Dapagliflozin and acute kidney injury after cardiac surgery
Estimates of the proportion of people who develop acute kidney injury (AKI) after cardiac surgery range from 2% to 50%. The pathophysiology of post-operative AKI is complex and multifactorial, and, to date, no therapies have been identified that reduce its incidence after cardiac surgery.
Sodium–glucose cotransporter 2 (SGLT) inhibitors, such as dapagliflozin, are widely used in the treatment of type 2 diabetes, heart failure and chronic kidney disease. In addition to their established clinical benefits, SGLT2 inhibitors have attracted interest for their potential to prevent AKI, particularly in high-risk settings such as cardiac surgery. Potential mechanisms include lowering glomerular pressure and workload, preserving kidney perfusion, reducing hypoxia, and exerting anti-inflammatory and haemodynamic effects.
MERCURI-2 was a multicentre, double-blind, placebo-controlled superiority trial conducted at seven hospitals in the Netherlands. It evaluated whether dapagliflozin, initiated one day before elective cardiac surgery, reduced the incidence of AKI over the 7 days following surgery compared with placebo.
Adult participants were randomised in a 1:1 ratio to receive dapagliflozin (n=392) or placebo (n=392), with stratification by sex, type 2 diabetes and study site. Those assigned to dapagliflozin received 10 mg orally once daily for four doses: on the afternoon or evening before surgery, the morning of surgery, and the first and second post-operative days. Placebo was administered according to the same schedule.
Of the 784 participants, 778 (99%) completed follow-up testing (median age, 68 years; 76% male; 97% White; median BMI, 27 kg/m2; median eGFR, 80 mL/min/1.73 m2; 12% had type 2 diabetes; and 6% had heart failure).
The primary outcome, incidence of AKI (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) up to 7 days after cardiac surgery, occurred in 111 participants in the dapagliflozin group (28%) and 205 participants in the placebo group (52%) (relative risk [RR], 0.54 [95% CI, 0.45–0.65; P<0.001]). After adjustment for sex, dapagliflozin remained associated with a lower incidence of AKI. No evidence of treatment-effect heterogeneity according to sex was observed.
There was a significant difference between groups in the post-operative maximum change in eGFR from baseline, with a median change of −7.4 mL/min/1.73 m2 in the dapagliflozin group compared with −1.75 mL/min/1.73 m2 in placebo group (median difference, 4.39 [95% CI, 2.98–5.82; P<0.001]). The most frequent adverse events were incidence of atrial fibrillation (45% [176/392] in both groups) and reoperation (11% [43/392] in the dapagliflozin group versus 10% [39/392] in the placebo group). No improvements to other secondary outcomes were recorded.
The finding that dapagliflozin reduced the incidence of AKI during the first 7 days after elective cardiac surgery has important implications for perioperative care. If confirmed in further studies, integrating this simple, low-cost intervention into clinical practice could help mitigate the risk of post-operative kidney injury.
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