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 estimated glomerular filtration rate (eGFR), diabetes status, concomitant glucagon-like peptide 1 (GLP-1) receptor agonist therapy, body mass index (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 findings were accompanied by trends toward improvement in renal function and systemic inflammation biomarkers in the SGLT2i group, although these changes did not reach statistical significance. In a secondary analysis, dapagliflozin was significantly associated with PRAT reduction, whereas a significant association was found between empagliflozin and EAT decrease. Conclusions: In CKD stages 1–4, SGLT2i use was independently associated with reductions in EAT and PRAT. These findings support a potential link between organ-specific adipose tissue and cardiorenal disease; however, given the observational design, these results should be interpreted as associative and hypothesis-generating. Dedicated mechanistic and adequately powered studies are warranted to determine their clinical relevance.

Metabolic syndrome (MetS) drives cardiac remodeling and fibrosis, contributing to diastolic dysfunction and heart failure with preserved ejection fraction, but chamber-specific mechanisms remain poorly defined. New Zealand White rabbits were fed a high-fat/high-sucrose diet for 28 weeks to induce experimental MetS. Systemic phenotype, cardiac structure (echocardiography), myocardial fibrosis (Picrosirius red histology), myosin/collagen gene expression (qRT-PCR), and chamber-specific proteomics were assessed across left/right atria and ventricles. The model reproduced central obesity, glucose intolerance, dyslipidemia, and mild hypertension, with concentric left ventricular hypertrophy and selective ventricular fibrosis, as follows: increased collagen in left ventricle (LV) and right ventricle (RV), unchanged in atria. Ventricular α-myosin heavy-chain gene expression was upregulated, while collagen I and α-smooth muscle actin transcripts showed ventricular-specific downregulation. Proteomics revealed atrial metabolic and cytoskeletal adaptations with minimal extracellular matrix involvement; ventricles displayed early profibrotic cues (galectin-3 in LV), metabolic inefficiency (impaired glycolysis/ATP production in LV; lipid oxidation shift in RV), and diminished provisional matrix support. Conclusions: concentric LV hypertrophy and great vessel enlargement occurred without systolic/diastolic dysfunction; ventricular-selective fibrosis, α-myosin heavy-chain upregulation, type I collagen/α-smooth muscle actin downregulation, and chamber-specific proteomic changes showed atrial adaptation versus ventricular early profibrotic/metabolic inefficiency.

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 estimated glomerular filtration rate (eGFR), diabetes status, concomitant glucagon-like peptide 1 (GLP-1) receptor agonist therapy, body mass index (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 findings were accompanied by trends toward improvement in renal function and systemic inflammation biomarkers in the SGLT2i group, although these changes did not reach statistical significance. In a secondary analysis, dapagliflozin was significantly associated with PRAT reduction, whereas a significant association was found between empagliflozin and EAT decrease. Conclusions. In CKD stages 1–4, SGLT2i use was independently associated with reductions in EAT and PRAT. These findings support a potential link between organ-specific adipose tissue and cardiorenal disease; however, given the observational design, these results should be interpreted as associative and hypothesis-generating. Dedicated mechanistic and adequately powered studies are warranted to determine their clinical relevance.