Background: Several clinical trials showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against chronic kidney disease (CKD) in both patients with and those without type 2 diabetes mellitus. Since one of the renoprotective mechanisms of SGLT2 inhibitors is thought to be amelioration of glomerular hyperfiltration, we hypothesized that an enlarged glomerular diameter, which suggests increased single-nephron glomerular filtration rate, is associated with a reduction in urinary protein after treatment with an SGLT2 inhibitor.
Methods: This study was a retrospective multicentered study including 28 adult patients with CKD who underwent kidney biopsy and were then treated with dapagliflozin, an SGLT2 inhibitor. The association of glomerular diameter with changes in urinary protein 4-8 weeks after the initiation of treatment with dapagliflozin was investigated.
Results: Maximum glomerular diameter was significantly and positively correlated with change in urinary protein-to-creatinine ratio (UPCR) (R2 = 0.44; P < 0.001). 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 (219.4 ± 23.9 vs. 188.0 ± 29.0; P = 0.005). After adjustment of age, sex and estimated glomerular filtration rate, maximum glomerular diameter was independently associated with change in UPCR (β = 0.645, P < 0.001). Furthermore, maximum glomerular diameter was independently associated with ≥ 30% reduction in UPCR (odds ratio: 1.07, 95% confidential interval: 1.01-1.14).
Conclusion: Glomerular diameter is independently associated with an early change in UPCR after the initiation of treatment with dapagliflozin in patients with CKD.
Keywords: CKD; Glomerular hyperfiltration; Glomerulonephritis; SGLT2 inhibitor.
© 2025. The Author(s), under exclusive licence to Japanese Society of Nephrology.