Cardiovascular Effects of SGLT2 Inhibitors in Hemodialysis Patients: A Phase 2 Randomized Study

This is a Phase 2, prospective, randomized, open-label, controlled study designed to assess the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis. Despite advances in renal replacement therapy, cardiovascular mortality remains the leading cause of death in this population, often due to heart failure with preserved ejection fraction (HFpEF), arrhythmic events, and myocardial fibrosis. Preclinical models and clinical data in non-dialysis populations suggest that SGLT2 inhibitors exert antifibrotic, anti-inflammatory, and mitochondrial-stabilizing effects that may ameliorate these pathophysiological processes. A total of 80 eligible patients, aged 18-70 years and receiving online hemodiafiltration for at least 3 months, will be enrolled at Fresenius Medical Center - CEMIC Saavedra (Buenos Aires, Argentina). Participants will be randomized into two parallel groups (intervention vs. control) stratified by age, sex, and dialysis vintage. The intervention group will receive a once-daily SGLT2 inhibitor, while the control group will continue standard care. Primary outcomes include the incidence and severity of intradialytic hypotension (defined by KDOQI 2020 and HEMO criteria), longitudinal changes in left ventricular mass index (LVMI), ejection fraction, myocardial fibrosis as assessed by cardiac MRI (T1/T2 mapping), and circulating pro-fibrotic biomarkers (e.g., FGF23, procollagen types I and III). Secondary endpoints include major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and cause-specific hospitalizations. Comprehensive phenotyping will be conducted at baseline, months 3, 6, and 12. Assessments include echocardiography, cardiac MRI, 24-hour Holter monitoring, impedance cardiography, pulse wave velocity measurement, and detailed laboratory profiling. Data will be analyzed using appropriate parametric and non-parametric statistical tests, with multivariate regression and survival analysis techniques applied where relevant. The study complies with ICH-GCP guidelines and the Declaration of Helsinki. The CEMIC institutional review board has granted ethical approval. Informed consent will be obtained from all participants prior to enrollment. The study is funded by institutional and investigator resources, with biomarker assays supported by the lead investigator through his research affiliations with CEMIC and Charité -Universitätsmedizin Berlin. This study aims to address a critical unmet need in cardio-renal medicine and may lay the groundwork for future therapeutic strategies in dialysis-dependent patients.