Acute kidney injury following cardiac surgery is one of the most feared postoperative complications, affecting up to 30% of patients and dramatically increasing mortality, dialysis risk, and hospital costs. A new strategy involving a single pre-operative pharmacological intervention could meaningfully shift how surgeons and anesthesiologists protect the kidneys during high-stakes procedures.
This randomized, placebo-controlled trial published in JAMA evaluated dapagliflozin — an SGLT2 inhibitor originally developed for type 2 diabetes and heart failure — administered one day before elective cardiac surgery. The primary outcome was the incidence of acute kidney injury within seven days post-operation. By testing a tight, single-day dosing window rather than chronic pre-treatment, investigators isolated the acute renoprotective effect of the drug independent of its established metabolic and cardiovascular benefits. The trial enrolled adult patients scheduled for elective cardiac procedures, making the findings directly applicable to a well-defined surgical population.
SGLT2 inhibitors have attracted significant scientific interest beyond glucose control. Their mechanism — blocking sodium-glucose cotransporter 2 in the proximal tubule — reduces tubular oxygen demand and activates cardioprotective signaling pathways that may simultaneously shield renal tissue from ischemia-reperfusion injury, the dominant mechanism underlying surgery-induced AKI. Prior observational data and sub-analyses from large cardiovascular trials (DAPA-HF, EMPEROR-Reduced) hinted at kidney-protective effects, but dedicated perioperative RCT data have been sparse.
Several important caveats apply. The elective-surgery population may not generalize to emergency or off-pump procedures. SGLT2 inhibitors carry a recognized risk of euglycemic ketoacidosis, a concern that intensifies in fasting surgical patients, so perioperative protocols would require careful glycemic monitoring. This trial represents a meaningful advance — potentially paradigm-shifting for perioperative nephroprotection — but replication across surgical centers and patient subgroups will be essential before broad adoption is warranted.