Depot-Specific Cardiorenal Adipose Remodeling with SGLT2i in Chronic Kidney Disease

Background and hypothesis. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) provide consistent cardiorenal benefits; however, tissue-level mechanisms remain insufficiently characterized. We investigated whether SGLT2i were associated with longitudinal remodeling of organ-specific adipose depots in patients with chronic kidney disease (CKD). Methods. In this observational study cohort (ADIPO-CKD; NCT07309094), adults with CKD stages 1–4 underwent clinical, biochemical and ultrasound imaging assessment at baseline (T0) and 8-month follow-up (T8). Thus, epicardial (EAT) and perirenal adipose tissue (PRAT) thickness were measured. Changes over time between patients under SGLT2i treatment and those without (Non-SGLT2i) were assessed using repeated-measures ANOVA and multivariable linear regression models adjusted for age, sex, baseline eGFR, diabetes status, concomitant GLP-1 receptor agonist therapy, BMI and visceral fat area (VFA) changes. Results. Among 189 CKD patients (50 SGLT2i and 139 non-SGLT2i), SGLT2i therapy was associated with significant reductions in PRAT (1.28±0.70 to 0.91±0.61 cm; ΔPRAT −0.37 cm; p< 0.002) and EAT (0.57±0.27 to 0.36±0.14 cm; ΔEAT −0.21 cm; p< 0.012), whereas no significant changes were observed in the Non-SGLT2i group. In multivariable models, SGLT2i exposure remained independently associated with ΔPRAT (β=0.447; 95% CI 0.211–0.682; p< 0.001; R²=0.371) and ΔEAT (β=0.061; 95% CI 0.009–0.113; p< 0.021; R²=0.053), including adjustment for changes in BMI and VFA. These results were accompanied by reductions in renal function and systemic inflammation biomarkers in the SGLT2i group. In a secondary analysis, dapagliflozin was significantly associated with PRAT reduction, whereas a significant association was found between empagliflozin and EAT decrease. Conclusion. In CKD stages 1–4, SGLT2i use was independently associated with decrease of EAT and PRAT. These findings are consistent with the concept of a cardiorenal adipose axis, in which organ-specific adipose modulation may contribute to metabolic and cardiorenal benefits associated with SGLT2i. Dedicated mechanistic and adequately powered comparative studies are warranted to further elucidate these associations.