Additive Renoprotection of SGLT2 Inhibitors and ACEi/ARBs Against Contrast-Induced Nephropathy in PCI: A Prospective Observational Study

Objective: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have renoprotective effects; however, data on chronic SGLT2i therapy for CIN prevention, particularly when combined with renin–angiotensin system (RAS) blockade, remain limited.
Methods: This prospective cohort study included 249 patients undergoing PCI between August 2024 and December 2025, comprising 126 SGLT2i users and 123 non-users. Low-osmolar non-ionic contrast media were used during the procedures. CIN was defined as an increase in serum creatinine of ≥0.5 mg/dL or ≥25% from baseline within 48 hours of contrast exposure, potentially missing cases with later peaks. Given the occurrence of only 29 CIN events, predictors were identified using Firth’s penalized regression. Sensitivity analyses were performed using inverse probability of treatment weighting (IPTW) and the KDIGO acute kidney injury criteria. The interaction between SGLT2i and ACEi/ARB use was tested using penalized regression for CIN and factorial analysis of variance for ΔCr and ΔeGFR.
Results: Despite higher rates of diabetes and heart failure among SGLT2i users, the incidence of CIN was lower in this group (7.1% vs. 16.3%, p=0.025), with smaller increases in ΔCr (0.05 vs. 0.08 mg/dL, p<0.001) and smaller declines in ΔeGFR (−3.30 vs. −5.20 mL/min/1.73 m², p=0.009). Penalized regression confirmed independent protective associations for SGLT2i use (OR 0.39, 95% CI 0.16–0.91) and ACEi/ARB use (OR 0.17, 95% CI 0.06–0.41). IPTW yielded consistent estimates (OR 0.30 and 0.12, respectively), with all standardized mean differences <0.05. The results were robust when the KDIGO criteria were applied, and the protective effects were most pronounced in patients with chronic kidney disease (CKD). The greater effect associated with ACEi/ARB use may have been related to hydration volumes of 16.9–17.6 mL/kg, which are within a beneficial range.
Conclusion: Chronic SGLT2i therapy was associated with a lower incidence of CIN and attenuated renal function decline after PCI. Concomitant ACEi/ARB use provided additive and independent protection, particularly in patients with CKD. These findings support the continuation of SGLT2i therapy during contrast exposure; however, randomized controlled trials are required to establish causality because of the observational design and small number of events.

Keywords: ACE inhibitors, contrast-induced nephropathy, percutaneous coronary intervention, renoprotection, SGLT2 inhibitors.