SGLT2 Inhibitors Mitigate Contrast-Induced Acute Kidney Injury in Diabetes: Clinical and Experimental Evidence

Contrast-induced acute kidney injury (CIAKI) is a common complication after percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (T2DM). The protective role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) against CIAKI remains unclear. We aimed to evaluate the effects of SGLT2i using nationwide database analysis and experimental models. A nationwide nested case-control study using Taiwan's National Health Insurance Research Database assessed the association between SGLT2i use and risk of post-PCI dialysis. Parallel in vitro experiments examined dapagliflozin in iopamidol-treated HK-2 cells, and in vivo studies tested dapagliflozin in diabetic rats exposed to iopamidol. Clinically, SGLT2i use significantly reduced the risk of post-PCI dialysis (adjusted OR 0.33, 95% CI 0.14-0.76; <i>p</i> = 0.0094). In vitro, dapagliflozin attenuated iopamidol-induced cytotoxicity and NLRP3 inflammasome activation in HK-2 cells. In diabetic rats, dapagliflozin improved renal function, reduced tubular injury, and suppressed inflammasome-driven inflammation. In conclusion, SGLT2i protect against CIAKI by mitigating tubular injury and inflammasome activation. These findings highlight their potential as a preventive strategy for CIAKI in T2DM patients undergoing PCI.