AND RELEVANCE: In patients undergoing elective cardiac surgery, 4 doses of dapagliflozin, beginning the day before surgery, reduced the incidence of AKI during the 7-day postoperative period.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05590143.
| Discipline Area | Score |
|---|---|
| Nephrology |  |
| Cardiology |  |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Surgery - Cardiac |  |
Although the incidence of mild and moderate AKI (KDIGO stage 1 and 2) was significantly decreased, clinically relevant serious renal injury was not significantly different between groups, nor was there any change in MACE, length of stay, or more clinically relevant variables. I would hypothesize that SGLT2i had a diuretic effect perioperatively with very little clinical risk, but it remains unclear whether there is a clinically significant, patient-facing benefit to their perioperative administration in elective cardiac surgery. Further work is needed to elucidate their precise role.
Very important finding, if reproduced.
An interesting and useful outcome. Replication in cardiac and non-cardiac surgeries would help support the notion of treatment benefit.
Practice-altering information. Cardiologists and cardiac surgeons are better placed to implement this information, but it is highly relevant to nephrology practice.
Based on Table 2, the risk of AKI in the dapagliflozin group was 28/111 and in the control group was 52/205. Using these numbers, the ARR is 0.09%, and the NNT is 1,128. Given that 4 doses of dapagliflozin are not too expensive (about $80.00), it may be worth spending $90,000.00 to prevent one patient from having AKI. A 35% RR reduction is technically correct but clinically naive. This information should be in the discussion.
Good article. Although small, the incidence of fungal infection and hypoglycemia is concerning.