Dapagliflozin Reduces Ambulatory Arterial Stiffness Index in CKD Patients with and Without Diabetes Independently of Blood Pressure Control: Results from the GLUcose Transport and Renal PROtection in Chronic Kidney Disease (GLUTREPRO) Trial

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) confer cardiovascular and renal protection, but their impact on blood pressure (BP) and vascular stiffness in chronic kidney disease (CKD) is not fully defined. AIM: To investigate the effect of dapagliflozin on 24h-BP behavior and ambulatory arterial stiffness index (AASI) as a predefined secondary outcome of the GLUTREPRO trial. METHODS: In this randomized trial, 32 patients with albuminuric CKD received dapagliflozin 10 mg/day or placebo on top of optimized standard therapy. Laboratory tests, ambulatory blood pressure monitoring (ABPM), and bioimpedance were performed at baseline and during follow-up. The study comprised a 6-month randomized phase and a 12-month open-label phase, analyzed with mixed-effects models. RESULTS: ) followed by stabilization. Overall, UACR did not change significantly, but patients with baseline microalbuminuria showed lower UACR after six months versus placebo. ABPM revealed no significant differences in BP or dipping status. Conversely, dapagliflozin significantly reduced AASI at 6 months (0.50 vs. 0.62; p = 0.04), with a trend toward sustained improvement thereafter. Multivariable regression identified dapagliflozin as an independent predictor of lower AASI (β = - 0.067; 95% CI -0.130 to -0.002; p = 0.043), independent of diabetes, 24-h Systolic BP, heart rate, kidney function, fractional sodium excretion, and TyG index. CONCLUSION: In patients with albuminuric CKD, dapagliflozin lowered AASI independently of BP control and sodium handling, suggesting favorable vascular remodeling in both diabetic and non-diabetic patients. TRIAL REGISTRATION: The study was registered in the EU Clinical Trials Register (EudraCT: 2020-004835-26) and online at the https://www. CLINICALTRIALS: gov (Unique identifier: NCT05998837, 13th April 2021).