Glomerular Diameter Is Associated with Reduction in Urinary Protein during Treatment with Dapagliflozin, a SGLT2 Inhibitor, in Patients with CKD

Background: Several clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against chronic kidney disease (CKD) complicated with or not complicated with type 2 diabetes mellitus (DM). Since one of the renoprotective mechanisms by SGLT2 inhibitors is supposed to reduce glomerular hyperfiltration, we hypothesized that glomerular diameter, which can represent abnormal glomerular hemodynamics, is associated with reduction in urinary protein after the initiation of treatment with SGLT2 inhibitors. Methods: This study was a retrospective multicentered study using 26 adult patients with CKD (mean age: 50±14 years) who underwent kidney biopsy and were then treated with dapagliflozin, an SGLT2 inhibitor, during the period between April 2019 to March 2024 in Sapporo Medical University Hospital and Steel Memorial Muroran Hospital. The association of glomerular diameter with changes in urinary protein before and 4-8 weeks after the initiation of treatment with dapagliflozin were investigated. Results: Levels of median estimated glomerular filtration rate and urinary protein at baseline were 53 [interquartile range: 32.3-69.9] mL/min/1.73m2 and 1.5 [0.69-2.84] g/gCre, respectively. Prevalences of DM and use of renin-angiotensin-system blockers were 15% and 88.4%, respectively. Maximum glomerular diameter was significantly and positively correlated with change (before – after) in urinary protein-to-creatinine ratio (UPCR) (R2=0.40; p<0.001; Figure 1A). Maximum glomerular diameter was significantly larger in patients who achieved ≥30% reduction in UPCR after the initiation of treatment with dapagliflozin than in patients who achieved <30% reduction in UPCR (220 [215, 231] vs. 185 [172-218], p=0.007; Figure 1B). Conclusion: Glomerular diameter is associated with reduction in urinary protein after the initiation of treatment with dapagliflozin in patients with CKD.