In heart failure patients, is ARNI and SGLT-2 inhibitor use protective against contrast-associated acute kidney injury?

Background Heart failure (HF) patients often require contrast-based diagnostic and interventional procedures, yet they remain particularly susceptible to contrast-associated acute kidney injury (CA-AKI), a complication linked to longer hospital stay and adverse outcomes. While periprocedural IV hydration and contrast minimization are standard preventive measures, data are sparse on whether contemporary HF therapies - angiotensin receptor-neprilysin inhibitor (ARNI) and SGLT-2 inhibitors - are associated with CA-AKI risk when patients undergo contrast exposure. Aims To investigate the association of ARNI, SGLT-2 inhibitors, and their combination with CA-AKI in HF patients undergoing iodinated contrast procedures. Methods In a retrospective, single-centre cohort, we analysed 706 HF patients (HFrEF/HFmrEF/HFpEF) exposed to iodinated contrast between 2020 and 2024 via coronary angiography/PCI or contrast-enhanced CT. Pre-procedural exposure was defined as >=30 days of ARNI and/or SGLT-2 inhibitor use before the index procedure, yielding four groups: control (neither), ARNI only, SGLT-2 inhibitor only, and combined ARNI+SGLT-2 inhibitor therapy. CA-AKI was defined per ESUR as a creatinine increase >0.3 mg/dL or >1.5x baseline within 48-72 h after contrast administration. Multivariable logistic regression assessed independent associations, incorporating procedural factors (contrast volume, pre-procedural IV hydration) and clinical/laboratory covariates. Results CA-AKI occurred in 127/706 patients (18%). Those developing CA-AKI received higher contrast volumes (149+/-60 vs 98+/-42 mL; p<0.001) and had higher age and baseline creatinine. Crude CA-AKI rates were 23.5% in controls, 16.4% with ARNI only, 15.7% with SGLT-2 inhibitor only, and 15.7% with combined therapy (overall p=0.123). After adjustment, combined ARNI+SGLT-2 inhibitor therapy was independently associated with markedly lower CA-AKI odds (OR 0.366, 95% CI 0.168-0.799; p=0.012), whereas ARNI alone (OR 0.548; p=0.127) and SGLT-2 inhibitor alone (OR 0.782; p=0.423) were not independently associated. Pre-procedural IV hydration remained an independent protective factor (OR 0.381; p=0.017). Independent risk factors included diabetes (OR 1.963; p=0.015), diuretic use (OR 2.264; p=0.003), greater contrast volume (OR 1.022 per 1 mL; p=0.001), higher uric acid (OR 1.140; p=0.047), and higher CRP (OR 1.008; p=0.029), supporting internal consistency of the model. Conclusion In a real-world HF cohort undergoing iodinated contrast procedures, a protective association with CA-AKI was observed only for combined ARNI+SGLT-2 inhibitor therapy - not for either drug class alone - in addition to the expected benefit of IV hydration. These hypothesis-generating findings support prospective validation and may inform future guidance on periprocedural GDMT management in HF.